Proof-of-concept Study Evaluating Subcutaneous Amlitelimab in Adult Participants With Moderate to Severe Hidradenitis Suppurativa

Study Overview
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Brief Summary
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This is a parallel, Phase 2, 2-arm, double-blind, randomized, multicenter, multinational, placebo-controlled study to evaluate efficacy, safety, pharmacokinetics (PK), and biological effects of treatment of subcutaneous injection of amlitelimab compared with placebo in male and female participants aged 18 to 70 years with moderate to severe hidradenitis suppurativa (HS). The purpose of this study is to measure standardized clinician reported and participant-reported outcomes (ClinRO and PRO), safety, and drug concentration. An optional open-label extension (OLE) period will assess chronic safety and efficacy over an additional 80 weeks of amlitelimab treatment. Study details include: The study duration will be up to 116 weeks, including a 4-week Screening period, a 16-week double-blind treatment period (DBT), an optional 80-week OLE period and a 16-week post-treatment follow-up period. All participants who complete the 16-week DBT period will be offered entry into an optional OLE. Participants who do not wish to enter the optional OLE period or who stop treatment prior to Week 16 (Visit 6) or stop investigational medicinal product (IMP) administration prior to completing the OLE period will proceed into the 16-week post-treatment follow-up period. The number of planned in clinic visits will be up to six during the DBT period with an additional eight during the OLE period, plus one post-treatment follow-up end-of-study visit. Up to 12 optional in clinic visits are allowed for participants who do not wish to self-administer IMP between scheduled in clinic visits during the OLE period.

Detailed Description
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The study duration per participant will be up to 116 weeks.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Proof-of-concept Study Assessing the Efficacy and Safety of Amlitelimab in Adult Participants With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis

Intervention / Treatment
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* Drug: Amlitelimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 (or country's age of majority if >18) years to 70 years of age inclusive, at the time of signing the informed consent. Participants with a history of signs and symptoms consistent with HS for at least 1 year prior to baseline. Participants must have HS lesions present in at least 2 distinct anatomic areas (eg, left, and right axilla; or left axilla and left inguino-crural fold), 1 of which must be Hurley Stage II or Hurley Stage III. Participant must have had an inadequate response to a trial of an oral antibiotic for treatment of HS Exclusion Criteria: Participants with a diagnosis of inflammatory conditions other than HS (including but not limited to systemic lupus erythematosus, systemic sclerosis, myositis, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, multiple sclerosis, Behcet's disease, sarcoidosis, etc) Any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with assessment of HS The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlitelimab<br>Subcutaneous injection (SC) as per protocol. | Drug: Amlitelimab<br>* Injection solution SC injection<br>* Other names: SAR445229;|
| Placebo Comparator: Placebo<br>Subcutaneous injection as per protocol. | Drug: Placebo<br>* Injection solution SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The clinical response as measured by the percentage of participants achieving HiSCR50 at Week 16 | Hidradenitis suppurativa clinical response (HiSCR)50 is defined as ≥50% reduction from baseline in the total abscess and inflammatory nodule count (AN count), with no increase from baseline in abscess or draining tunnel count. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of achieving HiSCR50 | HiSCR50 is defined as ≥50% reduction from baseline in the total abscess and inflammatory nodule count (AN count), with no increase from baseline in abscess or draining tunnel count. | From baseline to Week 16 | 
| Absolute change from baseline in AN count at Week 16 | AN count is the total abscess and inflammatory nodule count. | Baseline to Week 16 | 
| Percentage change in AN count at Week 16 | AN count is the total abscess and inflammatory nodule count. | Baseline to Week 16 | 
| Percentage of participants achieving HiSCR75 at Week 16 | HiSCR75 is defined as ≥75% reduction from baseline in the total abscess and inflammatory nodule count (AN count), with no increase from baseline in abscess or draining tunnel count. | Week 16 | 
| Percentage of participants achieving HiSCR90 at Week 16 | HiSCR90 is defined as ≥90% reduction from baseline in the total abscess and inflammatory nodule count (AN count), with no increase from baseline in abscess or draining tunnel count. | Week 16 | 
| Percentage of participants who experience improvement by at least 1 International Hidradenitis Suppurativa Severity Score System (IHS4) stage at Week 16 | The IHS4 is a validated tool to assess HS severity. A total score of 3 or less signifies mild, 4 to 10 signifies moderate, and 11 or higher signifies severe disease. | Week 16 | 
| Change in absolute score from Baseline in IHS4 at Week 16 | The IHS4 is a validated tool to assess HS severity. A total score of 3 or less signifies mild, 4 to 10 signifies moderate, and 11 or higher signifies severe disease. | Baseline to Week 16 | 
| Percentage of participants who experience a flare at Week 16 | A flare is defined as at least a 25% increase in AN count (with a minimum increase of 2 AN) relative to baseline. AN count is the total abscess and inflammatory nodule count. | Week 16 | 
| Percentage of participants achieving IHS4-55 at Week 16 | IHS4-55 is defined as achievement of a 55% reduction in IHS4 score from baseline. A total score of 3 or less signifies mild, 4 to 10 signifies moderate, and 11 or higher signifies severe disease. | Week 16 | 
| Percentage of participants achieving at least 30% reduction and at least 1 unit reduction from Baseline in weekly average of daily HS-Skin Pain NRS at Week 16 among participants with baseline NRS ≥3 | Hidradenitis Suppurativa-Skin pain-numeric rating scale (HS-Skin pain NRS) is scored on a 0 to 10 scale with 0 indicating no skin pain and 10 indicating worst skin pain possible. | Week 16 | 
| Percentage of participants with improvement (reduction) in Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 from Baseline at Week 16 among participants with baseline PP-NRS ≥4 | PP-NRS is a validated single item 0 (no itch) to10 (worst itch imaginable) numeric rating scale assessing peak pruritus (itch). | Week 16 | 
| Percentage of participants who experience 5-point reduction in DLQI at Week 16 among participants with baseline DLQI ≥4 | Dermatology life quality index (DLQI) is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL). Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL. | Week 16 | 
| Change from Baseline in the total Hidradenitis Suppurativa Quality of Life (HiSQOL) score at Week 16 | HiSQOL is an instrument designed to measure the HS-specific health-related QoL of adults with HS. | Baseline to Week 16 | 
| Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interest (AESIs), and serious adverse events (SAEs) including local injection site reactions in the Safety Population |  | Baseline up to Week 116 | 
| Incidence of potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population |  | Baseline up to Week 116 | 
| Serum amlitelimab concentrations measured at prespecified time points in the PK population |  | Day 1 up to Week 116 | 
| Incidence of antidrug antibodies (ADA) of amlitelimab at prespecified timepoints in the ADA population |  | Day 1 up to Week 116 |