Infections

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Warts

Condylomata Acuminata

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

NVN1000 8% Gel

NVN1000 16%

Vehicle

NVN1000 24%

Joyce Rico, MD

A Phase 2 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Ascending Dose Study Assessing Tolerability, Safety, and Efficacy of Topical NVN1000 in Subjects with External Genital Warts and Perianal Warts

This is a phase 2, multi-center, randomized, double-blind, vehicle-controlled, ascending dose study to assess safety, tolerability and efficacy of a topical nitric oxide releasing compound in subjects with external genital and perianal warts. Eligible subjects will be treated with a topical gel (active or vehicle) for up to 12 weeks.

Topical NVN1000 for the Treatment of External Genital and Perianal Warts

A Phase 2, Multi-center, Double-blind, Randomized, Vehicle-controlled, Ascending Dose Study Assessing Tolerability, Safety, and Efficacy of Topical NVN1000 in Subjects With External Genital Warts and Perianal Warts

Clearance of baseline external genital and perianal warts at or before Week 12 as determined by physical examination by the investigator.

Comparison of scores for erythema, edema, erosions/ulcers, itch between active and vehicle treated subjects using a 4 point grading scale; on the tolerability scale, 0 = none and 3 = severe, indicating an increase in severity the higher the number assigned.

Safety population--Comparison of changes in methemoglobin levels between active and vehicle treated subjects. Methemoglobin levels were measured using a RAD-57 pulse co-oximeter. Values are expressed as a percentage of hemoglobin.

The percentage of subjects with complete clearance of baseline and warts that emerge during treatment period as determined by physical examination by the investigator

Percentage of subjects with complete or partial clearance of baseline warts as determined by physical examination by the investigator

Novan, Inc.

Safety population: The safety population included all randomized subjects with documented use of study medication (at least one application) at at least one post-baseline safety assessment.

NVN1000 8% Gel applied topically twice daily

Cohort 1: NVN1000 8% Gel Twice Daily

NVN1000 8% Gel applied topically once daily

Cohort 2: NVN1000 8% Gel Once Daily

NVN1000 16% Gel applied topically once daily

Cohort 3: NVN1000 16% Once Daily

Cohort 4: NVN1000 24% Once Daily

Vehicle Gel Once Daily

Vehicle Gel Twice Daily

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Current Tobacco Use

External genital warts (EGW) only

Perianal warts (PAW) only

EGW and PAW

Wart Location at Baseline

Baseline Wart Count

Intent to Treat Population (ITT)--the ITT includes all study subjects who were randomized and dispensed study medication.

Cathy White, Vice President, Drug Development Operations

ITT population. One subject in the NVN1000 8% Gel BID group was randomized but not dispensed treatment and thus was excluded from the ITT population..

Efficacy: Complete Clearance of Baseline External Genital and Perianal Warts at or Before Week 12

Erythema: Baseline

Erythema: Week 2

Erythema: Week 4

Erythema: Week 8

Erythema: Week 12

Edema: Baseline

Edema: Week 2

Edema: Week 4

Edema: Week 8

Edema: Week 12

Erosion/Ulceration: Baseline

Erosion/Ulceration: Week 2

Erosion/Ulceration: Week 4

Erosion/ulceration: Week 8

Erosion/ulceration: Week 12

Burning/stinging: Baseline

Burning/stinging: Week 2

Burning/stinging: Week 4

Burning/stinging: Week 8

Burning/stinging: Week 12

Tolerability of Topical NVN1000 Gel as Determined by Scores on a 4 Point Grading Scale for Erythema, Edema, Erosions/Ulcers, and Itch

Baseline

Week 2

Week 12

Safety as Determined by Changes in Laboratory Assessments

Percentage of Subjects With Complete Clearance of Total EGW/PAW at or Before Week 12

Percentage of Subjects With Complete or Partial Clearance of Baseline Warts at or Before Week 12

Overall Study

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

Age, Categorical

Age Continuous

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

Neoplasms

Papilloma

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

Immune System Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Cohort A - 200IU Leukocyte Interleukin, Injection 5 days/week x 2 weeks, off two weeks, then repeat 200IU 5 days/week x 2 weeks.

Arm B - 400IU Leukocyte Interleukin, Injection 5 days/week x 2 weeks, off 2 weeks, 400IU 5 days/week x 2 weeks.

Leukocyte Interleukin, Injection

Eyal Talor, PhD

Study is a dose escalation study. Fifteen patients will be enrolled in 2 treatment cohorts. Five participants (cohort A) will be treated with 200IU Multikine daily, 5 days/week for 2 weeks, off 2 weeks, then again 5 days/week for 2 weeks. If no serious adverse events are noted in cohort A patients, ten participants will be treated in cohort B. Cohort B participants will be treated the same as cohort A participants except that dose will be increased to 400IU Multikine per day.

Study is a dose escalation study to determine the safety of Leukocyte Interleukin, Injection in treating men and women with perianal warts who are HIV/HPV co-infected. Fifteen patients will be enrolled in 2 treatment cohorts. Five participants (cohort A) will be treated with 200IU Multikine daily, 5 days/week for 2 weeks, off 2 weeks, then treated again 5 days/week for 2 weeks. If no serious adverse events are noted in cohort A patients, ten (10) participants will be treated in cohort B. Cohort B participants will be treated in the same manner as cohort A participants except that the dose will be increased to 400IU Multikine per day.

Study of Leukocyte Interleukin, Injection for Treatment of Perianal Warts

Phase 1 Dose Escalation Study to Establish the Safety of Leukocyte Interleukin, Injection for Treatment of Perianal Warts in Adult Men and Women Who Are HIV/HPV Co-infected

Perianal wart characterization includes counting the number of identified warts, the diameter measurement of each identified wart in millimeters and the photographic imaging of each identified wart during the treatment phase and the follow-up phase of the study

HPV subtyping will be performed on specimens collected from the anal canal.

Anal dysplasia cytologic specimen collection will take place during the treatment phase and the follow-up phase of the study

Adverse effects experienced during the treatment phase of the study are recorded by the study participants in a symptoms log

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Topical NVN1000 for the Treatment of External Genital and Perianal Warts	NCT02462187	Genital Warts Perianal Warts	NVN1000 8% Gel NVN1000 16% Vehicle NVN1000 24%	18 Years - 50 Years	Novan, Inc.
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 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
Study of Leukocyte Interleukin, Injection for Treatment of Perianal Warts	NCT03038828	Perianal Warts	Leukocyte Inter...	18 Years -	CEL-SCI Corporation

Spots Global Cancer Trial Database for perianal warts