Clinical trial NCT03924154: A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)
Official title: A Phase 2a, Double-Blind, Placebo-Controlled Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of RVT-1201 in Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary arterial hypertension (PAH)
Pulmonary hypertension (PH)
RVT-1201
Rodatristat ethyl
Tryptophan hydroxylase (TPH)
Serotonin reduction
ELEVATE 1
KAR5417
Lead sponsor: Altavant Sciences GmbH
Sponsor class: INDUSTRY
Collaborators: name: Altavant Sciences, Inc.
name: PPD Development, LP
First posted: 2019-04-23
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Following screening assessments, PAH patients who meet all entrance criteria will be randomly assigned to receive one of the following treatments in a ratio of 2:1:

* Arm 1 (n=24) - RVT-1201 Treatment: RVT-1201 immediate-release tablets will be administered orally, at a dose of 600 mg twice daily (BID), for a total of 6 weeks in addition to the patient's current standard of care (SOC) medication(s) for PAH.
* Arm 2 (n=12) - Placebo Treatment: Matching placebo tablets will be administered orally, at a dose of 600 mg twice daily (BID), for a total of 6 weeks in addition to the patient's current SOC medication(s) for PAH.

Participants will be followed in face-to-face visits with trial personnel every 2 weeks for 8 weeks (6 weeks of treatment plus a 2-week follow-up), with an additional phone call at Week 1, to assess drug effects and monitor safety during their treatments.
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Adverse events (AEs) and discontinuations due to AEs
timeFrame: 8 weeks
Secondary outcomes:
measure: Concentration of biomarkers of serotonin biosynthesis in plasma
timeFrame: 8 weeks
measure: Concentration of biomarkers of serotonin biosynthesis in urine
timeFrame: 8 weeks
measure: Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations
timeFrame: 6 weeks
measure: Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)
timeFrame: 6 weeks
measure: Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers
timeFrame: 6 weeks
measure: Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Santa Barbara
country: United States
facility: SBPA Research LLC
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: George Washington Medical Faculty Associates - Pulmonary Hypertension Program
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, P.A.
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Research Center
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Pulmonary Research Institute of Southeast Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston, McGovern Medical School
state: Texas
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Altavant Sciences
name: Ed Parsley, DO
role: STUDY_DIRECTOR
References: