Clinical trial NCT06195072: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Interstitial Lung Disease Due to Systemic Disease
Scleroderma
Keywords: platform
scleroderma
interstitial lung disease
systemic sclerosis
SSc
SSc-ILD
Lead sponsor: Scleroderma Research Foundation, Inc.
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Boehringer Ingelheim
First posted: 2024-01-08
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants who have given informed consent for the Master Protocol and all available Regimen-specific Subprotocols for which they are eligible will be randomly assigned to a regimen. Within each regimen, participants will be assigned to active treatment or matching placebo in a ratio detailed in the randomization scheme.

Eligibility for the Regimen will be based on the inclusion and exclusion criteria in the Master Protocol and on the inclusion and exclusion criteria in the Regimen-specific Subprotocol.

Importantly, to preserve the integrity of randomization, participants will be consented to all possible Regimen-specific Subprotocols open at that time, for which they qualify. Eligible participants will then be randomized to only one Regimen-specific Subprotocol, followed by randomization to the active IP treatment or to the corresponding placebo within a Regimen-specific Subprotocol.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Male or female 18+ years of age at the time of signed informed consent;
2. 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
3. Onset of SSc (defined by first non-Raynaud's symptom) 7 years or less prior to the Screening Visit;
4. A Modified Rodnan skin score (mRSS) less than 40
5. Presence of ILD with evidence of any fibrosis on HRCT (within 3 months or less of randomization)
6. Presence of an FVC 45% or more predicted normal;
7. 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:

1. 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);
2. Presence of infected ulcers or active gangrene at the Screening Visit;
3. History of scleroderma renal crisis within 6 months prior to the Screening Visit;
4. Forced expiratory volume in 1 second/FVC \<0.65 (pre-bronchodilator) at the Screening Visit
5. History of stem cell transplantation, bone marrow transplantation, chimeric antigen receptor T-cell therapy, or solid organ transplantation;
6. History of treatment with rituximab within the 6 months prior to the Screening Visit;
7. 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
8. Treatment with tocilizumab, nintedanib, pirfenidone, abatacept, leflunomide, tacrolimus, tofacitinib, intravenous immunoglobulin (IVIG), or any biologic or cyclophosphamide within 3 months prior to Screening Visit
9. 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.
10. 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.
11. 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
12. Presence of a concomitant life-threatening disease with life expectancy \<12 months based on the Investigator's assessment;
13. Evidence of active tuberculosis (TB) or being at high risk for TB

Other protocol and/or subprotocol exclusion criteria apply.

Primary outcomes:
measure: The change in forced vital capacity (FVC, in mL).
timeFrame: from baseline to the end of the treatment period at Week 52
Secondary outcomes:
measure: The percent change in high-resolution computed tomography (HRCT) quantitative interstitial lung disease - whole lung (QILD-WL);
timeFrame: from baseline to the end of the treatment period at Week 52
measure: The change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea score.
timeFrame: from baseline to the end of the treatment period at Week 52
measure: The proportion of study participants with an improvement in the revised CRISS score, in study participants with diffuse cutaneous SSc and baseline mRRS ≥10.
timeFrame: baseline, Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Division of Pulmonary and Critical Care Medicine
state: Alabama
city: Los Angeles
country: United States
facility: Keck School of Medicine at USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA) Ronald Reagan Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine - Epilepsy
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center - Department of Rheumatology
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center (UCMC)
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas School of Medicine
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University (BU)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health &amp; Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Houston
country: United States
facility: University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah Health Sciences Center
state: Utah
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Scleroderma Research Foundation
name: Kelly Oliver
role: STUDY_CHAIR
References: