Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Breast Neoplasms

Pancreatic Neoplasms

Cholangiocarcinoma

Lymphoma

Liver Neoplasms

Head and Neck Neoplasms

Sarcoma

Chordoma

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Adenocarcinoma

Neoplasms, Germ Cell and Embryonal

Pancreatic Cancer

Bile Duct Cancer

Lymphosarcoma

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Pharmaceutical Solutions

Dermatologic Agents

Antibodies

Pembrolizumab

Cisplatin

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Vinblastine

Coal Tar

Immunoglobulins, Intravenous

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INT230-6 injections every 28 days for 5 sessions into only superficial tumors, low starting dose, low concentration per tumor.

Completed

INT230-6 injections every 28 days for 5 sessions into deep tumors, low starting dose, low drug concentration per tumor

Completed

INT230-6 injections every 2 weeks for 5 sessions into superficial tumors, medium starting dose, low drug concentration per tumor

Completed

INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor

Completed

INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC

Completed

INT230-6 injections every 2 weeks for 5 sessions with the possibility for INT230-6 retreatment into superficial tumors, with addition of anti-PD-1 antibody Keytruda (pembrolizumab) dosed concurrently starting at Day 1 every 3 weeks for two years for selected cancer types.

Completed

INT230-6 injections every 2 weeks for 5 sessions at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years.

Completed

INT230-6 per the dosing of cohort EC3 combined with Keytruda (pembrolizumab) dosed per DEC concurrently starting at Day 1 for selected cancers.

Completed

INT230-6 per the EC3 regimen combined with Yervoy (ipilimumab) dosed concurrently starting at Day 1 every 3 weeks for four treatments for selected cancer types.

Completed

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

INT230-6

The anti-PD-1 antibody will be added concomitantly with INT230-6 as noted in cohort DEC and DEC2

anti-PD-1 antibody

The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC

anti-CTLA-4 antibody

Ian B. Walters, M.D.

Lillian Siu, M.D., FRCP

Anthony El-Khoueiry, M.D.

Anthony J. Olszanski, M.D., RPh

Nilofer Azad, M.D.

Giles F Whalen, M.D.

Matthew Ingham, M.D.

Luis Camacho, M.D.

This study evaluates the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study is being conducted in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also plans to test INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.

INT230-6 is comprised of a 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumors and enables increased diffusion into cancer cells. (Nonclinical safety studies showed no findings following drug injection into healthy tissues.)

Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumors and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumor site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient.

Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents.

Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrates strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates.

Clinical trial IT-01 seeks to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus as part of study IT-01 the Sponsor seeks to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4 or anti-CTLA-4) receptors.

This study seeks to understand whether tumor regression can be achieved and patient outcomes improved.

There were 6 cohorts in the escalation portion of the protocol. Five dosed INT230-6 alone and one was combined with pembrolizumab. Cohorts A and B1 treated superficial tumors at a 1:4 ratio of drug to tumor with a low tumor load once per month. Cohort EA was similar to cohort A with INT230-6 every 2 weeks. Cohort EC escalated the total and maximal dose per any one tumor to a ratio of 1:2 \& dosed every two weeks. Cohort EC2 explored a drug load ratio of 1:3 and escalated the dose per tumor further. Cohort DEC combined INT230-6 with a fixed amount of pembrolizumab.

On-going, non-escalation cohorts include 1) monotherapy INT230-6 cohort (EC3) dosed every two weeks 2) INT230-6 in a combination with pembrolizumab (DEC2) and 3) INT230-6 in combination with ipilimumab (FEC). Other specific regimens or combinations of INT230-6 may be designated by the Study Steering Committee.

There is no masking and all patients will receive INT230-6 treatments.

A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6

A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers

Characterize response in non-injected lesions (up to 5) using length (cm) as the key parameter for measurement.

Evaluate various tumor and anti-tumor immune response biomarkers from blood, tumor tissue that may correlate with tumor response. Flow and tissue panels may include Live-Dead, CD3, CD4, CD8, FoxP3, Ki-67, ICOS, DAPI, PD-1, LAG-3, TIM-3, CTLA-4 and analysis of blood serum cytokine such as Th1/Th2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-13, and TNF-α.

