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

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

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 Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: RVT-1201; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y6J4
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Santa Barbara, California, United States, 93105
      • SBPA Research LLC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates - Pulmonary Hypertension Program
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, P.A.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Pulmonary Research Institute of Southeast Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston, McGovern Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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])	Drug: RVT-1201; RVT-1201 600 mg immediate-release tablet; Other Names: rodatristat ethyl
Placebo Comparator: 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])	Drug: Placebo; Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet; Other Names: Placebo (for RVT-1201)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of biomarkers of serotonin biosynthesis in plasma	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	8 weeks
Concentration of biomarkers of serotonin biosynthesis in urine	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	8 weeks
Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations	Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling	6 weeks
Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)	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	6 weeks
Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers	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)	6 weeks
Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers	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	6 weeks

Collaborators and Investigators

• Sponsor: Altavant Sciences GmbH
• Collaborators: PPD; Altavant Sciences, Inc.
• Investigators: Study Director: Ed Parsley, DO, Altavant Sciences

Publications and helpful links

Helpful Links

• RVT-1201-2001 (ELEVATE 1) study website

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): February 24, 2020
• Study Completion (Actual): February 24, 2020

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 9, 2020
• Last Update Submitted That Met QC Criteria: March 5, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary hypertension (PH); Pulmonary arterial hypertension (PAH); RVT-1201; Rodatristat ethyl; Tryptophan hydroxylase (TPH); Serotonin reduction; ELEVATE 1; KAR5417
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: RVT-1201-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No