Efficacy and Safety of Topical Nitric Oxide-Releasing Berdazimer Gel in Patients With Molluscum Contagiosum: A Phase 3 Randomized Clinical Trial

Abstract

Importance: Molluscum contagiosum (MC) is a highly contagious skin condition. Lesions may persist for months to years, and no US Food and Drug Administration-approved medications are currently available in the US.

Objective: To assess the efficacy and safety of berdazimer gel, 10.3%, a novel topical nitric oxide-releasing medication, in the treatment of MC.

Design, setting, and participants: This was a multicenter, vehicle-controlled, double-blind, phase 3 randomized clinical trial (B-SIMPLE4) conducted in 55 clinics (mostly dermatology and pediatric) in the US from September 1, 2020, to July 21, 2021. Eligible participants were 6 months or older and had from 3 to 70 raised MC lesions. Patients with sexually transmitted MC or with MC only in the periocular area were excluded.

Interventions: Patients were randomized to treatment with berdazimer gel, 10.3%, or vehicle gel, applied as a thin layer to all lesions once daily for 12 weeks.

Main outcomes and measures: The primary efficacy end point was complete clearance of all MC lesions at week 12. Safety and tolerability measures included adverse event frequency and severity, and assessment of local skin reactions and scarring. Data analyses were performed from August 31, 2021, to September 14, 2021.

Results: A total of 891 participants were randomized, 444 to berdazimer, 10.3% (mean [range] age, 6.6 [0.9-47.5] years; 228 [51.4%] male; 387 [87.2%] White individuals), and 447 to vehicle (mean [range] age, 6.5 [1.3-49.0] years; 234 [52.3%] female; 382 [85.5%] White individuals). In the intention-to-treat population, 88.5% (393 patients) in the berdazimer group and 88.8% (397 patients) in the vehicle group had a lesion count performed at week 12. At week 12, 32.4% (144 patients) in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% (88 patients) in the vehicle group (absolute difference, 12.7%; odds ratio, 2.0; 95% CI, 1.5-2.8; P < .001) with 14.4% (64 patients) of the berdazimer group discontinuing treatment because of MC clearance compared with 8.9% (40 patients) of the vehicle group. Adverse event rates were low. The most common adverse events were application-site pain and erythema, mostly mild in severity. Adverse events leading to discontinuation affected 4.1% (18 patients) of the berdazimer group and 0.7% (3 patients) of the vehicle group. The most common local skin reaction was mild to moderate erythema.

Conclusions and relevance: Use of berdazimer gel, 10.3%, for MC appears to demonstrate favorable efficacy and safety with low adverse event rates.

Trial registration: ClinicalTrials.gov Identifier: NCT04535531.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Browning reported grants from Novan during the conduct of this study. Dr Cartwright reported equity in Novan during the conduct of the study and personal fees from Cassiopea outside the submitted work. Dr A. Hebert reported grants from The University of Texas Health Science Center McGovern Medical School−Houston during the conduct of the study. Dr Paller reported personal fees from Novan Data and Safety Monitoring Board during the conduct of the study. Dr D. Herbert reported equity in Novan and Radius during the conduct of the study. Ms Kowalewski reported a grant from Novan for a collaborative biostatistics agreement with the University of North Carolina at Chapel Hill during the conduct of the study. Ms Enloe reported equity in Novan during the conduct of the study. Dr Maeda-Chubachi reported equity in Novan during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

aAfter 200 patients were randomized, a data safety monitoring board reviewed all available unblinded safety data, including completed patch testing results for allergic dermatitis, and recommended that the study proceed without modification.

Figure 2.. Molluscum Contagiosum Lesion Clearance Through Week 12

A, Percentage of patients in the ITT population who achieved complete clearance of molluscum contagiosum lesions (defined as having a lesion count of 0) through week 12. B, Percentage of patients in the ITT population with 0 or 1 lesion(s) at week 12. C, Percentage of patients in the ITT population with ≥90% clearance at week 12. P values are based on logistic regression analysis of the treatment differences (berdazimer gel to vehicle) adjusted for the following factors: investigator type (dermatologist vs other), number of patients per household (1 vs 2), baseline BOTE inflammation score (0 vs ≥1), age in years (6 months to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, 7 to <8, 8 to <9, 9 to <12, and ≥12), and baseline lesion count. BOTE denotes beginning-of-the-end and ITT, intention-to-treat.

Figure 3.. Molluscum Contagiosum Lesion Count, Mean Percent Change From Baseline to Week 12

Data points are LS mean percent change in lesion count from baseline for the ITT population. Error bars indicate the standard error; P values for LS mean differences from vehicle (berdazimer gel to vehicle) are from mixed-model repeated-measures analyses with treatment, visit, treatment-by-visit interaction, investigator type (dermatologist vs other), household number of randomized patients (1 vs 2), baseline BOTE score (0 vs ≥1), age, and baseline lesion count as factors with an unstructured covariance matrix. BOTE denotes beginning-of-the-end; ITT, intention-to-treat, and LS, least-squares.