A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)
- Registration Number
- NCT03924154
- Lead Sponsor
- Altavant Sciences GmbH
- Brief Summary
This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).
- Detailed Description
This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).
Study participation for each patient will last approximately 3 months and will consist of a screening period (up to 28 days in duration), a baseline period (day 1, pre-dose), a 6-week treatment period, and a 2-week follow-up period.
The study will enroll approximately 36 patients at approximately 20 centers across the United States and Canada.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
-
Symptomatic PAH belonging to one of the following types:
- Idiopathic
- Heritable
- Drug- or toxin- induced
- Associated with one of the following: connective tissue disease or congenital heart disease
-
World Health Organization (WHO) Functional Class (FC) II or III
-
PAH diagnosed by right heart cardiac catheterization prior to Screening
-
Receiving standard of care treatment for PAH with oral monotherapy or dual therapy for at least 12 weeks prior to Screening at a dose which has been stable for at least 8 weeks prior to Screening
-
If on a diuretic, dose must be stable for at least 4 weeks prior to Screening, with no changes anticipated during study participation
-
6-Minute Walk Distance (6MWD) between 150 and 500 meters at Screening and Baseline visits
-
Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) level ≥ 300 pg/mL at Screening
-
Ability and willingness to give written informed consent and to comply with the requirements of the study
Key
-
PAH associated with human immunodeficiency virus (HIV) infection, portal hypertension or schistosomiasis
-
Other types of pulmonary hypertension (PH):
- Pulmonary hypertension due to left heart disease (WHO PH Group 2)
- Pulmonary hypertension due to lung diseases and/or hypoxia (WHO PH Group 3)
- Chronic thromboembolic pulmonary hypertension (WHO PH Group 4)
- Pulmonary hypertension with unclear multifactorial mechanisms (WHO PH Group 5)
-
Hospitalization for pulmonary hypertension within 12 weeks of screening
-
Cardiopulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Screening)
-
Prostanoid or prostacyclin receptor agonist therapy within 12 weeks of screening
-
Evidence of left-sided heart disease
-
If Pulmonary function tests were done prior to screening, Pulmonary function tests demonstrate obstructive or restrictive lung disease
-
Use of telotristat (Xermelo®) within the last 6 months
-
Use of any investigational drug within 30 days or five half-lives (whichever is longer) prior to Screening, or 90 days if an investigational drug for PAH
-
Have uncontrolled atrial fibrillation (AFib) or other uncontrolled arrhythmias
-
Body mass index (BMI) >45 kg/m2
-
Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching placebo tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=12 \[Anticipated\]) RVT-1201 RVT-1201 RVT-1201 600 mg immediate-release tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=24 \[Anticipated\])
- Primary Outcome Measures
Name Time Method Adverse events (AEs) and discontinuations due to AEs 8 weeks Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs
- Secondary Outcome Measures
Name Time Method Concentration of biomarkers of serotonin biosynthesis in urine 8 weeks Concentration of urine 5-hydroxyindoleacetic acid (5-HIAA) will be normalized against urine creatinine concentration to determine absolute ratio and percent change from baseline in urine 5-HIAA:creatinine ratio
Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201) 6 weeks Measured KAR5417 plasma concentrations from sparse sampling will be used to assess the pharmacokinetic (PK) parameter AUC of KAR5417 administered twice daily in patients with PAH, by means of population PK (PopPK) analysis
Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers 6 weeks Evaluate the relationship between exposure (area under the plasma concentration versus time curve \[AUC\]) of KAR5417 (the active metabolite of RVT-1201) and percent change from baseline in plasma concentrations of the serotonin-related biomarkers (5-HIAA and 5-HT)
Concentration of biomarkers of serotonin biosynthesis in plasma 8 weeks Absolute concentrations and percent change from baseline in plasma 5-hydroxyindoleacetic acid (5-HIAA) and plasma 5-hydroxytryptamine (5-HT, also known as serotonin) concentrations
Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations 6 weeks Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling
Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers 6 weeks Evaluate the relationship between exposure (area under the plasma concentration versus time curve \[AUC\]) of KAR5417 (the active metabolite of RVT-1201) and percent change from baseline in urine 5-HIAA:creatinine concentration ratio
Trial Locations
- Locations (23)
SBPA Research LLC
🇺🇸Santa Barbara, California, United States
Kentuckiana Pulmonary Research Center
🇺🇸Louisville, Kentucky, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
San Marcus Research Clinic, Inc.
🇺🇸Miami Lakes, Florida, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Central Florida Pulmonary Group, P.A.
🇺🇸Orlando, Florida, United States
Pulmonary Research Institute of Southeast Michigan
🇺🇸Farmington Hills, Michigan, United States
University of Texas Health Science Center at Houston, McGovern Medical School
🇺🇸Houston, Texas, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
University of Florida
🇺🇸Gainesville, Florida, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Pulmonary Associates, PA
🇺🇸Phoenix, Arizona, United States
George Washington Medical Faculty Associates - Pulmonary Hypertension Program
🇺🇸Washington, District of Columbia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Louisiana State University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States