Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Condylomata Acuminata

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Genital Diseases

Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Imiquimod

Immunomodulating Agents

Immunologic Factors

Adjuvants, Immunologic

Interferons

2.5% imiquimod cream applied daily to wart area for up to 8 weeks

3.75% imiquimod cream applied daily to wart areas for up to 8 weeks.

placebo cream applied daily to wart areas for up to 8 weeks

daily topical application for up to 8 weeks

3.75% imiquimod cream

placebo cream

Jason Wu, MD

The purpose of this study is to determine whether imiquimod creams are effective in treating external genital warts (EGW). The secondary objective of this study is to provide information on recurrence of EGW. Additionally the study will also look at any adverse events associated with the use of the creams.

External genital and perianal warts are caused by the infection of human papillomavirus or HPV. HPV infection is a sexually transmitted disease (STD). External genital warts look like small flesh-colored, pink, or red growths on or around the external skin of sex organs or perianal area. The warts may look similar to the small parts of a cauliflower or they may be very tiny and difficult to see. They often appear in clusters of three or four, and may grow and spread rapidly. They usually are not painful, although they may cause mild pain, bleeding, and itching.

Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center, Efficacy and Safety Study of Imiquimod Creams in the Treatment of External Genital Warts

Proportion of subjects with complete clearance of all warts (both presented at Baseline and newly emerged warts) at End of Study. Primary analysis performed on the Intent to Treat population with imputation (Last Observation Carried Forward)for missing data points.

Local skin reactions in the treatment and/or immediate surrounding area were clinically identified as: erythema, edema, weeping/exudate, flaking/scaling/dryness, and erosion/ulceration. LSRs were visually assessed by investigator at each visit.

Rest period was a temporary interruption of dosing dur to intolerable LSRs.

Numbers of subjects in each treatment group reporting one or more adverse events

Graceway Pharmaceuticals, LLC

Jason Wu, MD / Exective Director, Product Development

The study duration included 5 month enrollment period, up to 28 week of study period, so total duration from first patient enrolled to the last patient completed study was approximately 12 months

2.5% imiquimod cream applied once daily to wart areas for up to 8 weeks

2.5% Imiquimod Cream

3.75% imiquimod cream applied once daily to wart areas for up to 8 weeks

3.75% Imiquimod Cream

Placebo cream applied once daily to wart areas for up to 8 weeks

Placebo

Total

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Robert Babilon, Vice President, Product Development

Adverse Reactions

Local Skin Reactions

Number of Subjects with Rest Period in Treatment

Safety Variables Include Adverse Reactions (AEs), Local Skin Reactions (LSRs), and Number of Subjects Who Took Rest Periods During the Treatment Period.

Proportion of Subjects With Complete Clearance of All Warts (Both Presented at Baseline and Newly Emerged Warts) at End of Study

Patients with adverse events considered probably related or related to the administration of the product.

Treatment Related Adverse Events

Overall Study

Ammonium trichloro(dioxoethylene-O,O'-)tellurate

Protective Agents

Radiation-Protective Agents

Reverse Transcriptase Inhibitors

Enzyme Inhibitors

Antiviral Agents

Topical 15% AS101 gel, once a day (overnight)

Vehicle, Once a day topical application (Overnight)

Administration of Topical 15% AS101 once a day (overnight)

15% AS101 gel

Administration of Vehicle once a day (overnight)

Vehicle

BioMas Ltd

Shabtai Romano, MD

Moshe Bustan, MD

Alon Ben-Arie, MD

Dora Milman, MD

Inbar Ben-Shachar, MD

David Peleg, MD

Dan Grisaru, MD PhD

Dan Grisaru, MD PhD Prof

Jacob Niv, MD

Yifat Oxhorn, MD

The purpose of this double blind study is to determine whether topical 15% AS101 gel is effective and safe as compared to vehicle in the treatment of external genital warts in women.

Females with external genital warts who meet the eligibility criteria will be randomly allocated in a blinded manner in 1:1 ratio to one of the 2 following study arms: (1) AS101 15% gel or (2) Vehicle. The patients will apply the study drug at home once daily (overnight) until complete clearance of external genital warts or for up to 14 weeks (98 days).

During therapy all patients will return to the clinic every 2 weeks plus/minus 3 days of the treatment visit for clinical assessments of the treated area.

At week 6 of treatment the investigator will evaluate the treated area for all patients. If the investigator determines that there is no change in the disease spread area or lesion number compared to Day 1, study therapy is to be discontinued prior to 14 weeks (98 days) of treatment and the patient will be considered as not cleared. Last observation carried forward (LOCF) method will be used to analyze such patients.

Patients who at week 6 were evaluated by the investigator to have a change in the disease spread area or lesion number compared to Day 1, will continue treatment until complete clearance of warts or up to a maximum of 14 weeks (98 days).

Patients who were evaluated during any of the treatment visits with complete clearance will stop to apply the study therapy, continue to be followed once per 4 weeks for 84 days (12 weeks) for safety and recurrence evaluation. Patients who completed treatment with partial clearance or patients who discontinued for reasons of other than complete clearance will be followed 28 days after discontinuation for disease progression and reference to other therapy if was recommended.

Should significant irritation or any other skin adverse reaction occur during the treatment period, study therapy may be held for up to 7 consecutive days on up to two separate occasions.

Unblinding: Patients will be revealed as to the nature of their treatment only after all patients have completed study.

In case of pregnancy or related serious adverse event the nature of the treatment will be revealed to the patient prior to end of study.

If the investigator determines that there is a disease progression in total lesion number or infected wart area size of the Day 1 treated area, study therapy is to be discontinued prior to 98 days of treatment.

Safety and Efficacy Double Blind Vehicle Controlled Study of 15% AS101 Gel to Treat External Genital Warts

A Phase II, Multicenter, Randomized, Double Blind, Vehicle Controlled Study Evaluating the Efficacy and Tolerability of AS101 15% Gel for External Genital Warts.

BioMAS Ltd

Neoplasms

Papilloma

LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks

LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks

Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks

Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks

Aldara 5% cream 3 applications per week for a maximum of 16 weeks

Investigational Treatment

Aldara

Novartis Pharmaceuticals

The LFX453X2202 study tested the investigational drug LFX453 against placebo for safety, tolerability, and efficacy in treating genital warts in circumcised men, in parallel with an additional open label arm using imiquimod 5%.

During the study the patients received either LFX453, placebo or active comparator and the tolerability and safety was assessed continuously through local tolerability assessments and adverse event recorded. Efficacy was clinical evaluations and lesion count. During the study biopsies were taken for analysis of pharmacokinetics and biomarkers. Blood samples were taken for safety, pharmacokinetics (PK), and biomarkers.

Efficacy and Tolerability of Topical LFX453 for External Genital Warts

A Randomized, Vehicle Controlled, Active Comparator, Parallel Group Study to Evaluate Efficacy, Safety, and Tolerability of Topical LFX453 Formulations in Patients With External Genital Warts (EGWs)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Number of participants achieving complete clearance of genital warts at Week 14

Number of participants with at least one AE/SAE in the category up to 30 weeks

Number of Participants that had partial clearance rate of at least 75 percent reduction in External Genital Wart (EGW)s count at end of treatment (EOT) Week 12 or 16

LFX453 0.1% NMC

LFX453 0.15% LCC

Vehicle to NMC

Vehicle to LCC

Age, Continuous

Study Director

Vehicle to nanomedicinal cream (NMC) and Vehicle to liquid crystal cream (LCC) Twice daily applications

Combined Vehicle

Pharmacodynamics (PD) data sets included all randomized patients For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.

Complete Clearance of Disease at Week 14

Adverse Events (AEs)

Serious Adverse Events (SAEs)

The safety analysis set included all patients that received any study drug. For Safety \& Tolerability only the 2 vehicles have separate analysis.

Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks

Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16

2.5% imiquimod cream applied daily to wart areas for up to 8 weeks

Placebo cream applied daily to wart areas for up to 8 weeks.

2.5% imiquimod cream applied daily to wart areas for up to 8 weeks.

2.5% imiquimod cream

3.75% imiquimod cream applied daily to wart areas for up to 8 weeks

Placebo cream applied daily to wart areas for up to 8 weeks

Placebo cream

Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts

A Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts

The complete clearance was defined as completely cleared all warts including baseline and newly emerged during the study at all anatomic areas.

Treatment related defined as "probably related" or "related" by investigator. Local skin reactions (LSRs)were part of the treatment related adverse events and assessed by the investigators.

Rest periods defined as temporary interruption of dosing due to intolerable local skin reaction.

Jason Wu, MD / Executive Director, Product Development

The study period included 4 month enrollment, maximum 28 weeks of study phase, so total length of the study from first patient enrolled to last patient completed the study is about 11 months.