Evaluate overall response by iRECIST including survival

The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease.

All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance.

Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose.

Assess the preliminary efficacy of INT230-6 by measuring the disease control rate (CR+PR+SD) as assessed by iRECIST.

Assess INT230-6's effect on tumors by measuring the length, width and height (centimeters) of injected tumors during the dosing and afterward.

Characterize the peak plasma profile for the three INT230-6 components after single and then multiple IT tumor site injections for safety purposes. This has been completed.

Characterize the pharmacokinetic AUC profile of each of the three INT230-6 components for AUC after single IT tumor site injection for safety purposes. This has been completed.

Characterize the half life of each of the three INT230-6 components after single and multiple IT tumor site injections for safety purposes. This has been completed.

Merck Sharp & Dohme LLC

Bristol-Myers Squibb

Intensity Therapeutics, Inc.

Symptoms and General Pathology

Skin Neoplasms

Neoplasm Metastasis

Skin Diseases

Antibodies, Monoclonal

Open label study drug 2141-V11 at escalating doses until MTD is determined, and expansion utilizing the MTD.

2141 V-11

Juan Osorio, MD, PhD

The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study drug activates a naturally occurring protein called CD40. By activating CD40, cells of the immune system are better able to identify and kill cancer cells.

We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well tolerated, and may result in immune activation in patients with solid tumors that have metastasis to the skin.

This is a Phase 1 open label, dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of the Fc-engineered variant 2141-V11 in patients with previously treated relapsed or refractory solid tumors and locally advanced or metastatic solid tumors to the skin amenable to intratumoral injection.

There are two parts to the study: a dose-finding stage (Part I), and a dose expansion stage (Part II). Both Part I and Part II of the study will include patients with locally advanced or metastatic cancers of the skin which are not amenable to standard treatment.

A traditional 3 + 3 dose escalation design will be used (Part I). Successive cohorts of participants (3 participants/cohort) will be started on a fixed dose intratumoral injection of 2141V11 at the dose assigned to their cohort. The study drug, 2141-V11, will be dosed once every 3 weeks. The study drug is administered in cycles.

The first group of study participants in Part I will receive the lowest dose of study drug. The next group of study participants will receive the next higher dose. This dosing scheme continues until the maximum tolerated dose is determined. The maximum tolerated dose (MTD) will be defined as 1 dose level below the dose in which DLTs are observed in \>33% of the participants.

Participants in Part II of the study will receive the MTD determined from Part 1 (dose escalation) of the study. Part II participants in the study will also receive two vaccinations (KLH and tetanus) to allow monitoring of their immune function.

Participants in both Part I and II can continue to receive cycles of study drug at their assigned dose if they do not experience progression of disease, a serious adverse event, and the study is ongoing.

Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of 2141-V 11 using a standard 3+3 dose-escalation design.

A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin

A Phase I, Dose-escalation Study Investigating the Safety and Tolerability of Intratumoral Injection of an Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) in Patients With Cancer

Change from baseline laboratory assessments and toxisities over time

Anti-Drug antidoby (ADA) response over time

Rockefeller University

Infections

Mouth and Tooth Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Measles

Rubella

Mumps

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Micronutrients

Hypoglycemic Agents

Bone Density Conservation Agents

Vitamins

Lidocaine

Vaccines

Insulin

Insulin, Globin Zinc

Vitamin D

Cholecalciferol

Trace Elements

Vitamin D3

Calciferol

All Group A patients will receive intralesional MMR.

All Group B patients will receive intralesional Vitamin D3

Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.

Measles-Mumps-Rubella Vaccine

Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier

Vit D

Bibisha Baaniya, MBBS

Common warts are papulonodular epidermal lesions caused by human papillomavirus (HPV) usually by the strains 1, 2, 4, 27 or 57. Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence between 12 and 16 years. There are multiple destructive treatment modalities of wart but they have many adverse effects. Hence immunotherapy is becoming popular in treatment of warts. It is believed that the injection to the HPV-infected tissue induces a strong nonspecific pro-inflammatory signal and attracts the antigen-presenting cells. Which then promotes a Th1 cytokine response and leads to delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells.

We are undertaking a study to evaluate and compare the safety and efficacy of 2 such immunotherapeutic agents namely, IL measles, mumps and rubella (MMR) vaccine versus IL vitamin D3 for the treatment of warts.

