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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-001353-16-ES
• Date of registration: 03/11/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare 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: 22/12/2014
• 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 HealthCare AG

• Name: Clinical Trials Contact
• Affiliation: Bayer HealthCare 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
5. Disease duration of <= 18 months (defined as time from the first non-Raynauds 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
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
- 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. Diagnosed PAH 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. Any history of bronchial artery emolization or massive hemoptysis within 3 months, before screening.
13. Not permitted prior and concomitant medication
14. pregnant or breast feeding women
15. 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

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

diffuse cutaneous systemic sclerosis (dcSSc)
MedDRA version: 17.1 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859

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: riociguat coated tablet 2.0 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: 2.0-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Adempas
Product Name: riociguat coated tablet 2.5 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
Concentrati

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.

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

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

Secondary Objective: The secondary objectives of this study are to assess the efficacy of treatment with riociguat administered TID as compared with placebo in terms of:
o mRSS progression rate (defined as increase in mRSS by > 5 units and ? 25% from baseline) and mRSS regression rate (defined as decrease in mRSS by > 5 units and ? 25% from baseline)
o Patient?s and physician?s global assessment
o HRQoL using Short Form 36 (SF-36) and the Scleroderma Health Assessment Questionnaire (SHAQ)
o Digital ulcer net burden (defined as total number of ulcers at time point minus number of ulcers at baseline) and proportion of patients who do not develop new ulcers
o Change in FVC (forced vital capacity) % predicted and percent DLCO (carbon monoxide diffusing capacity) % predicted
o Combined Response Index for Systemic Sclerosis (CRISS)
o Need for Escape Therapy

Secondary Outcome(s)

Secondary end point(s): o mRSS progression rate (defined as increase in mRSS by > 5 units and > 25% from baseline) and mRSS regression rate (defined as decrease in mRSS by > 5 units and > 25% from baseline)
o Patient´s and physician´s global assessment
o HRQoL using SF-36 and the SHAQ
o Digital ulcer net burden (defined as total number of ulcers at time point minus number of ulcers at baseline) and proportion of patients who do not develop new ulcers
o Change in FVC (forced vital capacity) % predicted and DLCO (carbon monoxide diffusing capacity) % predicted
o Combined Response Index for Systemic Sclerosis (CRISS), consisting of five variables: mRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score (from SHAQ patient reported outcome)
o Need for Escape Therapy

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

Secondary ID(s)

2014-001353-16-GB

BAY63-2521/16277

Source(s) of Monetary Support

Bayer HealthCare AG

Ethics review

Status: Approved
Approval date:
Contact: