Effectiveness and safety of riociguat in patients with sclerosis of the skin

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2014-001353-16-NL
• Date of registration: 20/10/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Effectiveness and safety of riociguat in patients with sclerosis of the skin
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
• Date of first enrolment: 31/12/2014
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001353-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Japan, Netherlands, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent
2. Men or women aged 18 years and older
3. Systemic sclerosis, as defined by ACR/EULAR 2013 criteria
4. dcSSc according to the LeRoy criteria, i.e., skin fibrosis proximal to the elbows and knees in addition to acral fibrosis.
5. Disease duration of = 18 months (defined as time from the first non-Raynaud’s phenomenon manifestation)
6. = 10 and = 22 mRSS units at the screening visit
7. FVC = 45% of predicted at screening
8. DLCO = 40% of predicted (hemoglobin-corrected) at screening
9. Negative serum pregnancy test in a woman of childbearing potential at the screening visit
10. Women of childbearing potential must agree to use adequate contraception when sexually active. “Adequate contraception” is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies since signing of the informed consent form until 30 (+5) days after the last study drug administration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
1. Limited cutaneous SSc at screening
2. Major surgery (including joint surgery) within 8 weeks prior to screening
3. Hepatic insufficiency classified as Child-Pugh C
- Patients with isolated AST or ALT >3xULN or bilirubin >2xULN can be
included in the trial under the condition of additional monitoring during
the trial
4. Estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m2 (Modification of Diet in Renal Disease formula) or on dialysis at the screening visit.Patients entering the trial with eGFR 15-29mL/min/1.73m2 will be undergo additional monitoring of renal function
- Because the MDRD formula is thought to cause significant bias for Japanese patients, the equation for Japanese patients is: 194 x serum creatinine (mg/dL) -1.094 x Age -0.287 x 0.739 (if female).
5. Any prior history of renal crisis
6. Sitting SBP < 95 mmHg at the screening visit
7. Sitting heart rate < 50 beats per minute (BPM) at the screening visit
8. Left ventricular ejection fraction < 40% prior to screening
9. Any form of pulmonary hypertension as determined by right heart catheterization
10. Pulmonary disease with FVC < 45% of predicted or DLCO (hemoglobin-corrected) < 40% of predicted at screening
11. Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
12. Not permitted prior and concomitant medication(updated)
13. pregnant or breast feeding women
14. Women of childbearing potential not willing to use adequate contraception and not willing to agree to 4-weekly pregnancy testing from Visit 1 (first administration of study drug) onwards until 30 (+5) days after last study drug intake.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

diffuse cutaneous systemic sclerosis (dcSSc)
MedDRA version: 19.0 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: Adempas
Product Name: riociguat coated tablet 0.5 mg
Product Code: BAY63-2521
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Adempas
Product Name: riociguat coated tablet 1.0 mg
Product Code: BAY63-2521
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Adempas
Product Name: riociguat coated tablet 1.5 mg
Product Code: BAY63-2521
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Adempas
Product Name: riocigu

Primary Outcome(s)

Main Objective: The primary objective of this study is to assess the efficacy of riociguat administered 3 times a day (TID) as compared with placebo in terms of change in the mRSS from baseline to Week 52.

Primary end point(s): Change in mRSS from baseline to Week 52

Secondary Objective: Key secondary objective:
o CRISS at Week 52, consisting of five variables: mRSS, FVC % predicted, physician and patient global assessments and HAQ-DI score (from SHAQ patient reported outcome)
Further secondary objective:
o HAQ-DI domain (separately from SHAQ as part of the calculation of the CRISS algorithm)
o SHAQ as part of the calculation of the CRISS algorithm
o Patient’s global assessment
o Physician’s global assessment
o Change in FVC (forced vital capacity) % predicted

Timepoint(s) of evaluation of this end point: week 52

Secondary Outcome(s)

Secondary end point(s): Key secondary endpoint:
o CRISS at Week 52, consisting of five variables: mRSS, FVC % predicted, physician and patient global assessments and HAQ-DI score (from SHAQ patient reported outcome)
Further secondary endpoints:
o HAQ-DI domain (separately from SHAQ as part of the calculation of the CRISS algorithm)
o Patient’s global assessment
o Physician’s global assessment
o Change in FVC (forced vital capacity) % predicted

Timepoint(s) of evaluation of this end point: week 52

Secondary ID(s)

BAY63-2521/16277

2014-001353-16-GB

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date:
Contact: