Riociguat in Scleroderma Associated Digital Ulcers

NCT02915835 | Completed Phase 2 Results DMC

• 1 other identifier: BAY63-2521
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of this study is to provide preliminary data on the efficacy (digital ulcer net burden) and safety of riociguat administered 3 times daily (TID) in comparison to placebo in patients with scleroderma-associated digital ulcers

Conditions

Scleroderma; Digital Ulcers

Keywords

Scleroderma; Digital Ulcer

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to End of Double-blind Treatment (Week 16) in Digital Ulcer Net Burden

  Digital ulcer net burden is defined as the total number of "active" and indeterminate digital ulcers at an assessment. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.

  Baseline to Week 16

Secondary Outcomes (59)

• Proportion of Participants With Healing of Their Cardinal DU by Week 16

  Week 16

• Proportion of Participants With Healing of All DUs at Baseline by Week 16

  Week 16

• Proportion of Participants With no DUs at Week 16

  Week 16

• Proportion of Participants With New Active and Indeterminate DU(s) Over the Course of the Double-blind Period

  Baseline to Week 16

• Proportion of Participants Who Develop Pressure Ulcers at Distal Interphalangeal (DIP) Location Over the Course of the Double-blind Period.

  Baseline to Week 16

Study Arms (2)

riociguat

ACTIVE COMPARATOR

Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)

Drug: Riociguat

Placebo

PLACEBO COMPARATOR

Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.

Drug: Placebo

Interventions

Riociguat DRUG

riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)

Also known as: Adempas

riociguat

Placebo DRUG

Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Men or women aged 18 years and older
• Diagnosis of Systemic sclerosis, as defined by 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
• Patients had to have at least one visible, active ischemic DU at baseline located at or distal to the proximal interphalangeal joint, and that developed or worsened within 8 weeks prior to screening. NOTE: Presence of eschar will not be considered an active ulcer
• Females of reproductive potential (FRP) must have a negative, pre-treatment urine pregnancy test.
• FRP must obtain monthly urine pregnancy tests during treatment and one month after treatment discontinuation. Post-menopausal women (defined as no menses for at least 1 year or post-surgical from bilateral oophorectomy) are not required to undergo a pregnancy test.
• FRP and all non-vasectomized male participants must agree to use reliable contraception when sexually active. (For FRP's, 'Adequate contraception' is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g., condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). This applies from the time of signing the informed consent form until one month after the last study drug administration.)
• Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent), nonsteroidal anti- inflammatory drugs (NSAIDs), angiotensin receptor blockers, angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers are permitted if the participant is on a stable dose for ≥ 2 weeks prior to and including the baseline visit
• Ability to comply with the clinical visits schedule and the study-related procedures.

You may not qualify if:

• Active DU related to calcinosis (as assessed by clinical examination or radiographic evaluation at screening)
• Medical and surgical history
• Major surgery (including joint surgery) within 8 weeks prior to screening
• Participants with a history of malignancy in the last 5 years other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
• Hepatic-related criteria
• \- Hepatic insufficiency classified as Child-Pugh C at screening (see Appendix 11.1 for classification table) at screening visit
• Renal-related criteria
• Estimated glomerular filtration rate (eGFR) \< 15 mL/min/1.73m2 (MDRD formula) or on dialysis at the screening visit
• Cardiovascular-related criteria
• Sitting systolic blood pressure \< 95 mmHg at the screening visit
• Sitting heart rate \< 50 beats per minute (BPM) at the screening visit
• Left ventricular ejection fraction \< 40% prior to screening on echocardiogram done as part of clinical care
• Pulmonary-related criteria
• Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
• Any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening. Massive hemoptysis being defined as acute bleeding \>240 mL in a 24-hour period or recurrent bleeding \>100 mL/d over several days

Sponsors & Collaborators

• Dinesh Khanna, MD, MS: lead
• Bayer: collaborator

Study Sites (5)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Hospital of Special Surgery (HSS)

New York, New York, 10035, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Nagaraja V, Spino C, Bush E, Tsou PS, Domsic RT, Lafyatis R, Frech T, Gordon JK, Steen VD, Khanna D. A multicenter randomized, double-blind, placebo-controlled pilot study to assess the efficacy and safety of riociguat in systemic sclerosis-associated digital ulcers. Arthritis Res Ther. 2019 Sep 3;21(1):202. doi: 10.1186/s13075-019-1979-7.

  PMID: 31481106 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse; digital ulcers

Interventions

riociguat

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Dr. Cathie Spino
• Organization: University of Michigan

spino@umich.edu

7346155469

Study Officials

• Dinesh Khanna, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Rheumatology/ Internal Medicine

Study Record Dates

• First Submitted: September 15, 2016
• First Posted: September 27, 2016
• Study Start: September 1, 2016
• Primary Completion: July 24, 2018
• Study Completion: July 24, 2018
• Last Updated: September 24, 2019
• Results First Posted: September 24, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)