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Randomized Controlled Trial
. 2024 Jan 1;160(1):63-70.
doi: 10.1001/jamadermatol.2023.4800.

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa: A Parallel-Design Double-Blind Trial

Hakim Ben Abdallah  1 , Anne Bregnhøj  1 , Thomas Emmanuel  1 , Gautam Ghatnekar  2 , Claus Johansen  1 , Lars Iversen  1
Affiliations
Randomized Controlled Trial

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa: A Parallel-Design Double-Blind Trial

Hakim Ben Abdallah et al. JAMA Dermatol. .

Abstract

Importance: Hidradenitis suppurativa is a painful immune-mediated disorder with limited treatment options; hence, a need exists for new treatments.

Objective: To evaluate the feasibility of heat shock protein 90 inhibition by RGRN-305 as a novel mechanism of action in treating moderate to severe hidradenitis suppurativa.

Design, setting, and participants: This was a parallel-design, double-blind, proof-of-concept, placebo-controlled randomized clinical trial conducted between September 22, 2021, and August 29, 2022, at the Department of Dermatology, Aarhus University Hospital in Denmark. The study included a 1- to 30-day screening period, a 16-week treatment period, and a 4-week follow-up period. Eligibility criteria included age 18 years or older and moderate to severe hidradenitis suppurativa with 6 or more inflammatory nodules or abscesses in at least 2 distinct anatomic regions. Of 19 patients screened, 15 patients were enrolled in the study. Intention-to-treat analysis was performed.

Interventions: Patients were randomly assigned (2:1) to receive oral RGRN-305, 250-mg tablet, or matching placebo once daily for 16 weeks.

Main outcomes and measures: The primary efficacy end point was the percentage of patients achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR-50) at week 16. Secondary efficacy end points included HiSCR-75 or HiSCR-90, Hidradenitis Suppurativa Physician's Global Assessment, Dermatology Life Quality Index scores, and a pain numeric rating scale. Safety was assessed by adverse events, physical examinations, clinical laboratory measurements, and electrocardiograms.

Results: A total of 15 patients were enrolled, completed the study, and were included in all analyses (10 [67%] female; median age, 29 [IQR, 23-41] years). The primary end point HiSCR-50 at week 16 was achieved by a higher percentage in the RGRN-305 group (60% [6 of 10]) than in the placebo group (20% [1 of 5]). Improvements were also observed across all secondary end points at week 16, including higher rates of the harder-to-reach HiSCR levels; 50% (5 of 10) achieved HiSCR-75 and 30% (3 of 10) achieved HiSCR-90, whereas none of the placebo-treated patients achieved HiSCR-75 or HiSCR-90. RGRN-305 was well tolerated, with no deaths or serious adverse events, and treatment-emergent adverse events were similarly frequent between the RGRN-305 and placebo groups.

Conclusions and relevance: The findings of this trial suggest that heat shock protein 90 inhibition by RGRN-305 offers a novel mechanism of action in treating hidradenitis suppurativa, warranting further evaluation in larger trials.

Trial registration: ClinicalTrials.gov Identifier: NCT05286567.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Emmanuel reported receiving grants from LEO Pharma and Janssen outside the submitted work. Dr Ghatnekar is an employee of Regranion LLC, and Regranion LLC has supported research at Aarhus University outside the submitted work. Dr Iversen reported being an employee of MC2 Therapeutics during the conduct of the study and receiving personal fees from AbbVie, Janssen, UCB, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flowchart
Figure 2.
Figure 2.. Time Course Response for Clinical Primary and Secondary End Points
A-C, Percentages of RGRN-305- and placebo-treated patients achieving Hidradenitis Suppurativa Clinical Response with a reduction of abscess and inflammatory nodule (AN) count of 50% (HiSCR-50), 75% (HiSCR-75) or 90% (HiSCR-90). D, Change from baseline in AN count by treatment group.
Figure 3.
Figure 3.. Secondary End Points at Week 16
A and B, Hidradenitis Suppurativa Physician’s Global Assessment (HS-PGA). C and D, Dermatology Life Quality Index (DLQI). E and F, Pain numeric rating scale (NRS). Mean changes were relative to baseline.
See this image and copyright information in PMC

References

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