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

NCT02633397 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO15110016
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 20

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).

Conditions

Sickle Cell Disease

Keywords

SCD; Sickle Cell Disease; Riociguat; Adempas

Outcome Measures

Primary Outcomes (1)

• Overall Incidence of Treatment Emergent Severe Adverse Events (SAE)

  The primary endpoint was the proportion of participants who experienced at least 1 treatment-emergent serious adverse event (SAE), which was defined as any event occurring after the baseline visit (i.e., after initiation of study drug), adjudicated by a designated committee of protocol investigators and outside experts. SAEs were considered to be treatment-emergent if they started or worsened after the first dose of study medication and up to 7 days after end of study treatment.

  Baseline through 7 days after discontinuation of treatment, up to 13 Weeks

Secondary Outcomes (22)

• Frequency of SAE Due to Sickle Cell Related Painful Crisis

  Baseline through 7 days after discontinuation of treatment, up to 13 Weeks

• Overall Incidences of Treatment-emergent Adverse Events (AEs)

  Baseline to Week 12

• Incidences of Sickle Cell Related Clinical Complications

  Baseline to Week 12

• Pain Intensity Using the Brief Pain Inventory

  Baseline, 12 weeks

• 6-minute Walk Distance

  Baseline, 12 weeks

Study Arms (2)

Riociguat

EXPERIMENTAL

Treatment Arm

Drug: Riociguat

Placebo

PLACEBO COMPARATOR

Placebo Arm

Drug: Placebo

Interventions

Riociguat 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

Also known as: Adempas

Riociguat

Placebo 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

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mark Gladwin: lead

Study Sites (20)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

University of Illinois, Chicago

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

New York Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11225, United States

Location

Albert Einstein University/ Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UNC Comprehensive Sickle Cell Center

Chapel Hill, North Carolina, 27599-7305, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

UPMC Division of Hematology and Oncology

Pittsburgh, Pennsylvania, 15233, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• 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.

  PMID: 38554715 DERIVED

• 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.

  PMID: 34889382 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

riociguat

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Mark Gladwin
• Organization: Dean, University of Maryland School of Medicine, Vice President for Medical Affairs, University of Maryland, Baltimore

mgladwin@som.umaryland.edu

410-706-7410

Study Officials

• Mark Gladwin, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chariman of the Department of Medicine

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 17, 2015
• Study Start: April 11, 2017
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)