2.5% imiquimod cream applied once daily to wart areas for up to 8 weeks.

3.75% imiquimod cream applied once daily to wart areas for up to 8 weeks.

Placebo cream applied once daily to wart areas for up to 8 weeks.

There was a high percentage of lost to follow up in this study. Since the disease studied in this study can be wait and watch, typically a high lost to follow up rate were seen in these kind of trials.

Proportion of Subjects Achieving Complete Clearance of All Warts (Baseline and New) at the End of Study.

Subjects with and Adverse Reactions (ARs)

Subjects with Any Local Skin Reactions (LSRs)

Number of Subjects who Took a Rest Period

Analysis population was based on safety population which defined as for all subjects randomized and received at lease one dose. There was one subject who randomized to the 2.5% group but received one treatment kit of 3.75% imiq cream, so this subject was assigned to 3.75% for the safety analysis.

Number of Subjects With Any Treatment Related Adverse Reactions (AEs), Any Local Skin Reactions (LSRs), and Number of Subjects Who Took Rest Periods During the Treatment Period

Cream containing 10% East Indian Sandalwood Oil (EISO)/Albuterpenoids

East Indian Sandalwood Oil Cream

Mark Lee, MD

This trial will be a phase 2, open-label, study to evaluate the safety, tolerability, and efficacy of VIR007 when administered topically for up to 60 days to adults between the ages of 18 to 65 years with a clinical diagnosis of external condylomata acuminata.

This trial will be a phase 2, open-label, study to evaluate the safety, tolerability, and efficacy of VIR007 when administered topically for up to 60 days to adults between the ages of 18 to 65 years with a clinical diagnosis of external condylomata acuminata.

Subjects will enter the Screening Period once the informed consent process has been completed. Subjects with a clinical diagnosis of external condylomata acuminata and who meet all inclusion and none of the exclusion criteria will be enrolled.

Once subject eligibility is confirmed and the screening procedures completed, the subject will start the Treatment Period of the study. All enrolled subjects will receive VIR007 (cream containing 10% EISO) with the first dose applied topically during Visit 1 (Day 1). Subjects will be instructed on how to apply the study medication twice daily for up to 60 days or until the Investigator determines the lesions have cleared. Subjects will return to the clinic for study-related assessments on Study Days 7, 14, 28, 42 and a Final Study Visit on Day 60. 30 days following complete resolution, as determined by the study investigator, or, on Study Day 90, subjects will receive a follow-up telephone call and be queried regarding condition status since study completion.

A Trial of a Botanical Drug Containing East Indian Sandalwood Oil (EISO) for the Treatment of External Genital Warts

A Phase 2, Open-label, Safety, Tolerability, and Efficacy Trial of a Botanical Drug at One Dose Level for the Treatment of External Condylomata Acuminata (Genital Warts) in Adult Immunocompetent Subjects

Safety will be assessed by evaluating adverse events (AEs) with respect to severity, duration, and relationship to study drug.

Tolerability will be assessed by the number of subjects reporting discomfort either during or immediately following the application of VIR007

The percentage of subjects achieving complete clearance of all EGW lesions over the course of the trial

Percentage of subjects continuing in remission at the follow-up call

Progressive Clinical Research

ViroXis Corporation

Cryotherapy and then Sinecatechins 15% Ointment 1 week later.

Cryotherapy will be standardized in all subjects and for all treated lesions: EGW lesions will be treated with 2 sprays, 5 seconds each, with a 5 second interval. All subjects will be treated with the same cryo-spray regimen.

Following cryotherapy, half of the subjects will be randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy (Week 1).

Sinecatechins 15% Ointment

Cryotherapy will be standardized in all subjects and for all treated lesions.

Cryotherapy alone

Gary Goldenberg, MD

External Genital Warts (EGW) are the most common sexually transmitted disease associated with more than 30 types of the Human Papillomavirus (HPV). Cryotherapy is an effective method of EGW treatment. However, multiple sessions may be required with reported clearance rates ranging between 27-88%. Sinecatechins 15% ointment is Food and Drug Administration approved for three times daily application in immunocompetent subjects 18 years and older for the treatment of EGW and perianal warts. Treatment of EGW with cryotherapy followed by sinecatechins appears to be logical. Cryotherapy has direct cytodestructive effects with immediate short-term efficacy on treated EGW, while sinecatechins provide field therapy, treating both clinical and sub-clinical lesions. For this study, the investigators used sinecatechins 15% ointment twice daily regimen and anticipated that the synergistic effect with cryotherapy will provide better efficacy that cryotherapy alone. The investigators also anticipated that the sequential therapy with be safe.

A total of 42 subjects received standardized cryotherapy to all lesions, using two cycles of five seconds each, separated by a five second interval rest (Week 0/Baseline). One week following cryotherapy, subjects were randomized 1:1 to either additional treatment with sinecatechins 15% ointment twice daily or no additional treatment. Those subjects randomized to additional treatment received sinecatechins 15% ointment BID for up to sixteen weeks, or until complete clearance of all EGW, whichever occurred first. Additionally, subjects were advised to maintain safe sexual practices and have all recent sexual partners examined for EGW. Subjects were followed every 8 weeks for a total of 16 weeks (Table 1). EGW lesion counts were conducted at all study visits by the same qualified blinded evaluator. Additionally, at each visit local skin reactions, change in concomitant medications, and adverse events were assessed. Any subjects who received sinecatechins 15% ointment and discontinued prematurely were asked to return for an End of Study Visit. Females of childbearing potential underwent a urine pregnant test at all visits during study treatment period. Subjects that met complete responder criteria as above, were additionally followed and assessed at Visit5/Week 41 and Visit 6/Week 65 to assess for wart recurrence.

Treatment of External Genital Warts With Cryotherapy and Sinecatechins 15% Ointment

An Investigator-Initiated Study to Assess the Safety and Efficacy of Sinecatechins 15% Ointment When Used in Conjunction With Cryotherapy in the Treatment of External Genital Warts

Subjects with complete clearance, or no longer have HPV infected cells. Complete clearance was defined as zero lesions at the respective time points.

To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 24 week post-treatment period.

To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 48 week post-treatment period.

To evaluate the safety of cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone as a regimen for EGW by evaluating for local skin reactions and adverse events.

Number of participants with local skin reactions.

Partial clearance is described as at least 50% reduction from baseline

Mean change in number of lesions after 1 weeks, 9 weeks and 17 weeks post treatment as compared to baseline

Mean change in number of lesions as compared to baseline at Week 1, Week 9 and Week 17 for the intent-to-treat population

Fougera Pharmaceuticals Inc.

Icahn School of Medicine at Mount Sinai

Assistant Professor

There were no serious adverse events related to the study medication reported during the study. All subjects experienced mild to moderate local site reactions (eg, any symptom of erythema, edema, scaling, crusting, and erosion which were not collected separately) that were related to both cryotherapy and/or sinecatechins ointment. There were no subject discontinuations or dose interruptions.

Cryotherapy and then Sinecatechins 15% Ointment 1 week later.

Sinecatechins 15% Ointment: Following cryotherapy, half of the subjects randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy up to 16 weeks or until complete clearance.

Sinecatechins 15% Ointment & Cryotherapy

Cryotherapy standardized in all subjects and for all treated lesions: EGW lesions treated with 2 cycles, 5 seconds each, with a 5 second interval. All subjects treated with the same cryo-spray regimen.

Cryotherapy Alone

Sinecatechins 15% Ointment: Following cryotherapy, half of the subjects randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy up to 16 weeks or until complete clearance.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00674739	Genital Warts	Imiquimod 3.75% imiquimod... placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Safety and Efficacy Double Blind Vehicle Controlled Study of 15% AS101 Gel to Treat External Genital Warts	NCT01943630	External Genita...	15% AS101 gel Vehicle	18 Years -	BioMAS Ltd
Efficacy and Tolerability of Topical LFX453 for External Genital Warts	NCT02482428	External Genita...	Investigational... Aldara	18 Years - 60 Years	Novartis
Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00674739	Genital Warts	Imiquimod 3.75% imiquimod... placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00735462	Genital Warts	2.5% imiquimod ... 3.75% imiquimod... Placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00735462	Genital Warts	2.5% imiquimod ... 3.75% imiquimod... Placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
A Trial of a Botanical Drug Containing East Indian Sandalwood Oil (EISO) for the Treatment of External Genital Warts	NCT03158974	Condylomata Acu...	East Indian San...	18 Years - 65 Years	ViroXis Corporation
Treatment of External Genital Warts With Cryotherapy and Sinecatechins 15% Ointment	NCT02147353	External Genita...	Sinecatechins 1... Cryotherapy alo...	18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for external genital warts