Infections

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Pharmaceutical Solutions

All Drugs and Chemicals

Immunomodulating Agents

Candida albicans Skin Test Antigen for Cellular Hypersensitivity will be administered as a 0.5 mL injection at the region of the interdigitated base of the treatment wart (epidermal/dermal junction) every 2 weeks for up to 10 injections

Matching placebo (sterile saline) will be administered as a 0.5 mL injection at the region of the interdigitated base of the treatment wart (epidermal/dermal junction) every 2 weeks for up to 10 injections

Injection at the base of the selected wart

Candin, Intradermal Solution

Placebo

Nielsen Central Contact

Jennifer Perry

Tim Dugan

Sandra Johnson, MD

Valerie Horne

Yelena Quintanilla

Sydney Fong

Theresa O'Lonergan

Ghadeer Samhan

Stella Schandorf

Lee Campbell

Kayleigh Koziol

Jeanette Caruso

Michelle Golding

Allison Kelly

Karina Garcia

Candice Nkwo

Celeste Katona

Kenji Mizoguchi

The goal of this clinical trial is to compare outcome in healthy subjects 12 years of age and older with at least 3, but no more than 20, common warts (Verruca vulgaris) following treatment with Candin or placebo. The main questions it aims to answer are:

* does treatment with Candin result in better clearance of warts than placebo
* how many injections are required to result in wart clearance Participants will
* have one wart selected for injection every two weeks until clearance
* return 12 weeks after wart clearance for assessment of durability of response

This study involves a comparison of an equal volume injection of Candin with an injection of placebo (unpreserved normal saline solution) in common warts. Subjects will be randomized 2:1 to receive Candin or placebo. During the Treatment Period, 1 dose (0.5 mL) of investigational product (IP) will be injected every 2 weeks into a single treatment wart until either clinical clearance of the treatment wart is achieved or a total of 10 injections have been administered.

Subjects achieving clinical clearance of the treatment wart will receive a final injection at the site of the cleared wart and then immediately enter the Observational Period for 12 weeks. Complete resolution is achieved when a subject demonstrates clinical clearance for 12 weeks.

Randomized, Double-Blind, Placebo-Controlled Study

Unblinded site staff will prepare syringes of study drug for administration by blinded study staff

Candin for the Treatment of Common Warts

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Candin for the Treatment of Common Warts (Verruca Vulgaris) in Adolescents and Adults

Absence of visual or measurable wart maintained through the entire Observational Period for injected wart

Time from first injection to achieving clinical clearance of the treatment wart. Clinical clearance is no evidence of the wart by visual inspection.

The injected wart and up to five other warts will be measured. Clinical clearance is no evidence of the wart by visual inspection.

Nielsen BioSciences, Inc.

Neoplasms

Rare Diseases

Melanoma

Neoplasm Metastasis

Pigmentation Disorders

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Aldesleukin

Interleukin-2

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Two subcutaneous intralesional injections of Aldesleukin, prepared by the pharmacy such that the contents will be masked, will be administered by the care provider in a clinic seven days apart.

Two subcutaneous intralesional injections of Saline, prepared by the pharmacy such that the contents will be masked, will be administered by the care provider in a clinic seven days apart.

0.1 mL of sterile saline solution (0.9% m/v)

Saline

Carman A Giacomantonio, MD, FRCSC

This study is meant to assess the use of intralesional IL-2 to modulate the immunological response to suspected melanoma, or melanoma in situ, in an effort to increase lymphocyte infiltration and decrease disease metastasis.

Patients that are clinically diagnosed with suspected Melanoma or Melanoma in situ will be assigned to either a treatment or control arm. The treatment group will be subjected to two intralesional IL-2 injections, whereas the control group will be subjected to two intralesional injections of saline.

