A study in people with systemic sclerosis to test whether BI 685509 has an effect on lung function and other systemic sclerosis symptoms

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim RCV GmbH & Co. KG, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

25 Nov 2022 → 31 Jan 2026

Decision date (initial)

2022-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective is to assess superiority of BI 685509 over placebo based on the mean difference in annual rate of decline in FVC over 48 weeks. The treatment effect of primary interest will be based on all randomised patients including the effects of any changes of treatment, i.e., a treatment policy strategy will be used.

Secondary objectives 5

1. assess superiority of BI 685509 over placebo for absolute change from baseline in mRSS
2. DU net burden at Week 48, in the ACR-CRISS scores, proportions of responders based on the revised CRISS and for time to treatment failure at Week 48.
3. FVC (% predicted)
4. patient and physician global assessment
5. HAQ-DI and RP activity

Conditions and MedDRA coding

systemic sclerosis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
2. Male or female patients aged ≥18 years at time of consent (or above legal age, e.g. UK ≥16 years).
3. Patients must fulfil the 2013 ACR/EULAR classification criteria for SSc.
4. Patients must be diagnosed with limited or diffuse cutaneous SSc as defined by LeRoy et al. Patients diagnosed with limited cutaneous SSc may be included if they are anti Scl-70 antibody positive.
5. Diffuse cutaneous SSc disease onset (defined by first non-RP symptom) must be within 7 years of Visit 1. Limited cutaneous SSc onset must be within 2 years of Visit 1
6. Evidence of active disease, defined as having at least one of the following: - New onset of SSc within the last 2 years of Visit 1 OR - New skin involvement or worsening of two new body areas within 6 months of Visit 1 (out of the 17 body areas defined by mRSS assessment, documented in clinical files) OR - New involvement or worsening of one new body area if either chest or abdomen within 6 months of Visit 1 OR - Worsening of skin thickening (e.g. ≥2 mRSS points) within 6 months of Visit 1 OR - ≥1 tendon friction rub.
7. Elevated biomarkers on Visit 1 (screening) defined as at least one of the following: - CRP ≥6 mg/L (≥0.6 mg/dL), OR - Erythrocyte sedimentation rate (ESR) ≥28 mm/h, OR - KL-6 ≥1000 U/mL. --> If none of the three criteria are met or should not be available, the patient can be entered if the mDAI is ≥ 2.5.
8. Evidence of significant vasculopathy, defined as: - Active DU(s) on Visit 1 OR - Documented history of DU(s), OR - Previous treatment of RP with prostacyclin analogues or ≥ 1 other medications, including calcium channel blockers, nitrates, NO donors in any form, including topical; phosphodiesterase 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil); nonspecific PDE5 inhibitors (theophylline, dipyridamole) OR - RP with elevated CRP ≥6 mg/L --> If none of the four criteria above are met, the patient can be entered if the diagnosis of ILD has been confirmed
9. Further inclusion criteria apply.

Exclusion criteria 9

1. Any known form of pulmonary hypertension.
2. Pulmonary disease with FVC <50% of predicted at screening.
3. Other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren syndrome.
4. Diffusing capacity for carbon monoxide (DLCO) (haemoglobin corrected) <40% of predicted at screening.
5. Any history of scleroderma renal crisis within the last 6 months.
6. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (CKD-EPI formula) or on dialysis at screening.
7. Cirrhosis of any Child-Pugh class (A, B or C)
8. Cholestasis at present, or ALP > 4 x ULN, or ALP > 2 x ULN and GGT > 3 x ULN at screening.
9. Further criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of decline (mL) in forced vital capacity (FVC) over 48 weeks

Secondary endpoints 13

1. Key secondary endpoint: Absolute change from baseline in mRSS at Week 48 in study participants with dcSSc
2. Key secondary endpoint: Proportion of responders in study participants with dcSSc based on the revised CRISS at Week 48 (Achievement of ≥ 20% improvement from baseline to Week 48 in at least 3 of the 5 core set measures, except ≥ 5% in FVC percent predicted
3. Key secondary endpoint: Absolute change from baseline in HAQ-DI score at Week 48
4. ACR-CRISS score at Week 48 in study participants with dcSSc
5. Absolute change from baseline in FVC (mL) at Week 48
6. Absolute change from baseline in FVC (% predicted) at Week 48
7. Absolute change from baseline in the PGA VAS score at Week 48
8. Absolute change from baseline in the CGA VAS score at Week 48
9. Composite measure of RP activity at Week 48
10. Absolute change from baseline in DU net burden at Week 48
11. Time to treatment failure, defined as the time to one of the following events (whichever occurs first) occurring over the 48-week and extended treatment period: - death, - absolute decline in percent-predicted FVC ≥10% relative to baseline, - ≥25% increase in mRSS and an increase in mRSS of >5 points, - initiation or dose change of immunomodulating/immunosuppressive therapy for clinically significant deterioration of SSc
12. Time to mRSS progression (≥25% increase in mRSS and an increase in mRSS of >5 points) in study participants with dcSSc
13. Proportion of study participants with dcSSc with mRSS progression (25% increase in mRSS and an increase in mRSS of >5 points)

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 1

Boehringer Ingelheim RCV GmbH & Co. KG

Sponsor organisation

Boehringer Ingelheim RCV GmbH & Co. KG

Address

Dr.-Boehringer-Gasse 5-11, Meidling Meidling

City

Vienna

Postcode

1121

Country

Austria

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Calle De Prat De La Riba 50

City

Sant Cugat Del Valles

Postcode

08173

Country

Spain

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

17 EU/EEA countries · 71 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 336 files

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

Application history

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