RESEARCH HYPOTHESIS Null Hypotheses: IL MMR vaccine is not better than IL Vitamin D in the treatment of wart Alternative hypothesis: IL MMR vaccine is better than IL Vitamin D in the treatment of wart

Method: A total of 60 patients will be included in the study, 30 in each group. Group A and Group B patients will be injected with 0.5 ml of IL MMR and 0.5 ml of IL vitamin D3 respectively into a single or a maximum of 5 warts at a time in case of multiple warts. The IL injection will be given every 3 weeks for a maximum of 5 doses. Clinical assessment will be done by taking photographs and measurements at baseline, before each treatment session, and 3 months after the completion of treatment. The response will be evaluated by a decrease in the size and number of the wart(s) and photographic comparison. The response will be considered complete if there is a complete clearance of the wart(s), good if the wart(s) will regress in size by 75-99%, moderate if they regress by 50-74% and no or mild if there will be a 0-49% decrease in wart(s). Immediate and late side effects of MMR and Vitamin D will be evaluated after each session. Follow up will be made monthly for 3 months to detect any recurrence. Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up.

Statistical analysis will be done using Statistical Package for the Social Sciences 10.5 version.

INTRODUCTION Warts are common skin conditions resulting from infection of keratinocytes by human papillomavirus (HPV). After infection of the basal layer, there is clonal proliferation leading to epidermal thickening and hyperkeratinization and eventually results in a visible wart. HPVs are ubiquitous, epitheliotropic non-enveloped small double-stranded DNA viruses. Over 150 types of HPVs have been identified. Among them verruca vulgaris are usually caused by HPV types 1, 2, 4, 27 or 57, and plane warts by HPV types 3 or 10.

Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence between the ages of 12 and 16 years. In children, clearance can occur after only a few months, with 50% at 1 year and about 65%-78% by 2 years. The rate of clearance is influenced by factors like virus strain, host immune status, extent and duration of warts. The transmission of warts occurs from direct contact or indirectly via fomites.

There are multiple destructive, antiproliferative and antiviral agents in treatment of warts. Other modalities include hypnotherapy, acupuncture, local hyperthermia, therapeutic vaccination and combinations of the previous agents. Destructive therapies usually come with many adverse effects hence immunotherapy is becoming more popular, especially in the treatment of refractory cutaneous and genital warts. These include various topical, intralesional (IL) and systemic agents. IL Measles, Mumps, rubella (MMR) and IL vitamin D3 are examples of immunotherapeutic agents.

Immunotherapy is defined as a type of biological therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Immunotherapy can affect the immune system in general or can be cell-specific.

Immunotherapy is believed to induce a strong nonspecific pro-inflammatory signal and attract the antigen-presenting cells. This is associated with the release of cytokines such as IL-2, IL-8, IL-12, IL-I8, tumor necrosis factor-α, and interferon-γ. This then promotes a Th1 cytokine response which leads to the activation of delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells. Furthermore, the trauma of the injection may also cause a resolution in previously sensitized individuals. Vitamin D3 is also claimed to regulate epidermal cell differentiation and proliferation and may modulate cytokine production through its action upon vitamin D receptors (VDRs). Since IL antigen immunotherapy enhances recognition of the virus by the immune system it causes clearance of both treated and untreated lesions and helps to prevent future clinical infection through induction of long-term acquired immunity to HPV.

MMR vaccine is included in immunization schedule of Nepal so pre-sensitization skin test is not needed as all patients are expected to be immune. The presence of 3 different antigens in MMR increases the sensitivity to the injected antigen and decreases the likelihood of anergy. Side effects of MMR include pain during injection, flu-like symptoms, pruritus and burning sensation.

IL vitamin D is a novel addition to therapies in warts as it is a simple, effective, well-tolerable, and inexpensive method with negligible local and systemic side effects. Side effects of Vitamin D3 include transient mild to moderate pain, edema at the site of injection and mild erythema. Additionally, it would be safer to monitor serum vitamin D and calcium levels before and after intralesional vitamin D treatment to prevent possible hypervitaminosis D.

RATIONALE Intralesional Immunotherapy is an emerging method of treatment of wart in which injection in a single wart causes the resolution of distant warts as well. Compared to other destructive modalities, it is more effective and comfortable for the patient as it obviates the need for individual treatment of each wart. In addition it has a lower rate of recurrence, avoids adverse effects such as scarring, is more cost-effective in multiple warts and decreases the time a physician has to spend on each patient. Further both injection MMR and Vitamin D3 are readily available as compared to other immunotherapeutic agents like purified protein derivative and candida antigen.

IL MMR vaccine has been used for a longer time than IL vitamin D and there are more comparative studies showing efficacy of MMR vaccine with rates of clearance ranging from 70.4% to 82.4%. The clearance rates for IL vitamin D ranges from 40% to 90%.

The advantages of vitamin D over MMR vaccine are cost-effectiveness, non-requirement of maintenance of cold chain, easy availability, and feasibility of use in immunosuppressed patients.

As per Institute of Medicine (IOM), the tolerable upper intake of vitamin D is 4000 IU/day for anyone older than 9 years such that annual maximum dose will be 1,460,000 IU. The total amount of vitamin D that we will be administering will be 1,500,000 IU. Furthermore, since we are giving it intralesionally systemic absorption is likely to be low although data on exact amount of IL vitamin D that gets absorbed systemically is not available. In other studies, patients have been evaluated clinically for signs and symptoms of hypervitaminosis D however, no signs of toxicity were observed.

As per our literature search,

1. No previous studies on immunotherapy in wart have been conducted in our country
2. No comparative studies have been done to compare IL MMR and IL vitamin D3 in treatment of wart hence we aim to establish efficacy of each and compare the two.

OBJECTIVES

Primary Objectives:

1. To determine the efficacy of IL MMR vaccine in the treatment of Wart
2. To determine the efficacy of IL vitamin D in the treatment of wart
3. To compare the efficacy of IL MMR vaccine and IL Vitamin D

Secondary Objective:

1. To determine the clinical and demographic profile of patients with different types of warts visiting Dermatology outpatient department(OPD) of BP Koirala Institute of Health Sciences (BPKIHS)
2. To determine the side effects of IL MMR vaccine and IL Vitamin D in treatment of wart
3. To determine Dermatology life quality index (DLQI) in wart patients.

Operational definition Wart - clinical diagnosis made by a dermatologist Complete response (100%)- Complete disappearance of warts including distant ones and skin texture at the site is restored to normal Excellent response (75-99%)-Reduction in size and number including distant ones and few residual warts still visible Good response (50-74%)-Some reduction in size only including that of distant ones but no decrease in number of warts Poor or no response (0-49%)-No significant change in size and number of warts Recurrence- Recurrence during the study period

MATERIALS AND METHODOLOGY Materials: Study population will be all patients clinically diagnosed with warts visiting the Dermatology OPD of BPKIHS, Dharan.

Study design: Prospective comparative longitudinal study Study Period: Probable duration of the study will be 1 year after approval from the Institutional Review Committee (IRC) and Nepal Health Research Council (NHRC) Ethical Clearance: Taken from IRC, BPKIHS and NHRC Conflict of interest: None Sampling Technique: Census method with all consecutive patients meeting inclusion criteria for initial 6 months Sample size The study considers a 95% confidence interval, 80% power to estimate sample size. According to the literature review, it was found that there was 84.6% and 40% improvement in MMR and Vitamin D respectively.

Now using the sample size estimation formula for 2 proportion {(Zα√2p(1-p)+ Z1-β√((p1(1-p1) p2(1-p2)}2))/(p1-p2)2 Where n= sample size for each group p1 = 0.846 p2 = 0.40 p= (p1 +p2)/2 Zα=1.96 Z1-β = 1.28 Using above formula, n= 12.3 The formula for actual sample size is n/4{1+√(1+4/n\|p1-p2\|)}2 na = 16.48 Adding 10% in calculated value to reduce bias sampling technique, the minimum sample size in each group is 18.13 =19 Considering loss of follow up, sample size in each group= 30 Total sample size= 60

Methodology Based on the computer generated random number table, patients satisfying inclusion criteria will be assigned to either Group A or Group B once they come to OPD. Informed consent will be taken and detailed information including personal data, past history, medical history, drug history, clinical data like site, size, number and distribution of lesions will be recorded in preset pro forma. Photographs of the lesions will be taken before the first treatment session, in every treatment session and 3 months after last session.

Group A Freeze-dried MMR vaccine single-use vials stored at 2°C-8°C will be reconstituted with 0.5 mL of distilled water immediately before IL use. If reconstituted vaccine is not used within 8 hours it must be discarded. All Group A patients will receive IL injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts with 31 G insulin syringe with beveled edge facing upward. Amount of injection on each wart will depend on the size of each wart. The injection will be given every three weeks for a maximum of 5 doses.

Group B All Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. Amount of injection on each wart will depend on the size of each wart. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier. In patients of group B serum vitamin D level will be measured after 20 days of 3rd dose and 1 month after the last dose to ensure safe monitoring.

Patient and physician global assessment using 'Visual Analog Scale score' and photographic comparison will be used to assess the response to treatment as mentioned in operational definition. Immediate and late adverse effects in both groups will be evaluated after each treatment session. Necessary investigations and intervention will be done if needed. Follow up will be made monthly for 3 months to detect any recurrence.

Quality of Life(QoL) QoL will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment. The clinically meaningful change or reduction in the DLQI score is measured as the change in score from one band to the other.

Statistical analysis

1. Data handling: Data will be entered in Microsoft Excel 2010 and statistical analysis will be done using Statistical Package for the Social Sciences 10.5 version
2. Coding: Alpha numerical code will be used
3. Monitoring: Data will be entered after every day of work and supervised by guide.
4. Statistical Analysis:

   1. Chi square test to compare the categorical data between the groups.
   2. Paired t test for comparing normally distributed continuous variables at different time point within the group
   3. Independent 't' test for comparing normally distributed continuous variables at different time point between the groups
   4. Wilcoxon signed rank test to compare the not normally distributed variables, ordinal data
   5. Mann- Whitney U test to compare the not normally distributed variables, ordinal data.
   6. Kaplan-Meier curves to compare the response rate on each follow up visit between the groups.

Test of significance will be considered when value of p ≤ 0.05.

Group A - will receive IL MMR Group B- will receive IL Vitamin D3

Only patients will be blinded to the randomization and intervention.

A Comparative Study to Assess Efficacy of Intralesional MMR Vaccine and Intralesional Vitamin D3 in Treatment of Warts

A Comparative Study to Assess Efficacy of Intralesional MMR (Measles, Mumps, Rubella) Vaccine and Intralesional Vitamin D3 in Treatment of Warts

Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions

Frequency of different types of past treatment taken- either traditional or medical treatments

Percentage of patients showing complete response to IL MMR and IL Vitamin D3

Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)

Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate

Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed

Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.

The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.

Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life

.

Nepal Health Research Council

B.P. Koirala Institute of Health Sciences

Junior Resident

All Group A patients will receive intralesional MMR.

Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.

Measles, Mumps, Rubella Vaccine

All Group B patients will receive intralesional Vitamin D3

Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6	NCT03058289	Breast Cancer Head and Neck C... Squamous Cell C... Lymphoma Pancreatic Canc... Liver Cancer Colon Cancer Lung Cancer Bile Duct Cance... Chordoma of Sac... Sarcoma	INT230-6 anti-PD-1 antib... anti-CTLA-4 ant...	18 Years -	Intensity Therapeutics, Inc.
A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin	NCT04059588	Cancer Solid Tumor Cancer of Skin	2141 V-11	18 Years -	Rockefeller University
A Comparative Study to Assess Efficacy of Intralesional MMR Vaccine and Intralesional Vitamin D3 in Treatment of Warts	NCT04428359	Verruca Viral	Measles-Mumps-R... Vit D	12 Years -	B.P. Koirala Institute of Health Sciences
A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6	NCT03058289	Breast Cancer Head and Neck C... Squamous Cell C... Lymphoma Pancreatic Canc... Liver Cancer Colon Cancer Lung Cancer Bile Duct Cance... Chordoma of Sac... Sarcoma	INT230-6 anti-PD-1 antib... anti-CTLA-4 ant...	18 Years -	Intensity Therapeutics, Inc.

Spots Global Cancer Trial Database for intralesional