Study to Evaluate the Efficacy, Safety, and Tolerability of Efzofitimod in Patients With Systemic Sclerosis (SSc)-Related Interstitial Lung Disease (ILD) (SSc-ILD)

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo-controlled, PoC study to evaluate the efficacy, safety, and tolerability of efzofitimod in patients with SSc-ILD. The primary objective of the study is to evaluate the PoC for efficacy in a population with SSc-ILD. While improvement of ILD is the outcome of interest, the study will also evaluate changes in the skin. After initial screening (up to 4 weeks), approximately 25 eligible participants will be randomized 2:2:1 to 1 of 2 active (experimental) dose arms or placebo, administered every 4 weeks up to and including Week 20.

Official Title
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Randomized, Double-blind, Placebo-controlled Proof-of-Concept (PoC) Study to Evaluate the Efficacy, Safety, and Tolerability of Efzofitimod in Patients With Systemic Sclerosis (SSc)-Related Interstitial Lung Disease (ILD) (SSc-ILD)

Conditions
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Interstitial Lung Disease

Intervention / Treatment
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* Drug: efzofitimod 450 mg
* Drug: efzofitimod 270 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of SSc based on ACR/ EULAR criteria (2013) Overall duration of SSc < 48 months from the first non-Raynaud symptom manifestation HRCT obtained at the Screening Visit or within the 3 months prior to Screening consistent with SSc-ILD (adjudicated by a central reader) AND with pulmonary involvement > 10% Clinical presentation at Screening consistent with lcSSc (up to 40% of patients) or dcSSc Presence of at least: Any 1 laboratory marker for active disease OR Clinically significant decline in FVC % predicted (%pred) based on ≥ 105% relative decline over the preceding one year (two readings from the same pulmonary function laboratory) MMF of ≥ 2 gm/day (or equivalent doses of other mycophenolate based compounds) for 6 months Exclusion Criteria: Pulmonary disease with FVC %pred ≤ 45% OR DLco %pred ≤ 30%; FEV1/FVC ratio < 0.7 Participants with pulmonary artery hypertension on parenteral therapy or with clinical evidence of right heart failure HRCT obtained in the 3 months prior to Screening consistent with other confounding pathology. Treatment with corticosteroids (> 10 mg/day of prednisone or equivalent) within 2 weeks prior to baseline SSc-ILD treatments other than MMF OR MMF < 2 gm/day Any previous treatment with any of the following: rituximab, intravenous immune globulin (IVIG), nintedanib, tocilizumab, cyclophosphamide, pirfenidone, tyrosine-kinase inhibitors (e.g., imatinib, nilotinib, dasatinib) Rheumatic autoimmune disease other than SSc, Is an active, heavy smoker of tobacco/nicotine-containing products History of (anti-Jo-1) anti-synthetase syndrome or Jo-1 positive at Screening

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efzofitimod 450 mg<br>Administered IV infusion | Drug: efzofitimod 450 mg<br>* IV infusion over approximately 60 minutes every 4 weeks<br>|
| Experimental: efzofitimod 270 mg<br>Administered IV infusion | Drug: efzofitimod 270 mg<br>* IV infusion over approximately 60 minutes every 4 weeks<br>|
| Placebo Comparator: Placebo<br>Administered IV infusion | Drug: Placebo<br>* IV infusion over approximately 60 minutes every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in forced vital capacity (FVC) in mL |  | 24 weeks | 
| Annual rate of decline in FVC in mL |  | 24 weeks | 
| Annual rate of decline in FVC in percent predicted |  | 24 weeks | 
| Proportion of patients with > 5% and ≥ 10% decline in absolute FVC |  | Baseline to week 24 | 
| Proportion of patients with > 5% and ≥ 10% decline in percent predicted FVC |  | Baseline to Week 24 | 
| Change in HRCT fibrosis score |  | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ILD, SSc-ILD, Interstitial Lung Disease, lung inflammation, fibrosis, pulmonary function, efzofitimod, systemic sclerosis