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A Multi-Center Study of Riociguat in Patients With Sickle Cell Diseases

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ClinicalTrials.gov Identifier: NCT02633397
Recruitment Status : Recruiting
First Posted : December 17, 2015
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gregory J. Kato, MD, University of Pittsburgh

Brief Summary:
The proposed study is a Phase 2 multi-center, randomized, double-blind, placebo-controlled, parallel groups study aimed to evaluate the safety, tolerability and the efficacy of riociguat compared with placebo in patients with sickle cell disease (SCD).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Riociguat Drug: Placebo Phase 2

Detailed Description:
This randomized study involves 12 weeks of treatment with riociguat pills or placebo pills, and a follow-up period of 30 days after treatment. The dose is adjusted every 2 weeks based on systolic blood pressure (SBP) and well-being assessed at that visit. Physical examinations, vital signs, blood tests and questionnaires will be performed at 2 week intervals during the double blinded study treatment. Echocardiogram, urine testing, six-minute walk distance and questionnaires will be assessed at the beginning and end of the treatment phase.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-Blind, Placebo-Controlled Multi-Center Study to Assess the Safety, Tolerability, and Efficacy of Riociguat in Patients With Sickle Cell Diseases
Actual Study Start Date : April 11, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Riociguat
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Riociguat
Treatment Arm
Drug: Riociguat
Riociguat 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg three times a day for 12 weeks
Other Name: Adempas
Placebo Comparator: Placebo
Placebo Arm
Drug: Placebo
Matching placebo to riociguat 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg three times a day for 12 weeks



Primary Outcome Measures :
  1. Overall incidence of treatment emergent severe adverse events (SAE) [ Time Frame: Baseline to Week 12 ]

Secondary Outcome Measures :
  1. Frequency of SAE due to sickle cell related painful crisis [ Time Frame: Baseline to Week 12 ]
  2. Overall incidences of treatment-emergent adverse events (AEs) [ Time Frame: Baseline to Week 12 ]
  3. Changes in pain intensity using numerical pain score [ Time Frame: Baseline to Week 12 ]
  4. Changes in functional exercise capacity by assessing 6 minute walk distance test [ Time Frame: Baseline to Week 12 ]
  5. Changes in blood pressure as the main pharmacodynamic variable [ Time Frame: Baseline to Week 12 ]
  6. Changes in the levels of plasma NT-proBNP [ Time Frame: Baseline to Week 12 ]
  7. Changes in the Modified Borg Dyspnoea Scale [ Time Frame: Baseline to Week 12 ]
  8. Changes in laboratory measures [ Time Frame: Baseline to Week 12 ]
  9. Incidences of sickle cell related clinical complications [ Time Frame: Baseline to Week 12 ]
  10. Changes in tricuspid regurgitant velocity using non-invasive echocardiography [ Time Frame: Baseline to Week 12 ]
  11. Changes in pain intensity using the Brief Pain Inventory [ Time Frame: Baseline to Week 12 ]
  12. Changes in pain intensity using electronic daily pain diary piloted at selected sites [ Time Frame: Baseline to Week 12 ]


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

Inclusion Criteria:

  • Age ≥ 18 years
  • Sickling disorder (HbSS, HbSC, HbSbeta-thalassemia, HbSD, HbSO-Arab documented by hemoglobin electrophoresis or HPLC fractionation)
  • At least one of the following findings: a. Systolic blood pressure ≥ 130 mm Hg on at least two occasions at least 1 day apart (one of these may be by history), b. Macroalbuminuria as manifested by urine albumin to creatinine ratio > 300 mg/g, c. Tricuspid regurgitant velocity (TRV) > 2.9 m/sec measured by echocardiography d. NT-proBNP level ≥ 160 pg/mL e. Urinalysis protein 1 + or higher.
  • Females of reproductive potential (FRP) must have a negative, pre-treatment pregnancy test. 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.
  • Females of reproductive potential must agree to use reliable contraception when sexually active. 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). Adequate contraception is required beginning at the signing of the informed consent form until one month after the last dose of riociguat.
  • Patients must be willing to provide a blood sample for DNA analysis.

Exclusion Criteria:

  • Pregnant or breast feeding women
  • Patients with severe hepatic impairment defined as Child Pugh C
  • End stage renal disease requiring dialysis
  • Patients with eGFR <30 mL/min/1.73m, where GFR is estimated based on CKD-epi equation
  • Patients on phosphodiesterase type 5 inhibitors (PDE-5) (such as sildenafil, tadalafil, vardenafil) and nonspecific PDE inhibitors (such as dipyridamole or theophylline) or nitrates
  • Patients on strong cytochrome P450 (CYP) and P-glycoprotein 1(P-gp)/BCRP inhibitors such as systemic azole antimycotics (eg: ketoconazole, itraconazole), or HIV protease inhibitors (such as ritonavir)
  • Patients on St. John's Wort
  • If patients are taking antihypertensive drugs or hydroxyurea prior to enrollment, they are excluded until the dose level is stable for at least three months
  • Systolic blood pressure <95 mm Hg at Screening Visit 1 or 2 or Week 0 before randomization
  • Current enrollment in an investigational new drug trial. Patients are eligible for enrollment 30 days after the last dose of an investigational drug has been received
  • Evidence of illicit drug use as documented by a positive urine toxicology screen within three months prior to enrollment
  • Patients who have recently (last six months) experienced serious bleeding from the lung or have undergone a bronchial arterial embolization procedure.
  • Pulmonary hypertension associated with Idiopathic Interstitial Pneumonias
  • Medical disorder, condition, or history that in the investigator's judgement would impair the patient's ability to participate or complete this study or render the patient to be inappropriate for enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02633397


Contacts
Contact: Gregory Kato, MD 412-648-3017 katogj@upmc.edu
Contact: Carolyn Newkirk, MEd 412-692-2437 can59@pitt.edu

Locations
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30329
Contact: Claudia Morris, MD    404-727-5500    claudia.r.morris@emory.edu   
Contact: April Zmitrovich    404-785-7135    april.zmitrovich@choa.org   
Principal Investigator: Claudia Morris, MD         
United States, Illinois
University of Illinois, Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Victor R Gordeuk, MD    312-996-5680    vgordeuk@uic.edu   
Contact: Aprille Mae Simbulan    312-996-8767    asimbu2@uic.edu   
Principal Investigator: Victor R Gordeuk, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
Contact: Sophie Lanzkron, MD, MHS    410-502-8642 ext 3    slanzkr@jhmi.edu   
Contact: Cedron Williams    410-502-6593    Cwill116@jhmi.edu   
United States, New York
Albert Einstein University/ Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Caterina Minniti, M.D.    718-920-4137    cminniti@montefiore.org   
Contact: Kelsey Branch       kebranch@montefiore.org   
Principal Investigator: Caterina Minniti, MD         
United States, North Carolina
UNC Comprehensive Sickle Cell Center Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
Contact: Kenneth Ataga, MD    919-843-7708    kenneth_ataga@med.unc.edu   
Contact: David Wichlan    919-966-6876    david_wichlan@med.unc.edu   
Principal Investigator: Kenneth Ataga, MD         
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Marilyn Telen, MD    919-684-5378    marilyn.telen@duke.edu   
Contact: Angela Brasswell    919-681-8645    angela.braswell@duke.edu   
Principal Investigator: Marilyn Telen, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Payal Desai, MD    614-293-2887    Payal.Desai@osumc.edu   
Contact: Melanie Heinlein    614-293-5176    Melanie.Heinlein@osumc.edu   
Principal Investigator: Payal Desai, MD         
United States, Pennsylvania
UPMC Division of Hematology and Oncology Recruiting
Pittsburgh, Pennsylvania, United States, 15233
Contact: Laura DeCastro, MD    412-623-7062    decastrolm@upmc.edu   
Contact: Jude Jonassaint, RN    412-623-1100    jonassaintjc@upmc.edu   
Principal Investigator: Laura DeCastro, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Julie Kanter, MD    843-792-2957    kanter@musc.edu   
Contact: Cheryl Alston    843-876-8652    alstonch@musc.edu   
Principal Investigator: Julie Kanter, MD         
United States, Virginia
Virginia Commonwealth University Medical Center Recruiting
Richmond, Virginia, United States, 23298
Contact: Wally Smith, M.D.    804-828-6938    wrsmith@vcu.edu   
Contact: Daniel Sop    804-828-0810    daniel.sop@vcuhealth.org   
Principal Investigator: Wally Smith, M.D.         
Sponsors and Collaborators
Gregory J. Kato, MD
Investigators
Principal Investigator: Gregory Kato, MD University of Pittsburgh

Responsible Party: Gregory J. Kato, MD, Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02633397     History of Changes
Other Study ID Numbers: PRO15110016
First Posted: December 17, 2015    Key Record Dates
Last Update Posted: May 16, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gregory J. Kato, MD, University of Pittsburgh:
SCD
Sickle Cell Disease
Riociguat
Adempas

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn