A Study to Evaluate the Safety and Efficacy of SB206 in Subjects With Molluscum Contagiosum

This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled ascending dose study to be conducted in up to approximately 192 or 256 non-immunocompromised subjects with molluscum contagiosum. Subjects who satisfy entry criteria will be randomized 3:1 to ascending, sequential dose cohorts of SB206. The highest tolerated dose will also be run in a cohort once daily. Approximately 64 subjects will be randomized to each cohort. Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks. After 30 subjects randomized in a cohort have completed 2 weeks of treatment, the Data Safety Monitoring Board (DSMB) will review the available unblinded safety and tolerability data. The DSMB will determine if the data supports escalating to the next highest dose for the next cohort or if the data shows the dose is not tolerable decreasing to the next lower dose or frequency for the next cohort.

• SB206 4% (Drug), also known as NVN1000: Twice daily
• SB206 8% (Drug), also known as NVN1000: Twice daily
• SB206 12% (Drug), also known as NVN1000: Once or twice daily
• Placebo (Drug), also known as Vehicle Gel: Once or twice daily

Primary outcomes

• Proportion of Subjects Achieving Complete Clearance at Week 12 [12 weeks]: Percent (proportion) of subjects with complete clearance of all treatable MC at Week 12. This was measured by dividing the number of subjects who showed complete clearance by the number in that treatment group (this represents our primary outcome variable).

Secondary outcomes

• Proportion of Subjects Achieving Complete Clearance at Each Visit [Week 1; Week 2; Week 4; Week 8; Week 12]: Proportion of subjects achieving complete clearance of all treated molluscum contagiosum lesions at each visit.
• Time to First Complete Clearance [Week 12]: Median time to reach first complete clearance of all molluscum contagiosum lesions (Kaplan-Meier estimate)
• Proportion of Subjects Achieving 75% Reduction at Each Visit [Week 1, Week 2, Week 4, Week 8, Week 12]: Proportion of subjects achieving 75% reduction from baseline in number of molluscum contagiosum at each visit
• Mean Change in Molluscum Contagiosum at Each Visit [Week 1, Week 2, Week 4, Week 8, Week 12]: Mean change from baseline in number of molluscum contagiosum lesions at each visit
• Percent Change in Molluscum Contagiosum at Each Visit [Week 1, Week 2, Week 4, Week 8, Week 12]: Percent change from baseline in number of molluscum contagiosum lesions at each visit

Sex: All, ages: 2 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Be 2 years of age or older, and in good general health;
* Have signed written informed consent form by a parent or legal guardian (assent form where required);
* Have between 3 and 70 MC at baseline, excluding periocular (within 2 cm circumference of the eye) and lesions on the labia and penis;
* Females 10 years of age and older must have a negative urine pregnancy test prior to randomization;
* Females 10 years of age and older must agree to use an effective method of birth control during the course of the study and for 30 days after their final study visit;
* Be willing and able to follow study instructions and likely to complete all study requirements.

Exclusion Criteria:

* Are immunosuppressed, have immunodeficiency disorder, or are on immunosuppressive treatment;
* Have agminated MC that could make it difficult to provide accurate lesion counts;
* Have active atopic dermatitis with intense erythema and/or excoriations, that impact currently or could impact at any point during the study the ability to count MC lesions;
* Have significant eczematous reactions or other skin disease surrounding MC that may impact the ability to count lesions;
* Have received treatment with topical calcineurin inhibitors or steroids on MC or within 2 cm of MC lesions within 14 days prior to baseline;
* Have received treatment for MC during the 14 days prior to baseline with podophyllotoxin, imiquimod, cantharidin, sinecatechins, topical retinoids, oral or topical zinc, or other homeopathic or OTC products including, but not limited to, Zymaderm and tea tree oil, cimetidine and other histamine H2 receptor antagonists;
* Have received surgical procedures (cryotherapy, curettage, other) within 28 days prior to baseline;
* Have MC only in periocular area;
* Have MC only on the labia or penis;
* Female subjects who are pregnant, planning a pregnancy or breastfeeding;
* Have confirmed methemoglobin level of >3.0% at Baseline using a pulse co-oximeter;
* Have know hypersensitivity to any ingredients of SB206 or Vehicle Gel including excipients;
* Have participated in a previous study with NVN1000;
* Have participated in any other trial of an interventional investigational drug or device within 30 days or concurrent participation in another interventional research study.

Participant flow

Outcome results

• Proportion of Subjects Achieving Complete Clearance at Week 12 (Primary), Count of participants, Participants: Cohort 1: SB206 4% BID 5; Cohort 2: SB206 8% BID 16; Cohort 3: SB206 12% BID 13; Cohort 4: SB206 12% QD 18; Placebo (Vehicle Gel) 12
• Proportion of Subjects Achieving Complete Clearance at Each Visit (Secondary), Number, participants: Cohort 1: SB206 4% BID 0; Cohort 2: SB206 8% BID 1; Cohort 3: SB206 12% BID 0; Cohort 4: SB206 12% QD 1; Placebo (Vehicle Gel) 0
• Time to First Complete Clearance (Secondary), Median, Days: Cohort 1: SB206 4% BID NA (13 to 85); Cohort 2: SB206 8% BID 100.0 (11 to 100); Cohort 3: SB206 12% BID 91.0 (16 to 91); Cohort 4: SB206 12% QD 85.0 (8 to 86); Placebo (Vehicle Gel) 93.0 (17 to 93)
• Proportion of Subjects Achieving 75% Reduction at Each Visit (Secondary), Number, participants: Cohort 1: SB206 4% BID 1; Cohort 2: SB206 8% BID 1; Cohort 3: SB206 12% BID 3; Cohort 4: SB206 12% QD 3; Placebo (Vehicle Gel) 1
• Mean Change in Molluscum Contagiosum at Each Visit (Secondary), Least squares mean, Molluscum lesion counts: Cohort 1: SB206 4% BID -1.5 +/- 1.43; Cohort 2: SB206 8% BID 0 +/- 1.33; Cohort 3: SB206 12% BID -2.5 +/- 1.44; Cohort 4: SB206 12% QD -4.0 +/- 1.27; Placebo (Vehicle Gel) 0.7 +/- 1.13
• Percent Change in Molluscum Contagiosum at Each Visit (Secondary), Least squares mean, Percentage change from baseline: Cohort 1: SB206 4% BID 0.0 +/- 7.82; Cohort 2: SB206 8% BID 10.1 +/- 7.33; Cohort 3: SB206 12% BID -4.7 +/- 7.84; Cohort 4: SB206 12% QD -11.1 +/- 6.96; Placebo (Vehicle Gel) 8.7 +/- 6.16

Adverse events

Time frame: Baseline visit to end of study visit, 85 days.

Other adverse events by term

• Study Protocol (PDF, 2018-06-29)
• Statistical Analysis Plan (PDF, 2018-08-17)

• Tomoko Maeda-Chubachi, MD, Study chair, Novan, Inc.