A Study to Test the Efficacy and Safety of SAR442970 in Adults With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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This is a Phase 2 study in adult participants with moderate to severe hidradenitis suppurativa (HS). The purpose of the study is to evaluate the efficacy and safety of SAR442970 compared to placebo.

Detailed Description
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The study duration will be up to 40 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study Assessing the Efficacy and Safety of an Anti-TNF-OX40L NANOBODY® Molecule, SAR442970, in Participants With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: SAR442970
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a history of signs and symptoms consistent with hidradenitis suppurativa (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 inguinocrural fold), one 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, exhibited recurrence after discontinuation of antibiotics, demonstrated intolerance to antibiotics, or has a contraindication to oral antibiotics for treatment of their HS as assessed by the Investigator through participant interview and review of medical history. Participants must be either biologic and small molecule immunosuppressive-naïve or TNF-experienced. Participant must have a total abscess and inflammatory nodule (AN) count of ≥3 at the Baseline visit. Participant must have a draining tunnel count of ≤20 at the Baseline visit. Participant must have a C-reactive protein (CRP) >3 mg/L at the screening visit. Participant who is a candidate for systemic treatment per Investigator's judgment. Exclusion Criteria: Any other active skin disease or condition (eg, bacterial, fungal or viral infection) that may interfere with assessment of HS History of recurrent or recent serious infection Known history of or suspected significant current immunosuppression History of solid organ transplant History of splenectomy History of moderate to severe congestive heart failure Receipt of a live vaccine 12 week prior to Baseline visit or receipt of a killed vaccine 2 weeks prior to Baseline visit History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease Participants with a history of malignancy or lymphoproliferative disease other than adequately treated or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin that was excised and completely cured Participants with a diagnosis of inflammatory conditions other than HS Presence of active suicidal ideation, or positive suicide behavior or participant has a lifetime history of suicide attempt, or participant has had suicidal ideation in the past 6 months as indicated by a positive response using the screening or Baseline version of the Columbia-Suicide Severity Rating Scale (C-SSRS) or as assessed by the Investigator through participant interview and review of medical history A history of an adverse event (AE) to anti-TNF therapy (examples include, but are not limited, to serum sickness or anaphylaxis) for an HS or non-HS indication that would contraindicate readministration of an anti-TNF class therapy Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study Female participants who are breastfeeding or considering becoming pregnant during the study History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator Laboratory exclusion criteria apply 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: SAR442970<br>Participants will receive SAR442970 once every two weeks (Q2W) in Period A (Day 1 to Week 16). Participants will receive SAR442970 Q2W in Period B (Up to Week 28). | Drug: SAR442970<br>* 1 mL extractable volume of 150 mg/mL SAR442970 filled in 2 mL glass vial<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo Q2W in Period A (Day 1 to Week 16). Participants will receive SAR442970 Q2W in Period B (Up to Week 28). | Drug: Placebo<br>* 1 mL extractable volume of placebo filled in 2 mL glass vial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of biologic and small molecule immunosuppressive-naïve participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) | HiSCR50 is defined as at least a 50% reduction from Baseline in the total abscess and inflammatory nodule [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 |  | Up to week 16 | 
| Percentage of participants achieving HiSCR75 at Week 16 | HiSCR75 is defined as at least a 75% reduction from Baseline in the total abscess and inflammatory nodule [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 at least a 90% reduction from Baseline in the total abscess and inflammatory nodule [AN] count, with no increase from Baseline in abscess or draining tunnel count | Week 16 | 
| Percentage of participants who experience improvement by at least one International Hidradenitis Suppurativa Severity Score System (IHS4) stage at week 16 | The determination of IHS4 requires counting the inflammatory nodules, abscesses and draining tunnels and multiplying each by a specific coefficient | Week 16 | 
| Change in absolute score from Baseline in IHS4 at week 16 |  | From Baseline to week 16 | 
| Percentage of participants who experience a flare | Flare is defined as at least 25% increase in the total abscess and inflammatory nodule [AN] count (with a minimum increase of 2) relative to Baseline at week 16. | Week 16 | 
| Percentage of participants achieving IHS4-55 | IHS4-55 is defined as achievement of a 55% reduction in IHS4 score from Baseline | Week 16 | 
| Number of participants with treatment-emergent adverse events (TEAE), adverse events of special interest (AESI) and serious adverse events (SAE) including local reactions |  | Up to week 36 | 
| Percentage of participants achieving at least 30% reduction and at least 1 unit reduction from Baseline in weekly average of daily Hidradenitis Suppurativa Skin Pain Numeric Rating Scale (HS-SkinPainNRS) at Week 16 among participants with Baseline NRS ≥3 | Hidradenitis Suppurativa Skin Pain Numeric Rating Scale (HS-Skin Pain NRS) is based on worst skin pain in a 24-hour recall period (daily assessment is averaged over 7-day period) | Week 16 | 
| Serum SAR442970 concentrations throughout the study |  | Up to 36 weeks | 
| Incidence of anti-SAR442970 antibody positive response throughout the study |  | Up to 36 weeks |