A study of different investigational treatments in people with the interstitial lung disease that accompanies scleroderma (CONQUEST)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Scleroderma Research Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

6 Aug 2024 → ongoing

Decision date (initial)

2024-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Scleroderma Research Foundation

External identifiers

EU CT number

2023-507129-40-00

WHO UTN

U1111-1295-0573

ClinicalTrials.gov

NCT06195072

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacodynamic, Efficacy, Pharmacokinetic, Safety

to evaluate the efficacy of the investigational products compared with placebo on the change from baseline to the end of the treatment period at Week 52 in forced vital capacity (FVC) (mL), measured in study participants with SSc-ILD

Secondary objectives 5

1. Efficacy of the investigational products compared with placebo as demonstrated by changes from baseline to Week 52 in the following: o Lung involvement as measured by high-resolution computed tomography (HRCT) quantitative ILD (QILD) - whole lung (WL)(QILD-WL); and o Dyspnea (severity and functional limitations), as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)- Dyspnea score.
2. Overall treatment response as measured by the Revised Composite Response Index in diffuse SSc (CRISS) score in study participants with diffuse cutaneous SSc and Baseline Modified Rodnan skin score (mRSS) ≥10 at Week 52.
3. Safety and tolerability of the investigational products.
4. SUBPROTOCOL A: 1-Efficacy of amlitelimab compared with placebo as demonstrated by changes from baseline to Week 52 in the following: - Skin thickness as measured by the modified Rodnan skin score (mRSS) in participants with diffuse cutaneous SSc and baseline mRSS ≥ 10; and - Overall health as measured by the Health Assessment Questionnaire – Disability Index (HAQ-DI), assessed with Scleroderma Health Assessment Questionnaire (SHAQ). 2-Pharmacokinetics (PK) of amlitelimab; and 3- Antidrug antibodies (ADA) to amlitelimab.
5. SUBPROTOCOL B: to evaluate the efficacy of BI 1015550 18 mg twice daily (BID) compared with placebo in study participants with diffuse cutaneous SSc and baseline mRSS ≥10 as demonstrated by the following: - Change from Baseline at Week 52 in mRSS; and/or - Achievement of disease improvement, as measured by the Revised Composite Response Index in SSc (CRISS) score at Week 52.

Conditions and MedDRA coding

interstitial lung disease secondary to systemic sclerosis (SSc-ILD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 prior to the Screening Visit;
4. A modified Rodnan skin score (mRSS) of less than 40;
5. Presence of ILD with evidence of any fibrosis on HRCT (within ≤3 months of randomization)
6. Presence of an FVC ≥45% predicted normal
7. Presence of a diffusing capacity of the lung for carbon monoxide ≥30% predicted normal, corrected for hemoglobin
8. Other protocol and subprotocol defined criteria apply.

Exclusion criteria 10

1. Scleroderma related: Presence of clinically significant pulmonary abnormalities inconsistent with ILD on HRCT (e.g., scarring due to previous active TB, sarcoidosis, lung mass, or other findings unrelated to SSc-ILD, as determined by a local radiologist/Investigator);
2. Prior treatment: History of stem cell transplantation, bone marrow transplantation, chimeric antigen receptor T-cell therapy, or solid organ transplantation;
3. Fertility: Women who are pregnant, nursing, or who plan to become pregnant while in the clinical study;
4. Liver: History of Child-Pugh Class B or Class C liver disease or presence of acute or chronic congestive heart failure ;
5. Laboratory abnormalities: Presence of abnormal laboratory findings at the Screening Visit:
6. Bleeding risk: History of major trauma or hemorrhage within 30 days of the Screening Visit;
7. Bleeding risk: History of any clinically significant chronic intermittent bleeding, such as active gastric antral vascular ectasia or active peptic ulcer disease, within 60 days of the Screening Visit;
8. Cardiovascular: History of any cerebrovascular events, myocardial infarction or unstable angina, restrictive or congestive cardiomyopathy (other than mild), life-threatening cardiac arrhythmias, hemodynamically significant aortic or mitral valve disease, pulmonary veno-occlusive disease. Presence of acute or chronic congestive heart failure, severe uncontrolled hypertension at the Screening Visit.
9. Scleroderma related: History of scleroderma renal crisis within 6 months prior to the Screening Visit.
10. Other protocol and subprotocol-defined criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in Forced Vital Capacity (FVC, in mL), assessed from Baseline to the end of the treatment period at Week 52.

Secondary endpoints 5

1. The change in HRCT QILD-WL from Baseline to the end of the treatment period at Week 52;
2. The change in FACIT-Dyspnea score from Baseline to the end of the treatment period at Week 52;
3. The proportion of study participants with an improvement in the revised CRISS score at Week 52, in study participants with diffuse cutaneous SSc and Baseline mRSS ≥10.
4. SUBPROTOCOL A: - The absolute change in mRSS from baseline to Week 52 in participants with diffuse cutaneous SSc and baseline mRSS ≥10; and - The absolute change in HAQ-DI, assessed with SHAQ, from baseline to Week 52
5. SUBPROTOCOL B: - Change from Baseline in mRSS at Week 52 in study participants with diffuse cutaneous SSc and baseline mRSS ≥10; - Achievement of disease improvement at Week 52, defined by Revised CRISS criteria in study participants with diffuse cutaneous SSc and baseline mRSS ≥10 (≥25% relative improvement [≥5% improvement for FVC percent predicted] from Baseline at Week 52 on at least 2 of the 5 core set measures, without worsening on more than 1 measure).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Scleroderma Research Foundation

Sponsor organisation

Scleroderma Research Foundation

Address

220 Montgomery Street Suite 484

City

San Francisco

Postcode

94104-3400

Country

United States

Scientific contact point

Organisation

Scleroderma Research Foundation

Contact name

Regulatory Submissions

Public contact point

Organisation

Scleroderma Research Foundation

Contact name

Regulatory Submissions

Third parties 15

Locations

11 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 166 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications