| CTRI Number |
CTRI/2023/07/054769 [Registered on: 05/07/2023] Trial Registered Prospectively |
| Last Modified On: |
05/12/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
A Trial to Compare BI drug with Placebo for Patients With Scleroderma |
Scientific Title of Study
Modification(s)
|
A Phase II, randomised, placebo-controlled, double-blind, parallel-group, efficacy and safety study of at least 48 weeks of oral BI 685509 treatment in adults with progressive systemic sclerosis |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 1366-0031 version 4.0 dated 16 Nov 2023 |
Protocol Number |
| 2022-500332-11-00 |
EudraCT |
| NCT05559580 |
ClinicalTrials.gov |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
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| Phone |
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| Fax |
|
| Email |
|
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Details of Contact Person
Scientific Query
|
| Name |
Dr Shraddha Bhure |
| Designation |
Medical Director |
| Affiliation |
Boehringer Ingelheim India Pvt. Ltd. |
| Address |
Unit No. 202 and part of Unit no. 201, 2nd Floor Godrej 2, Pirojsha Nagar, Eastern Express Highway, Vikhroli (E), Mumbai
Mumbai
MAHARASHTRA
400079
India |
| Phone |
91227145-6484 |
| Fax |
|
| Email |
shraddha.bhure@boehringer-ingelheim.com |
|
Details of Contact Person
Public Query
|
| Name |
Jinu Jose |
| Designation |
VP, RDS Sales and Clinical Operations, India |
| Affiliation |
IQVIA RDS India Pvt Ltd |
| Address |
IQVIA RDS (India) Private Limited Omega Embassy Tech Square, Marathahalli - Sarjapura, Outer Ring Road, Kadubeesanahalli, Bengaluru, Karnataka
Bangalore
KARNATAKA
560103
India |
| Phone |
9886203019 |
| Fax |
|
| Email |
jinu.jose@iqvia.com |
|
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Source of Monetary or Material Support
|
| Boehringer Ingelheim International GmbH Binger Strasse 173 55216 Ingelheim am Rhein Germany |
|
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Primary Sponsor
|
| Name |
Boehringer Ingelheim |
| Address |
Middle East & North Africa (Scientific Office) FZ Limited, The Index Tower, Floor 13, Dubai International Financial Center, Dubai, United Arab Emirates |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| IQVIA RDS INDIA PRIVATE LIMITED |
Omega Embassy Tech Square, Marathahalli - Sarjapura, Outer Ring Road, Kadubeesanahalli, Bengaluru, Karnataka – 560103 |
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Countries of Recruitment
|
Argentina
Australia
Austria
Belgium
Brazil
Canada
China
Czech Republic
Denmark
Finland
France
Germany
Greece
India
Ireland
Israel
Italy
Japan
Malaysia
Mexico
Netherlands
New Zealand
Norway
Philippines
Poland
Portugal
Republic of Korea
Romania
Singapore
Spain
Sweden
Switzerland
Taiwan
Thailand
Turkey
United Kingdom
United States of America
Chile |
Sites of Study
Modification(s)
|
| No of Sites = 10 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Uma Kumar |
All India Institute of Medical Sciences |
Department of Rheumatology, Room No 4076, 4th Floor, Teaching Block, AIIMS, New Delhi -110029.
New Delhi
DELHI |
9868217040
umaakumar@yahoo.co.in |
| Dr Naisar Dilip Nahar |
Chopda Medicare & Research Centre Pvt. Ltd; Magnum Heart Institute |
3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner
Nashik
MAHARASHTRA |
9970222227
dr.naisar@yahoo.com |
| Dr Ajit Bapurao Nalawade |
Grant Medical Foundation Ruby Hall Clinic |
Department of Rheumatology , Super speciality building, 2nd Floor, Room No. 3,Grant Medical Foundation Ruby Hall Clinic, 40, Sassoon Road - 411001
Pune
MAHARASHTRA |
982274648
dr.ajitnalawade@gmail.com |
| Dr Puneet Kumar |
KG Medical University |
Dept of Rheumatology, LAL Bahadur Shastri Bhawan, RALC Campus, Lucknow 226018
Lucknow
UTTAR PRADESH |
9044373329
puneet_sarwan@rediffmai.com |
| Dr Jyotsna Oak |
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute |
Rao Saheb Achutrao Patwardhan Marg, Four Bungalows, Andheri
Mumbai
MAHARASHTRA |
9324717618
jyotsna.oak@kokilabenhospitals.com |
| Dr Sarath Chandra Mouli Veerava lli |
Krishna Institute of Medical Science Limited |
Department of Rheumatology and Clinical Immunology, Block 2, 3rd Floor, Krishna Institute of Medical Sciences Limited,1-8-31/1, Minister Road, Secunderabad-500003
Hyderabad
TELANGANA |
9866000685
sarath10@gmail.com |
| Dr Parasar Ghosh |
PGME&R and SSKM Hospital |
244. AJC Bose Road, Kolkata – 700020
Kolkata
WEST BENGAL |
9433988317
drparasar@gmail.com |
| Dr Shefali K Sharma |
Postgraduate Institute of Medical Education and Research |
Dept of Internal Medicine, 4th Floor, Sector-12, Chandigarh, UT-160012-India
Chandigarh
CHANDIGARH |
9417372439
sharmashefali@hotmail.com |
| Dr Padmanabha Shenoy |
Sree Sudheendra Medical Mission Hospital |
Kacheripady, Chittoor Road, Ernakulam, Kochi – 682018, Kerala, India
Ernakulam
KERALA |
9446567000
drshenoy@drshenoycare.com |
| Dr Vineeta Shobha |
St. John’s Medical College Hospital |
Unit of Hope, Department of Clinical Immunology and Rheumatology, St. John’s Medical College Hospital, Sarjapur Road,
John Nagar -560034
Bangalore
KARNATAKA |
9845021146
vineeta_shobha@yahoo.co.in |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 10 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee All India Institute of Medical Sciences_Dr. Uma Kumar |
Approved |
| Institutional Ethics Committee King George’s Medical University |
Approved |
| Institutional Ethics committee PGIMER |
Approved |
| Institutional Ethics Committee Poona Medical Research Foundation_Dr Ajit Nalawade |
Approved |
| Institutional Ethics Committee Sree Sudheendra Medical Mission_Dr Shenoy |
Approved |
| Institutional Ethics Committee St. Johns Medical College Hospital_Dr. Vineeta Shobha |
Approved |
| Institutional Ethics Committee_Dr Jyotsna Oak |
Approved |
| IPGME&R Research Oversight Committee_Dr Parasar Ghosh |
Approved |
| KIMS Ethics Committee, Krishna Institute of Medical Sciences Limited_Dr. Sarath Chandra Mouli Veeravalli |
Approved |
| Magna-Care Ethics Committee_Dr Naisar Dilip Nahar |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: M349||Systemic sclerosis, unspecified, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
BI 685509 |
Dose: 1 mg, Three times a day, 2 mg three times a day, 3 mg three times a day
Route: oral
Duration: 48 weeks
|
| Comparator Agent |
Placebo |
Dose: three times a day
Route: Oral
Duration: 48 Weeks
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female patients aged ≥18 years at time of consent (or above legal age, e.g. UK ≥16 years).
2. Patients must fulfil the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for SSc.
3. Patients must be diagnosed with diffuse cutaneous SSc (widespread skin fibrosis with skin involvement proximal to elbows and/or knees) as defined by LeRoy et al.
4. SSc disease onset (defined by first non-RP symptom) must be within 5 years of Visit 1.
5. 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 of either chest or abdomen within 6 months of Visit 1
OR
Worsening of skin thickening (≥2 mRSS points) within 6 months of Visit 1 OR
≥1 tendon friction rub.
