ZEN: A Phase 2 Study to Evaluate the Efficacy and Safety of SAR444656 Compared With Placebo in Adult Participants With Moderate to Severe Hidradenitis Suppurativa
Study Details
Study Description
Brief Summary
This is a parallel, Phase 2, 2-arm study to evaluate the efficacy, safety, PK, and biological effects of SAR444656 compared with placebo in adult participants with moderate to severe HS aged ≥18 to 70 years.
Study details include:
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Screening period: up to 4 weeks (30 days)
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Treatment duration: up to 16 weeks
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Follow-up period: up to 4 weeks
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Total study duration: up to 24 weeks
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Number of visits: 14
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAR444656 Participants will receive SAR444656 orally |
Drug: SAR444656 (KT-474)
Oral Tablet
|
| Placebo Comparator: Placebo Participants will receive placebo orally |
Drug: Placebo
Oral Tablet
|
Outcome Measures
Primary Outcome Measures
- Percent change from baseline in total abscess and inflammatory nodule (AN) count [Week 16]
The AN count is the sum of the abscess count and inflammatory nodule count at any given clinical assessment. It is derived from the lesion counts count obtained as part of the HS clinical parameters.
Secondary Outcome Measures
- Proportion of participants achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR 50) [Week 16]
- Proportion of participants achieving AN count ≤2 [Week 16]
- Absolute change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) [Week 16]
- Proportion of participants with improvement from baseline in Hurley Stage [Week 16]
- Proportion of participants achieving AN50 (at least 50% reduction in the AN count relative to baseline) [Week 16]
- Change from baseline in participants reported daily worst pain using HS-Skin Pain-Numerical Rating Scale (HS-Skin Pain-NRS) [Week 16]
- Proportion of participants achieving improvement defined as at least 30% reduction and at least 1 unit reduction in participant daily worst pain using HS-Skin pain-NRS [Week 16]
- Change from baseline in the amount of analgesic [Up to Week 16]
- Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), investigational medicinal product (IMP) discontinuation due to TEAEs [Up to Week 20]
- Plasma SAR444656 concentration [Up to Week 16]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant with a history of signs and symptoms consistent with HS for at least 1 year prior to baseline.
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Participant must have HS lesions present in at least 2 distinct anatomic areas, one of which must be Hurley Stage II or Hurley Stage III.
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Participant must have had an inadequate response to at least a 3-month treatment of an oral antibiotic for treatment of HS as assessed by the Investigator.
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Participant must have a total AN count of ≥5 at the baseline visit.
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Participant must have a draining tunnel count of ≤20 at the baseline visit.
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Participant must have a CRP >3 mg/L obtained at screening.
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Participant must be willing and able to complete the diary for the duration of the study as required by the study protocol.
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Contraceptive use by men with a partner of childbearing potential and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion Criteria:
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Participant with any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with assessment of HS.
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Any active or chronic infection requiring systemic treatment (eg, antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to baseline.
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Known history of or suspected significant suppressed immune response, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
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Participant with history of solid organ transplant.
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Participant with history of splenectomy.
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Participant with history of any malignancy or lymphoproliferative disease, except if the participant has been free from disease for ≥5 years. Successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix are allowed.
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Participant with a diagnosis of chronic immune-mediated, inflammatory conditions other than HS
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Participant with family history of sudden death or long QT syndrome.
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Participant with history of congenital or drug-induced long QT syndrome.
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Participant with congestive heart failure (New York Heart Association Class 2 to 4), greater than Class 1 angina pectoris, acute coronary syndrome within prior 6 months, known structural heart disease.
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Participant with history of any major cardiovascular events (eg, myocardial infarction, unstable angina pectoris, coronary revascularization, stroke, or transient ischemic attack) at any time prior to screening.
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Participant with history of ventricular fibrillation, ventricular tachycardia, torsades de pointes, atrial fibrillation, syncope not explained by non-cardiac etiology.
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Participant with uncontrolled hypertension defined as consistent systolic blood pressure ≥150 mmHg or consistent diastolic blood pressure ≥90 mmHg despite antihypertensive medication.
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Participant received prescription topical therapies for the treatment of HS within 14 days prior to the baseline visit.
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Prior or active treatment with any systemic biologic (anti-TNF) therapy, anti-IL17 therapy, anti-IL1/anti-IL1 receptor therapy except for up to 20% of the total study population. Furthermore, this 20% of biologic-experienced participants must fulfilled one or more of the following conditions:
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Discontinued due to treatment related toxicity and/or
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Discontinuation is not related to lack or loss of therapeutic response.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Sanofi
- Kymera Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACT17841
- 2023-504328-25