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Trial record 1 of 2 for:    riociguat scleroderma
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Riociguat in Scleroderma Associated Digital Ulcers (RESCUE)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Dinesh Khanna, MD, MS, University of Michigan
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Dinesh Khanna, MD, MS, University of Michigan
ClinicalTrials.gov Identifier:
NCT02915835
First received: September 15, 2016
Last updated: May 9, 2017
Last verified: May 2017
  Purpose
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

Condition Intervention Phase
Scleroderma Digital Ulcers Drug: Riociguat Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center Randomized, Double Blind, Placebo-controlled, Pilot Study to Assess the Efficacy and Safety of Riociguat in Scleroderma - Associated Digital Ulcers

Resource links provided by NLM:


Further study details as provided by Dinesh Khanna, MD, MS, University of Michigan:

Primary Outcome Measures:
  • The primary efficacy outcome is the change from baseline to end of double-blind treatment in digital ulcer net burden. [ Time Frame: Baseline/Week 16 ]
    Digital ulcer net burden is defined as the total number of "new" or "active" digital ulcers at an assessment, plus the number of "indeterminate" ulcers that had previously been classified as either "active" or "new" at any earlier assessment during the study


Secondary Outcome Measures:
  • Healing of cardinal DU [ Time Frame: Baseline/Week 16 ]
    For each participant, one digital ulcer must be identified and designated by the investigator as the cardinal ulcer at Baseline. The cardinal ulcer must have met the qualifications for designation as an active ulcer. If only one ulcer was determined at entry to be active, it will be designated as the cardinal ulcer. If several digital ulcers qualified, the cardinal ulcer could be either the largest or the most painful ulcer, or the ulcer that disturbed the patient the most. The cardinal ulcer will be selected by the investigator based on the clinical judgment that it was amenable to and evaluable for healing.

  • Development of DU [ Time Frame: Baseline/Week 16 ]
  • Development and healing of pressure ulcers over the Distal Interphalangeal (DIP), Proximal Interphalangeal (PIP), Metacarpophalangeal (MCPs) and elbows [ Time Frame: Baseline/Week 16 ]
  • Time to healing of cardinal DU [ Time Frame: Baseline/Week 16 ]
  • Time to healing of all DU [ Time Frame: Baseline/Week 16 ]
  • Improvement of Raynaud's phenomenon (RP) [ Time Frame: Baseline/Week 16 ]
    Improvement in Raynaud's phenomenon will use the composite of the following 6 individual measures: Raynaud's condition score, patient assessment severity of Raynaud's phenomenon, physician assessment severity of Raynaud's phenomenon, severity of attack symptoms from patient diary, duration of attacks from patient diary, and number of attacks per day from patient diary.

  • Patient's and physician's global assessment on a Likert scale [ Time Frame: Baseline/Week 16 ]
  • Health-related quality of life (HRQOL) using PROMIS-29 [ Time Frame: Baseline/Week 16 ]
  • Physical function as assessed by HAQ-DI [ Time Frame: Baseline/Week 16 ]
  • Visual analog scales from scleroderma-health assessment questionnaire (SHAQ) [ Time Frame: Baseline/Week 16 ]
    This Patient Reported Outcome (PRO) will assess the burden of digital ulcers, Raynaud's disease, gastrointestinal involvement, breathing, and overall disease

  • Digital ischemia requiring intravenous prostacyclin or digital gangrene or amputation [ Time Frame: Baseline/Week 16 ]
    These will be collected within Adverse Events

  • Vascular biomarkers in the plasma [ Time Frame: Baseline/Week 16 ]
    Biomarkers: VEGF, tPA, sE-Selectin, BFGF, VCAM-1, ICAM


Estimated Enrollment: 20
Study Start Date: September 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: riociguat
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
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)
Other Name: Adempas
Placebo Comparator: Placebo
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
Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;

Detailed Description:

This clinical trial is a US, multicenter, double-blind, randomized placebo-controlled, parallel- group study with a total of 20 participants planned to be randomized (approximately 10 participants to the riociguat group and 10 to the placebo group). In addition, a standardized wound care protocol will be followed by the investigators and digital photography will be taken of the cardinal ulcer.

The study will allow standard of care medications for the management of DU as background therapy. These may include calcium channel blockers, low dose aspirin, angiotensin enzyme inhibitors, etc. and will be determined by the participant's local physician.

The study design consists of three phases:

  • Screening phase: up to 2 weeks
  • Double-blind Treatment phase: 16 weeks of double-blind treatment, consisting of:
  • Dose titration period of up to 8 weeks, and
  • Stable dosing period of up to 8 weeks
  • Open-label Extension phase for participants with active DU at the end of the double- blind treatment phase or development of an active DU within a month of completing double-blind phase, consisting of:
  • Dose titration phase of up to 8 weeks
  • Stable dosing period for 8 weeks
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. Men or women aged 18 years and older
  3. Diagnosis of Systemic sclerosis, as defined by 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
  4. 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
  5. Females of reproductive potential (FRP) must have a negative, pre-treatment urine pregnancy test.
  6. 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.
  7. 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.)
  8. 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
  9. Ability to comply with the clinical visits schedule and the study-related procedures.

Exclusion Criteria:

  1. Active DU related to calcinosis (as assessed by clinical examination or radiographic evaluation at screening)
  2. 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
  3. Hepatic-related criteria

    - Hepatic insufficiency classified as Child-Pugh C at screening (see Appendix 11.1 for classification table) at screening visit

  4. 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
  5. 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
    • PAH requiring pharmacologic therapy.
    • Significant pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted
  6. Laboratory examinations

    - Participants with hemoglobin < 9.0 g/dL, white blood cell (WBC) count < 3000/mm3 (< 3 × 109/L), platelet count < 100,000/mm3 (< 3 × 109/L) at the screening visit

  7. Prior and concomitant therapy

    • Concomitant use of nitrates or NO donors (such as amyl nitrate) in any form, including topical; phosphodiesterase (PDE) 5 (PDE5) inhibitors (such as sildenafil, tadalafil, vardenafil); and nonspecific PDE5 inhibitors (theophylline,dipyridamole). If the patient is on PDE5 inhibitors, a wash out of 3 days is required for sildenafil and 7 days for tadalafil or vardenafil prior to the baseline visit
    • Concomitant Endothelin receptor antagonist
    • Patients who are actively smoking at time of consent. (Quit date of two weeks prior to screening acceptable)
  8. Pregnant or breastfeeding women
  9. Other

    • Any other condition or therapy that would make the participant unsuitable for this study and will not allow participation for the full planned study period
    • Participation in another clinical study with an investigational drug or medical device within 30 days prior to randomization (phase I-III clinical studies)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02915835

Contacts
Contact: Donna DiFranco 734-764-7374 donnadi@med.umich.edu
Contact: Erica Bush 734-936-5615 ebush@med.umich.edu

Locations
United States, District of Columbia
Georgetown University Recruiting
Washington, D.C., District of Columbia, United States, 20007
Contact: Maia Cecire       mz381@georgetown.edu   
Contact: Jonathan Smith       jds293@georgetown.edu   
Principal Investigator: Virginia Steen, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Aaron Rankin    734-763-4866    rankina@med.umich.edu   
Contact: Erica Bush    734-845-1771    ebush@med.umich.edu   
Principal Investigator: Dinesh Khanna, MD         
United States, New York
Hospital of Special Surgery (HSS) Recruiting
New York, New York, United States, 10035
Contact: Emily Bakaj    212-774-7620    bakaje@hss.edu   
Contact: Eileen McCullagh    212-774-7381    mccullaghe@hss.edu   
Principal Investigator: Jessica Gordon, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Dana Ivanco    412-648-7040    des2@pitt.edu   
Contact: Maureen Laffoon       laffoonm@pitt.edu   
Principal Investigator: Robyn T Domsic, MD MPH         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Nadia Hamad       Nadia.hamad@hsc.utah.edu   
Contact: Martha Finco       Martha.Finco@hsc.utah.edu   
Principal Investigator: Tracy Frech, MD         
Sponsors and Collaborators
Dinesh Khanna, MD, MS
Bayer
Investigators
Principal Investigator: Dinesh Khanna, MD University of Michigan
  More Information

Responsible Party: Dinesh Khanna, MD, MS, Professor of Rheumatology/ Internal Medicine, University of Michigan
ClinicalTrials.gov Identifier: NCT02915835     History of Changes
Other Study ID Numbers: BAY63-2521
Study First Received: September 15, 2016
Last Updated: May 9, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Dinesh Khanna, MD, MS, University of Michigan:
Scleroderma
Digital Ulcer

Additional relevant MeSH terms:
Ulcer
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Skin Ulcer
Pathologic Processes
Connective Tissue Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 18, 2017