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Trial record 1 of 51844 for:    ELEVATE 1
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A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)

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ClinicalTrials.gov Identifier: NCT03924154
Recruitment Status : Terminated (Inability to enroll)
First Posted : April 23, 2019
Last Update Posted : March 9, 2020
Sponsor:
Collaborators:
Altavant Sciences, Inc.
PPD
Information provided by (Responsible Party):
Altavant Sciences GmbH

Study Description
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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).

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: RVT-1201 Drug: Placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 1, 2019
Actual Primary Completion Date : February 24, 2020
Actual Study Completion Date : February 24, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Placebo (for RVT-1201)


Outcome Measures
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Primary Outcome Measures :
  1. Adverse events (AEs) and discontinuations due to AEs [ Time Frame: 8 weeks ]
    Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs


Secondary Outcome Measures :
  1. Concentration of biomarkers of serotonin biosynthesis in plasma [ Time Frame: 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

  2. Concentration of biomarkers of serotonin biosynthesis in urine [ Time Frame: 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

  3. Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations [ Time Frame: 6 weeks ]
    Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling

  4. Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201) [ Time Frame: 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

  5. Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers [ Time Frame: 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)

  6. Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers [ Time Frame: 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03924154


Locations
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Sponsors and Collaborators
Altavant Sciences GmbH
Altavant Sciences, Inc.
PPD
Investigators
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Study Director: Ed Parsley, DO Altavant Sciences
More Information
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Additional Information:

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Responsible Party: Altavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03924154    
Other Study ID Numbers: RVT-1201-2001
First Posted: April 23, 2019    Key Record Dates
Last Update Posted: March 9, 2020
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Altavant Sciences GmbH:
Pulmonary arterial hypertension (PAH)
Pulmonary hypertension (PH)
RVT-1201
Rodatristat ethyl
 Tryptophan hydroxylase (TPH)
Serotonin reduction
ELEVATE 1
KAR5417
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
 Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases