SAR444656 for Hidradenitis Suppurativa

(ZEN Trial)

Not currently recruiting at 81 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must not be taking: Antibiotics, Antivirals, Antifungals, Antihelminthics

Disqualifiers: Active skin disease, Chronic infection, Malignancy, Cardiovascular events, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: up to 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called SAR444656 (also known as KT-474 or KYM-001) for individuals with moderate to severe hidradenitis suppurativa, a chronic skin condition causing painful lumps under the skin. The study aims to evaluate the effectiveness and safety of this treatment compared to a placebo. Participants will be divided into three groups: one taking a lower dose of the treatment, another taking a higher dose, and a third taking a placebo. Eligible participants must have had hidradenitis suppurativa for at least a year, affecting at least two body areas, and must not have responded well to antibiotics. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have any active or chronic infections requiring systemic treatment within 30 days before starting the trial, and you must not have used prescription topical therapies for HS within 14 days before the trial begins.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SAR444656, also known as KT-474, has undergone safety testing in earlier studies. In a previous trial, researchers evaluated this treatment in a controlled setting to assess its safety for people. The main focus of that study was safety, and the treatment was generally well-tolerated.

Reports from that study indicated that while some side effects occurred, they were mostly mild. Commonly reported issues included headaches and mild stomach discomfort. No serious side effects were linked to the treatment, which is a positive indicator for safety.

SAR444656 is also being studied for multiple conditions, suggesting ongoing confidence in its safety. This current study is in Phase 2, indicating that earlier trials demonstrated enough safety and potential benefits to continue research. While more information will emerge from ongoing studies, existing data supports that SAR444656 is relatively safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HS?

Most treatments for Hidradenitis Suppurativa, like antibiotics or biologics, focus on reducing inflammation. But SAR444656 offers something new. Researchers are excited about SAR444656 because it targets a different pathway in the body, potentially addressing the underlying causes of the condition more effectively. This oral treatment could offer a more convenient and less invasive option compared to injectable biologics, making it a promising alternative for those struggling with this chronic skin condition.

What evidence suggests that this trial's treatments could be effective for Hidradenitis Suppurativa?

Research shows that SAR444656, also known as KT-474, reduces inflammation by breaking down a protein called IRAK4. This protein is linked to inflammation, and lowering its levels can decrease inflammatory cytokines, which cause symptoms in conditions like hidradenitis suppurativa (HS). Early results suggest that this method might effectively treat HS by controlling inflammation. Previous studies with patients who have HS and atopic dermatitis showed promising results in reducing inflammation. Participants in this trial will receive either SAR444656 at one of two different doses or a placebo to evaluate its effectiveness in treating HS. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-70 with moderate to severe Hidradenitis Suppurativa (HS), having lesions in at least two areas and one area being Hurley Stage II or III. They must have had HS for over a year, not responded well to antibiotics for HS, have an active lesion count of 5 or more, fewer than 20 draining tunnels, and elevated CRP levels indicating inflammation.

Inclusion Criteria

I have HS lesions in at least 2 different areas, with one area being moderate or severe.

I have tried an oral antibiotic for HS for 3 months without improvement.

I am willing and able to keep a diary for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive SAR444656 or placebo orally for efficacy, safety, PK, and biological effects evaluation

up to 16 weeks

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SAR444656

Trial Overview The trial is testing SAR444656 against a placebo in adults with HS. Participants will be randomly assigned to receive either the drug or placebo during a treatment period of up to 16 weeks, followed by follow-up visits totaling up to 24 weeks duration.

How Is the Trial Designed?

Group I: SAR444656 dose 2 Experimental Treatment 1 Intervention

Participants will receive SAR444656 dose 2 orally

Group II: SAR444656 dose 1 Experimental Treatment 1 Intervention

Participants will receive SAR444656 dose 1 orally

Group III: Placebo Placebo Group 1 Intervention

Participants will receive placebo orally

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Kymera Therapeutics, Inc.

Industry Sponsor

Trials

8

Recruited

850+

Published Research Related to This Trial

A novel lotion containing triethyl-citrate, ethyl-linoleate, and g-peptide-10 was tested on 30 patients with mild to moderate hidradenitis suppurativa (HS) for eight weeks, showing significant improvement in both the Sartorius score and lesion counts.

The lotion was found to be effective and well-tolerated, with no reported side effects, making it a promising alternative to traditional antibiotic treatments that can lead to resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of a lotion containing triethyl citrate, ethyl linoleate, and GT peptide-10 in the adjuvant treatment of hidradenitis suppurativa: Real-life data. Skroza, N., Mambrin, A., Tolino, E., et al.[2019]

Adalimumab administered weekly is effective for treating hidradenitis suppurativa (HS), showing a significant reduction in Dermatology Life Quality Index (DLQI) scores compared to placebo, with a difference of 2.8 points.

Infliximab also shows moderate-quality evidence of benefit for HS, but evidence for other treatments is less robust or lacking, making it difficult to draw further conclusions about their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for Hidradenitis Suppurativa: Updated Summary of an Original Cochrane Review. Ingram, JR.[2018]

In a retrospective study of 6 patients with severe hidradenitis suppurativa, infliximab monotherapy led to significant improvements in symptoms, including reduced exudation and fewer lesions over a 6-month follow-up period.

The treatment was generally well tolerated, with only one mild infusion reaction reported, indicating a favorable safety profile for infliximab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab for the treatment of hidradenitis suppurativa. Fernández-Vozmediano, JM., Armario-Hita, JC.[2015]

The Fourth Annual Symposium on Hidradenitis Suppurativa brought together global experts to discuss recent advancements in understanding and treating hidradenitis suppurativa (HS), covering topics like clinical trials, pain management, and surgical options.

A special preconference workshop focused on innovative laser treatments for HS, highlighting the importance of advanced techniques like laser hair reduction and sinus tract deroofing in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proceeding report of the Fourth Symposium on Hidradenitis Suppurativa Advances 2019. Narla, S., Price, KN., Sachdeva, M., et al.[2021]

IL-17 inhibitors, particularly secukinumab and brodalumab, show promising efficacy in treating hidradenitis suppurativa (HS), with response rates of 57.1% and 100% respectively among 128 patients studied.

These treatments can be effective for patients who do not respond to other therapies, highlighting the need for standardized outcome measures to improve future research and clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review. Kashetsky, N., Mufti, A., Alabdulrazzaq, S., et al.[2022]

A systematic review of 5310 articles led to the analysis of 171 studies, resulting in evidence-based recommendations for managing hidradenitis suppurativa (HS), emphasizing the use of topical clindamycin for mild cases and biologic therapy like adalimumab for more severe cases after conventional treatments fail.

The review established that local surgical excision is recommended for mild-to-moderate HS, while more extensive disease may require wide excision, highlighting the need for tailored treatment approaches based on disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group. Zouboulis, CC., Bechara, FG., Dickinson-Blok, JL., et al.[2020]

Hidradenitis suppurativa (HS) is a challenging condition to treat, but recent guidelines recommend a combination of medical and surgical therapies, reflecting a growing understanding of the disease's complexity.

A systematic review of 365 papers identified 79 relevant studies, highlighting promising treatments such as infliximab, adalimumab, and ustekinumab, indicating a significant need for continued development of effective therapies for HS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New treatment strategies for hidradenitis suppurativa. Andersen, R., Jemec, GB.[2018]

A systematic review of 34 publications involving 105 patients with hidradenitis suppurativa (HS) found that TNF-alpha inhibitors, particularly infliximab, led to positive treatment outcomes in 90% of cases, indicating their potential efficacy in managing this challenging skin condition.

While side effects were reported in 8 out of 105 patients, they were similar to those seen in other studies with TNF-alpha inhibitors, suggesting a manageable safety profile; however, the need for more standardized reporting and randomized controlled trials is emphasized to better understand long-term effects and optimal treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors. Haslund, P., Lee, RA., Jemec, GB.[2018]

Hidradenitis suppurativa (HS) is a challenging skin condition marked by painful nodules and pus-filled lesions, primarily affecting areas like the armpits and groin, and current treatments are often inadequate.

The inaugural Symposium on Hidradenitis Suppurativa Advances highlighted the need for better understanding and research into HS, summarizing key areas such as its epidemiology, treatment options, and the importance of identifying gaps in knowledge to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major gaps in understanding and treatment of hidradenitis suppurativa. Hoffman, LK., Ghias, MH., Garg, A., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06028230

NCT06028230 | A Phase 2 Study to Evaluate the Efficacy ... This is a parallel, Phase 2, 3-arm study to evaluate the efficacy, safety, PK, and biological effects of SAR444656 compared with placebo in adult participants.

2. investors.kymeratx.com investors.kymeratx.com/news-releases/news-release-details/kymera-announces-expansion-kt-474-sar444656-hs-and-ad-phase-2

Kymera Announces Expansion of KT-474 (SAR444656) ... KT-474 (SAR444656) is a first-in-class IRAK4 degrader in development for the treatment of immune-inflammatory diseases with significant patient ...

3. nature.com nature.com/articles/s41591-023-02635-7

IRAK4 degrader in hidradenitis suppurativa and atopic ... KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and ...

4. dermatologytimes.com dermatologytimes.com/view/q-a-study-highlights-kt-474-s-effectiveness-in-targeting-irak4-for-hidradenitis-suppurativa-and-other-inflammatory-diseases

Q&A: Study Highlights KT-474's Effectiveness in Targeting ... KT-474, an IRAK4 degrader, has been shown to reduce IRAK4 levels and inhibit inflammatory cytokines, suggesting it could be effective for HS, atopic dermatitis ...

5. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.4c01305

Discovery of KT-474 a Potent, Selective, and Orally ... This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37957373/

IRAK4 degrader in hidradenitis suppurativa and atopic ... KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and ...

7. kymeratx.com kymeratx.com/wp-content/uploads/2022/10/Kymera-TPD-Plenary_Jared_Gollob_-20221026_.pdf

Phase 1 Single and Multiple Ascending Dose Trial of KT- ... These statements include information about our current and future prospects and our operations and financial results, which are based on currently available.