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Trial record 1 of 42474 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 : Recruiting
First Posted : April 23, 2019
Last Update Posted : September 18, 2019
Sponsor:
Collaborators:
Altavant Sciences, Inc.
PPD
Information provided by (Responsible Party):
Altavant Sciences GmbH

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 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
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020


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)




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
  • Pulmonary function tests prior to screening that 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) >35
  • Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception

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


Contacts
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Contact: Julie Rurka 919.808.4339 info@altavant.com
Contact: Liz Mascherino info@altavant.com

Locations
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United States, Arizona
Pulmonary Associates, PA Recruiting
Phoenix, Arizona, United States, 85006
Contact: Liyi Fu    602-258-4951    palyf@aol.com   
Principal Investigator: David Baratz, MD         
United States, California
SBPA Research LLC Recruiting
Santa Barbara, California, United States, 93105
Contact: Vinh Truong    805-898-8840    vinht@sblung.com   
Principal Investigator: Jeffrey Sager, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Kelly Hannon    720-848-6552    Kelly.Hannon@CUAnschutz.edu   
Principal Investigator: David Badesch, MD         
United States, District of Columbia
George Washington Medical Faculty Associates - Pulmonary Hypertension Program Recruiting
Washington, District of Columbia, United States, 20037
Contact: Sara Smith    202-741-2581    sarsmith@mfa.gwu.edu   
Principal Investigator: Mardi Gomberg-Maitland, MD         
United States, Florida
San Marcus Research Clinic, Inc. Recruiting
Miami Lakes, Florida, United States, 33014
Contact: Liz Alvarez    305-424-7420    lalvarez@sanmarcusrc.com   
Principal Investigator: Belkis Delgado, MD         
Central Florida Pulmonary Group, P.A. Recruiting
Orlando, Florida, United States, 32803
Contact: Shynessa Ogletree    407-841-1100 ext 121    sogletree@cfpulmonary.com   
Principal Investigator: Syed Mobin, MD         
United States, Kentucky
Kentuckiana Pulmonary Research Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Kimberly Hobbs Robinson    502-587-8000    krobinson@kpadocs.com   
Principal Investigator: John W McConnell, MD         
United States, Louisiana
Louisiana State University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Paula Lauto    504-568-3451    plauto@lsuhsc.edu   
Principal Investigator: Matthew Lammi, MD         
United States, Michigan
Pulmonary Research Institute of Southeast Michigan Recruiting
Farmington Hills, Michigan, United States, 48336
Contact: Emily Moiseeff    248-478-6561    pulmonary.research1@gmail.com   
Principal Investigator: Gary Ferguson, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ellen Newton-Lovato    314-454-8717    elovato@wustl.edu   
Principal Investigator: Murali Chakinala         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Susana Almeida-Peters, BN RN    919-668-2642    susana.almeida-peters@duke.edu   
Principal Investigator: Sudarshan Rajagopal, MD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Olivia Krol    503-494-6994    krolo@ohsu.edu   
Principal Investigator: Akram Khan, MD         
United States, Texas
University of Texas Health Science Center at Houston, McGovern Medical School Not yet recruiting
Houston, Texas, United States, 77030
Contact: Mary Rangel    713-500-6851    mary.rangel@uth.tmc.edu   
Principal Investigator: Namita Sood, MD         
Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T1Y6J4
Contact: Jean Marks    403-943-4759    jean.marks@albertahealthservices.ca   
Principal Investigator: Jason Weatherald, MD         
Sponsors and Collaborators
Altavant Sciences GmbH
Altavant Sciences, Inc.
PPD
Investigators
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Study Director: Laurence Keller, MD Altavant Sciences, Inc.

Additional Information:
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Responsible Party: Altavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03924154     History of Changes
Other Study ID Numbers: RVT-1201-2001
First Posted: April 23, 2019    Key Record Dates
Last Update Posted: September 18, 2019
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