Platform Clinical Study for Conquering Scleroderma

Official title

Platform Clinical Study for Conquering Scleroderma: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2b Platform Clinical Study to Evaluate the Safety and Efficacy of Investigational Products in Participants With Interstitial Lung Disease Secondary to Systemic Sclerosis

Overview

The goal of this clinical trial is to test efficacy of different investigational products (IPs) compared with placebo on the change from baseline to the end of the treatment period at Week 52 in lung capacity in participants with Interstitial Lung Disease Secondary to Systemic Sclerosis.

Interventions

• Drug Amlitelimab
  IP will be administered subcutaneously by the Investigator or designee as follows: * Amlitelimab or * Matching placebo
• Drug BI 1015550 (Nerandomilast)
  Study participants will take the active investigational product BI 1015550 (Nerandomilast) or matching placebo provided as film-coated tablets, administered orally BID.
• Drug Placebo
  see Experimental Arm intervention description

Primary outcome measures

• The change in forced vital capacity (FVC, in mL). [Time frame: from baseline to the end of the treatment period at Week 52]

Secondary outcome measures (3)

• The percent change in high-resolution computed tomography (HRCT) quantitative interstitial lung disease - whole lung (QILD-WL); [Time frame: from baseline to the end of the treatment period at Week 52]
• The change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea score. [Time frame: from baseline to the end of the treatment period at Week 52]
• The proportion of study participants with an improvement in the revised CRISS score, in study participants with diffuse cutaneous SSc and baseline mRRS ≥10. [Time frame: baseline, Week 52]

Eligibility criteria

Inclusion criteria

• Male or female 18+ years of age at the time of signed informed consent;
• SSc classification as defined by the 2013 American College of Rheumatology/European League Against Rheumatism criteria. Participants with diffuse, limited or sine cutaneous skin involvement are eligible
• Onset of SSc (defined by first non-Raynaud's symptom) 7 years or less prior to the Screening Visit;
• A Modified Rodnan skin score (mRSS) less than 40
• Presence of ILD with evidence of any fibrosis on HRCT (within 3 months or less of randomization)
• Presence of an FVC 45% or more predicted normal;
• Presence of a diffusing capacity of the lung for carbon monoxide (DLCO) 30% or more predicted normal, corrected for hemoglobin;

Other protocol and/or subprotocol inclusion criteria apply.

Exclusion criteria

• Presence of clinically significant pulmonary abnormalities inconsistent with ILD on HRCT (e.g., scarring due to previous active tuberculosis \[TB\], sarcoidosis, lung mass, or other findings unrelated to SSc-ILD, as determined by a local radiologist/Investigator);
• Presence of infected ulcers or active gangrene at the Screening Visit;
• History of scleroderma renal crisis within 6 months prior to the Screening Visit;
• Forced expiratory volume in 1 second/FVC <0.65 (pre-bronchodilator) at the Screening Visit
• History of stem cell transplantation, bone marrow transplantation, chimeric antigen receptor T-cell therapy, or solid organ transplantation;
• History of treatment with rituximab within the 6 months prior to the Screening Visit;
• History treatment with cell-depleting therapies other than rituximab, including, but not limited to, CAMPATH®; anti-cluster of differentiation (CD)3, anti-CD4, anti-CD5, antiCD19, and anti-CD20 agents; and investigational agents
• Treatment with tocilizumab, nintedanib, pirfenidone, abatacept, leflunomide, tacrolimus, tofacitinib, intravenous immunoglobulin (IVIG), or any biologic or cyclophosphamide within 3 months prior to Screening Visit
• History of use of any investigational medication or device for any indication within 30 days or 5 half-lives (whichever is longer) prior to Screening Visit.
• Presence of any of the following laboratory findings at the Screening Visit:

• Estimated glomerular filtration rate <45 mL/min/1.73 m2, calculated using the Chronic Kidney Disease Epidemiology Collaboration equation;
• Alanine aminotransferase or aspartate aminotransferase level > (2 x ULN);
• Platelets <100 × 109/L (100,000/μL);
• White blood cell count <2500/μL;
• Neutrophil blood count <1500/μL;
• Prothrombin time and partial thromboplastin time >1.5 × ULN, or international normalized ratio >2; or
• Any other laboratory test result, that in the opinion of the Investigator, might place the study participant at risk for participation in the study.
• Presence of a clinically significant disorder that, in the opinion of the Investigator, could contraindicate the administration of study product, affect compliance, interfere with study evaluations, or confound the interpretation of study results
• Presence of a concomitant life-threatening disease with life expectancy <12 months based on the Investigator's assessment;
• Evidence of active tuberculosis (TB) or being at high risk for TB

Other protocol and/or subprotocol exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 34 centers

• University of Alabama - Division of Pulmonary and Critical Care Medicine — Birmingham
• Keck School of Medicine at USC Medical Center — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• University of California, Los Angeles (UCLA) Ronald Reagan Medical Center — Los Angeles
• Stanford University Medical Center — Palo Alto
• Yale University School of Medicine - Epilepsy — New Haven
• Georgetown University Medical Center - Department of Rheumatology — Washington D.C.
• Emory University School of Medicine — Atlanta
• … and 26 more centers

Publications

• Khanna D, Evnin LB, Assassi S, Benton WW, Gordon G, Maslova K, Steffgen J, Maher TM. Design of CONQUEST, a novel, randomized, placebo-controlled, Phase 2b platform clinical trial to investigate new treatments for patients with early active systemic sclerosis with interstitial lung disease. J Scleroderma Relat Disord. 2024 Nov 5;10(2):121-132. doi: 10.1177/23971983241278079. eCollection 2025 Jun. PMID 39544897

Identifiers

NCT: NCT06195072 · SRF201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