6.Elevated biomarkers on Visit 1 (screening) defined as at least
one of the following:
C-reactive protein (CRP) ≥6 mg/L (≥0.6 mg/dL), OR
Erythrocyte sedimentation rate ≥28 mm/h, OR
Krebs von den Lungen 6 (KL-6) ≥1000 U/mL
7. 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 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 interstitial lung disease (ILD) has been confirmed
8. Evidence of early fibrosis at Visit 1, defined as a
mRSS of ≥12 points, AND
FVC ≥50% of predicted normal
9. If patients receive concomitant treatments for dcSSc, these need to be on stable doses for a predefined period.
10. Male patients able to father a child must be willing to use condoms if their sexual partner is a woman of childbearing potential (WOCBP). WOCBP must be ready and able to use highly effective methods of birth control per ICH M3 (R2). Such methods should be used throughout the trial. A list of contraceptive methods meeting these criteria is provided in the CTP |
|
| ExclusionCriteria |
| Details |
1. Any known form of pulmonary hypertension.
2. Limited cutaneous SSc at screening. Other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren syndrome.
3. Diffusing capacity for carbon monoxide (DLCO) (haemoglobin corrected) <40% of predicted at screening.
4. Any history of scleroderma renal crisis.
5. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology [CKD-EPI] formula) or on dialysis at screening.
6. Cirrhosis of any Child-Pugh class (A, B or C).
7. Cholestasis at present, or alkaline phosphatase (ALP) > 4 x upper limit of normal (ULN), or ALP > 2 x ULN and gammaglutamyl transferase (GGT) > 3 x ULN at Screening.
8. Known, severe gastric antral telangiectasias (watermelon stomach).
9. Any history of bronchial artery embolization or massive hemoptysis. (Massive hemoptysis is defined as acute bleeding >240 mL in a 24-hour period or recurrent bleeding >100 mL/day over consecutive days).
10. Active hemoptysis or pulmonary hemorrhage, including events managed by bronchial artery embolization.
11. Systolic blood pressure <100 mm Hg or known history of moderate or severe symptomatic orthostatic dysregulation as judged by the Investigator before start of trial treatment.
12. Sitting heart rate (HR) <50 beats per minute (BPM) at them Screening Visit.
13. Known heart failure with left ventricular ejection fraction <40% prior to screening.
14. A marked baseline prolongation of QT/QTc interval |
|
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Method of Generating Random Sequence
|
Other |
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Method of Concealment
|
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Blinding/Masking
|
Participant and Investigator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
The primary objective is to demonstrate superiority of BI 685509 at a target dose of 3 mg TID 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.
|
48 weeks
|
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| Secondary objectives are to demonstrate superiority of BI 685509 over placebo for absolute change from baseline in mRSS, FVC (% predicted), patient and physician global assessment, HAQ-DI, RP activity and DU net burden at Week 48, the ACR-CRISS, revised CRISS and for time to treatment failure. Additional objectives are to evaluate safety, PK, and exploratory biomarkers. |
48 weeks
|
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Target Sample Size
|
Total Sample Size="200"
Sample Size from India="6"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
20/07/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
12/12/2022 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="11"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
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Brief Summary
|
This is a multi-centre,
multi-national, prospective, randomised, placebo-controlled, double-blind, parallel-group, Phase
II clinical trial to investigate the efficacy and safety of oral BI 685509 at a
target dose of 3 mg TID, in adult patients with early progressive dcSSc and
vasculopathy.
Patients will be enrolled in the
trial and screened for eligibility once they have signed the informed consent.
The screening period has a maximum of 5 weeks. Eligible patients will proceed
to the 48-week treatment period. BI 685509 versus placebo use will be
established in a 1:1 randomisation after the screening period.
The treatment period includes a
4-week up-titration of BI 685509 from 1 mg to 3 mg TID: BI 685509 1 mg will be
given TID for 2 weeks. If tolerated, BI 685509 2 mg TID will be given for 2
weeks and then escalated to 3 mg TID. If the patient develops symptomatic orthostatic
hypotension on 2 mg TID, they will have to stop trial medication and contact
the site for dose adjustment. The same procedure will be followed after
escalation from 2 mg to 3mg. Every dose adjustment will require a patient visit
at the site. It is anticipated that approximately 10% of patients may not be
able to fully titrate up to the 3 mg TID dose. The main efficacy
analysis will be assessed at Week 48. After completing the first 48 weeks of
treatment, patients may continue to receive their assigned trial treatment in
the extended treatment period, until the last patient has completed the
treatment period. Patients will then enter a 4-week follow-up period that does
not include trial treatment, for ongoing safety and efficacy data collection.
The patient’s trial participation is complete when they have completed the last
planned visit (i.e., EOS, 4 weeks after EOT). |