Overview

This trial is active, not recruiting.

Condition sickle cell disease
Treatments riociguat, placebo
Phase phase 2
Sponsor Gregory J. Kato, MD
Start date July 2016
End date December 2018
Trial size 100 participants
Trial identifier NCT02633397, PRO15110016

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 SCD.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Treatment Arm
riociguat Adempas
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 Comparator)
Placebo Arm
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 Outcomes

Measure
Overall incidence of treatment emergent SAE
time frame: Baseline to Week 12

Secondary Outcomes

Measure
Frequency of SAE due to sickle cell related painful crisis
time frame: Baseline to Week 12
Overall incidences of treatment-emergent AEs
time frame: Baseline to Week 12
Changes in pain intensity using numerical pain score
time frame: Baseline to Week 12
Changes in functional exercise capacity by assessing 6 minute walk distance test
time frame: Baseline to Week 12
Changes in blood pressure as the main pharmacodynamic variable
time frame: Baseline to Week 12
Changes in the levels of plasma NT-proBNP
time frame: Baseline to Week 12
Changes in the Modified Borg Dyspnoea Scale
time frame: Baseline to Week 12
Changes in laboratory measures
time frame: Baseline to Week 12
Incidences of Sickle Cell related clinical complications
time frame: Baseline to Week 12
Changes in tricuspid regurgitant velocity using an invasive transthoracic echocardiography
time frame: Baseline to Week 12
Changes in pain intensity using the Brief Pain Inventory
time frame: Baseline to Week 12
Changes in pain intensity using electronic daily pain diary piloted at selected sites
time frame: Baseline to Week 12

Eligibility Criteria

Male or female participants at least 18 years old.

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 - 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 - Active smoking of tobacco of any type or quantity - 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 MDRD equation or creatinine clearance <30ml/min estimated by the Cockcroft-Gault 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 or 5 half-lives, whatever is longer, 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 - 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

Additional Information

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
Principal investigator Gregory Kato, MD
Description The study will consist of a screening epoch, a 12 week double blinded treatment epoch, and a follow-up epoch of 30 days post treatment. Following completion of screening and baseline assessment, patients who meet all the inclusion and none of the exclusion criteria will be randomized on a 1:1 basis to receive either placebo or riociguat at the starting dose of 1.0 mg TID (three times a day) for 12 weeks. The dose will be titrated every 2 weeks based on patient's monitoring of systolic blood pressure (SBP) and well-being assessed at that visit. Safety monitoring including physical examinations, hemodynamics, vital signs, clinical laboratory assessment will be conducted at 2 week intervals during the double blinded study treatment. Safety and tolerability, especially pain, will be assessed using several specific patient reported outcome instruments. Functional outcomes measuring the changes in six minute walk distances and Borg Dyspnea Scores will be assessed from baseline to Week 12.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by University of Pittsburgh.