A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)

NCT03924154 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: RVT-1201-2001
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 23

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).

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension (PAH); Pulmonary hypertension (PH); RVT-1201; Rodatristat ethyl; Tryptophan hydroxylase (TPH); Serotonin reduction; ELEVATE 1; KAR5417

Outcome Measures

Primary Outcomes (1)

• Adverse events (AEs) and discontinuations due to AEs

  Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs

  8 weeks

Secondary Outcomes (6)

• Concentration of biomarkers of serotonin biosynthesis in plasma

  8 weeks

• Concentration of biomarkers of serotonin biosynthesis in urine

  8 weeks

• Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations

  6 weeks

• Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)

  6 weeks

• Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers

  6 weeks

Study Arms (2)

RVT-1201

EXPERIMENTAL

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 \[Anticipated\])

Drug: RVT-1201

Placebo

PLACEBO COMPARATOR

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 \[Anticipated\])

Drug: Placebo

Interventions

RVT-1201 DRUG

RVT-1201 600 mg immediate-release tablet

Also known as: rodatristat ethyl

RVT-1201

Placebo DRUG

Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet

Also known as: Placebo (for RVT-1201)

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Altavant Sciences GmbH: lead
• Altavant Sciences, Inc.: collaborator
• PPD Development, LP: collaborator

Study Sites (23)

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

SBPA Research LLC

Santa Barbara, California, 93105, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

George Washington Medical Faculty Associates - Pulmonary Hypertension Program

Washington D.C., District of Columbia, 20037, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, 33014, United States

Location

Central Florida Pulmonary Group, P.A.

Orlando, Florida, 32803, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, 40202, United States

Location

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Pulmonary Research Institute of Southeast Michigan

Farmington Hills, Michigan, 48336, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas Health Science Center at Houston, McGovern Medical School

Houston, Texas, 77030, United States

Location

University of Calgary

Calgary, Alberta, T1Y6J4, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

rodatristat

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ed Parsley, DO

  Altavant Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 23, 2019
• Study Start: August 1, 2019
• Primary Completion: February 24, 2020
• Study Completion: February 24, 2020
• Last Updated: March 9, 2020

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (20)