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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RVT-1201
Placebo
Sponsored by
Altavant Sciences GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary arterial hypertension (PAH), Pulmonary hypertension (PH), RVT-1201, Rodatristat ethyl, Tryptophan hydroxylase (TPH), Serotonin reduction, ELEVATE 1, KAR5417

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pulmonary Associates, PA
  • University of California Davis Medical Center
  • SBPA Research LLC
  • University of Colorado
  • George Washington Medical Faculty Associates - Pulmonary Hypertension Program
  • University of Florida
  • San Marcus Research Clinic, Inc.
  • Central Florida Pulmonary Group, P.A.
  • University of Chicago Medical Center
  • Kentuckiana Pulmonary Research Center
  • Louisiana State University Health Sciences Center
  • Boston Children's Hospital
  • Baystate Medical Center
  • Pulmonary Research Institute of Southeast Michigan
  • Washington University School of Medicine
  • Duke University Medical Center
  • Cleveland Clinic
  • Oregon Health & Science University
  • University of Texas Southwestern Medical Center
  • University of Texas Health Science Center at Houston, McGovern Medical School
  • University of Calgary
  • University of Alberta
  • London Health Sciences Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RVT-1201

Placebo

Arm Description

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])

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])

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations
Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling
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
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)
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

Full Information

First Posted
April 5, 2019
Last Updated
March 5, 2020
Sponsor
Altavant Sciences GmbH
Collaborators
Altavant Sciences, Inc., PPD
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1. Study Identification

Unique Protocol Identification Number
NCT03924154
Brief Title
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

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Inability to enroll
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
February 24, 2020 (Actual)
Study Completion Date
February 24, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Altavant Sciences GmbH
Collaborators
Altavant Sciences, Inc., PPD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary arterial hypertension (PAH), Pulmonary hypertension (PH), RVT-1201, Rodatristat ethyl, Tryptophan hydroxylase (TPH), Serotonin reduction, ELEVATE 1, KAR5417

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RVT-1201
Arm Type
Experimental
Arm Description
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])
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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])
Intervention Type
Drug
Intervention Name(s)
RVT-1201
Other Intervention Name(s)
rodatristat ethyl
Intervention Description
RVT-1201 600 mg immediate-release tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for RVT-1201)
Intervention Description
Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet
Primary Outcome Measure Information:
Title
Adverse events (AEs) and discontinuations due to AEs
Description
Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Concentration of biomarkers of serotonin biosynthesis in plasma
Description
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
Time Frame
8 weeks
Title
Concentration of biomarkers of serotonin biosynthesis in urine
Description
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
Time Frame
8 weeks
Title
Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations
Description
Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling
Time Frame
6 weeks
Title
Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)
Description
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
Time Frame
6 weeks
Title
Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers
Description
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)
Time Frame
6 weeks
Title
Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers
Description
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
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ed Parsley, DO
Organizational Affiliation
Altavant Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Pulmonary Associates, PA
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
SBPA Research LLC
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
George Washington Medical Faculty Associates - Pulmonary Hypertension Program
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
San Marcus Research Clinic, Inc.
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Central Florida Pulmonary Group, P.A.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Kentuckiana Pulmonary Research Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Louisiana State University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Pulmonary Research Institute of Southeast Michigan
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48336
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas Health Science Center at Houston, McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T1Y6J4
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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

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