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

NCT ID: NCT02633397

Last Updated: 2023-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-11
• Study Completion Date: 2022-05-04

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).

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.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Riociguat

Treatment Arm

Group Type: EXPERIMENTAL

Riociguat

Intervention Type: DRUG

Riociguat 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg three times a day for 12 weeks

Placebo

Placebo Arm

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Adempas

Eligibility 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, 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mark Gladwin

OTHER

Sponsor Role: lead

Responsible Party

Mark Gladwin

Chariman of the Department of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mark Gladwin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Howard University

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

University of Miami

Miami, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University of Illinois, Chicago

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Tulane University

New Orleans, Louisiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston University Medical Center

Boston, Massachusetts, United States

New York Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, United States

Albert Einstein University/ Montefiore Medical Center

The Bronx, New York, United States

UNC Comprehensive Sickle Cell Center

Chapel Hill, North Carolina, United States

Duke University

Durham, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

UPMC Division of Hematology and Oncology

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Tennessee Health Science Center

Memphis, Tennessee, United States

University of Texas Southwestern

Dallas, Texas, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Countries

United States

References

Gladwin MT, Gordeuk VR, Desai PC, Minniti C, Novelli EM, Morris CR, Ataga KI, De Castro L, Curtis SA, El Rassi F, Ford HJ, Harrington T, Klings ES, Lanzkron S, Liles D, Little J, Nero A, Smith W, Taylor JG 6th, Baptiste A, Hagar W, Kanter J, Kinzie A, Martin T, Rafique A, Telen MJ, Lalama CM, Kato GJ, Abebe KZ. Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial. Lancet Haematol. 2024 May;11(5):e345-e357. doi: 10.1016/S2352-3026(24)00045-0. Epub 2024 Mar 27.

Reference Type: DERIVED

PMID: 38554715 (View on PubMed)

Azbell RCG, Desai PC. Treatment dilemmas: strategies for priapism, chronic leg ulcer disease, and pulmonary hypertension in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):411-417. doi: 10.1182/hematology.2021000275.

Reference Type: DERIVED

PMID: 34889382 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO15110016

Identifier Type: -

Identifier Source: org_study_id