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

Study point of contact

Carolyn Newkirk, MEd
412-692-2437
[email protected]
Mark Gladwin, MD
412-648-9641
[email protected]

Locations

20 United States sites

Age

> 18 Years

Genotypes

HbSS, HbSC

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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).

participation requirements

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.

participation restrictions

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, hydroxyurea, L-glutamine, crizanlizumab, or voxelotor 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 qualitative urine drug test at screening for cocaine, phencyclidine (PCP), heroin, or amphetamines 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 judgment would impair the patient's ability to participate or complete this study or render the patient to be inappropriate for enrollment

Locations

  • Oakland, California, United States, UCSF Benioff Children's Hospital Oakland, 94609 [Recruiting]
  • Washington, District of Columbia, United States, Howard University, 20060 [Recruiting]
  • Miami, Florida, United States, University of Miami, 33136 [Recruiting]
  • Atlanta, Georgia, United States, Emory University School of Medicine, 30329 [Recruiting]
  • Chicago, Illinois, United States, University of Illinois, Chicago, 60612 [Recruiting]
  • Indianapolis, Indiana, United States, Indiana University, 46202 [Recruiting]
  • New Orleans, Louisiana, United States, Tulane University, 70112 [Recruiting]
  • Baltimore, Maryland, United States, Johns Hopkins University, 21205 [Recruiting]
  • Boston, Massachusetts, United States, Boston University Medical Center, 02118 [Recruiting]
  • Bronx, New York, United States, Albert Einstein University/ Montefiore Medical Center, 10467 [Recruiting]
  • Brooklyn, New York, United States, New York Presbyterian Brooklyn Methodist Hospital, 11225 [Recruiting]
  • Chapel Hill, North Carolina, United States, UNC Comprehensive Sickle Cell Center, 27599-7305 [Recruiting]
  • Durham, North Carolina, United States, Duke University, 27710 [Recruiting]
  • Greenville, North Carolina, United States, East Carolina University, 27834 [Recruiting]
  • Columbus, Ohio, United States, Ohio State University, 43210 [Recruiting]
  • Pittsburgh, Pennsylvania, United States, UPMC Division of Hematology and Oncology, 15233 [Recruiting]
  • Charleston, South Carolina, United States, Medical University of South Carolina, 29425 [Recruiting]
  • Memphis, Tennessee, United States, University of Tennessee Health Science Center, 38163 [Recruiting]
  • Dallas, Texas, United States, University of Texas Southwestern, 75390 [Recruiting]
  • Richmond, Virginia, United States, Virginia Commonwealth University Medical Center, 23298 [Recruiting]
Last updated 2021-07-19 Enroll Now