The proteomic and metabolomic profiles of both groups will be analyzed using urine and blood samples in an effort to assess the systemic immunological response, if any, to the treatment. Also, upon disease confirmation and staging by a qualified pathologist, lesions will be assessed for lymphocyte infiltration using immunohistochemical methods.

This study will determine whether pre-treatment of IL-2 on lesions (clinically diagnosed as melanoma or melanoma in situ) is effective in generating an adaptive immune response, and whether that immune response may play a role in preventing disease metastasis.

This study is primarily designed to determine if tumor specific immunity can be generated in patients with highly suspicious pigmented lesions in response to intralesional IL-2, and whether that immunity can confer resistance to melanoma metastasis. Patients will be identified by qualified dermatologists and interviews will be held at the surgery clinic (4th floor Dickson Center) QEII HSC, NSHA.

The standard wait time from consultation to surgical biopsy is up to 4 weeks. Investigators will ensure that patients are seen immediately upon notification from participating dermatologist and all research components of the study are completed within the normally anticipated wait time. Through utilization of this standard wait time, intralesional IL-2 can potentially affect an immune response, that otherwise could not be achieved after the biopsy is completed. Given that the study is conducted within the normal wait time, it doesn't deviate from the normal standard of care. Following the study protocol, patients will receive intralesional injections on Day 1(Week 1 Visit) and Day 8 (Week 2 Visit), and excisional biopsies will be performed on Day 15 (Week 3 Visit), well within the accepted wait time from consultation to biopsy. The intralesional injections and collection of biospecimens beyond the biopsy deviate from but does not delay the normal standard of care. Two additional visits are required in addition to the initial consultation.

This study is a randomized, controlled, double-blind study. Patients with highly suspicious pigmented lesions will be randomly assigned by an algorithm to one of two groups: 1) treatment group patients will be treated intralesionally with IL-2 (Proleukin (Aldesleukin), Novartis Pharmaceuticals Canada Inc.) at a dose of 500,000 International Units (IU) in 0.1ml of sterilized saline (0.9%, m/v) for 2 treatment cycles 1 week apart (Day 1 and Day 7); 2) control group patients will be treated intralesionally with sterilized saline (0.9%, m/v) of the same volume (0.1ml). Randomization will be generated by a Random Block algorithm for each patient, and instruction preparation for each patient will be sent to pharmacy. IL-2 (Proleukin) will be obtained from Novartis by the pharmacy, paid for by Dr. Carman Giacomantonio's research services account. The pharmacy will be given instruction to prepare either IL-2 treatment or injectable control (saline). The pharmacy will assign a codified ID which will be provided along with the syringe with the patient name labeled as "Interleukin-2/Placebo" (thus blinding study to clinician and patient). As a pilot study, the principle of the design is to test the feasibility of proceeding to a larger and more expensive trial following the methodology and protocol proposed. As such there will be a minimum of 20 (10 treatment, 10 placebo) participants (up to a maximum of 60). It is estimated that statistical significance will be reached with 20 patients, however if it is not reached after 20 patients, an additional 10 (5 treatment, 5 control) patients will be enrolled. If significance is still not reached after 30 patients, an additional 10 patients will be enrolled and so on up to a maximum of 60 patients. If after 60 patients, significance is not achieved then further recruitment under the current protocol would not be logical and therefore the methodology would need to be revised or study discontinued.

On Day 1 (first treatment) and 15 (excisional biopsy), all patients will have blood (4 vials) and urine (25-50 ml) samples taken. Local reactions to injections will be monitored for non- specific signs such as bleeding, arythema, infection, or irritation. Investigators do not anticipate specific changes in the pigmented lesion related to the injection in this short time period, however all changes will be noted.

On Day 15, following the second intralesional injection an excisional biopsy will be performed following standard surgical techniques, as follows: ellipse of skin encompassing the pigmented lesion extending into the subcutaneous fat will be performed to achieve a grossly clear but narrow margin of excision. This small defect will be closed primarily with interrupted sutures. The biopsied specimen will be subsequently evaluated using standard histological techniques to confirm diagnoses, assess margin status (clear or involved) and depth of lesion invasion. The depth of lesion invasion will dictate the extent of subsequent surgical excisions and margin selection according to standard National Comprehensive Cancer Network (NCCN) guidelines. Pre-biopsy intralesional injections of 0.1ml into the lesion will not alter dimensions or architecture of the lesion or impact the extent the subsequent biopsy required. Lesions that are felt to be too large for closure without tissue manipulation or creation of flaps, will be biopsied using a punch biopsy sampling technique whereby 4mm diameter discs of tissue from representative areas of the lesion will be taken to confirm the diagnosis and the depth of invasion. The depth of invasion will dictate the extent and complexity of subsequent surgery required to remove the lesion and achieve clear margins according to NCCN guidelines. The biopsied specimen will be processed as follows: using a 22G needle a fine needle aspiration biopsy will be performed (the needle will be passed through the center of the lesion two times) for RNA analysis. The remainder of the tissue will be sent to pathology for standard histological assessment. The pathologist will also report the extent of observed tumor infiltrating lymphocytes (TILs) associated with treatment compared to control injections. Blood and urine will be assessed using metabalomic and proteomic methods to assess systemic immune response to treatment.

All blood, urine, and lesion biopsy samples will be labeled with a codified number (will not contain any patient identifying information) and will be immediately transported to Dr. Carman Giacomantonio laboratory at Dalhousie University for storage. Fine needle aspiration of excised samples will be assessed for tumor genetic and epigeneitic profile. Blood and urine will be assessed for proteomic and metabolomic profiles, respectively.

All study participants will receive assessments every 4 months for 2 years and biannual assessments for years 3 to 5 after the initial intervention to assess disease progression, or the development of new melanoma, to compare between both treatment and control groups. There is no standardize test or measurable biomarker to assess established or lasting immunity. This aspect of the study is identical to the patient assessment conducted as per standard of care for melanoma patients. Again, any publications of study results will be completed devoid of any information that could be used to identify patients included in the study.

Patients will be given either intralesional IL-2 or intralesional saline as a control

Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2

Data will be analyzed in order to achieve a statistically significant differentiation between treatment and control outcomes in study measures including tumor infiltrating lymphocytes (TILs) and circulating immunomodulators.

All patients will receive assessments every 4 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess disease metastasis in treatment and control groups. Both number of new metastases (integer value) and thickness (mm) will be measured as a part of this assessment.

RNA analysis of excised tissue will be compared to unaffected patient tissue obtained from the clear margins of the excisional biopsy to assess genetic changes resulting from the melanoma and treatment/placebo injections.

Proteomic analysis will be conducted on blood samples to assess systemic immune response to both treatment and control groups. Serum collected from patient blood samples will be used for proteomic analysis to assess protein expression, including circulating immunomodulators (cytokines and chemokines) before, and after, treatment. This study may serve to help develop diagnostic protocols and methods of assessing response to treatments.

Metabolomic analysis will be conducted on urine samples to assess systemic immune response to both treatment and control groups. All tumor and tissue produce by products in waste that are excreted by the kidneys. Urine samples can be evaluated using techniques, such as Mass Spectrometric, to determine if biological compounds can be identified in association with the presence of a malignant process that would not be produced by normal tissue.This study may serve to help develop diagnostic protocols and methods of assessing response to treatments.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Candin for the Treatment of Common Warts	NCT05889845	Common Warts (V...	Candin, Intrade... Placebo	12 Years -	Nielsen BioSciences, Inc.
Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2	NCT03233828	Melanoma (Skin) Melanoma in Sit...	Aldesleukin Saline	18 Years - 80 Years	Nova Scotia Health Authority
Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2	NCT03233828	Melanoma (Skin) Melanoma in Sit...	Aldesleukin Saline	18 Years - 80 Years	Nova Scotia Health Authority

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