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A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2)

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ClinicalTrials.gov Identifier: NCT04712669
Recruitment Status : Recruiting
First Posted : January 15, 2021
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Altavant Sciences GmbH

Brief Summary:
The purpose of this study is to assess the safety and efficacy of Rodatristat Ethyl in pulmonary arterial hypertension (PAH) patients.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Rodatristat Ethyl 300 mg tablet Drug: Placebo Phase 2

Detailed Description:

Rodatristat Ethyl is a peripherally restricted TPH inhibitor being studied as a potential treatment for PAH. This dose-ranging, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effect of Rodatristat Ethyl from baseline on pulmonary vascular resistance as measured at right heart catheterization.

Patients will be enrolled into a main study with an option to enroll into an open label extension.

The study is expected to enroll patients in the USA, Canada and Europe.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Following screening assessments, Patients will be enrolled into 1 of 3 treatment arms in a 1:1:1 randomization.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension
Actual Study Start Date : March 15, 2021
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Rodatristat Ethyl 300 mg BID
Rodatristat ethyl 300 mg tablet BID + standard of care medication(s) taken for 24 weeks
Drug: Rodatristat Ethyl 300 mg tablet
Rodatristat ethyl is a tryptophan hydroxylase (TPH) inhibitor designed to block peripheral serotonin production.

Drug: Placebo
Inactive pill manufactured to mimic rodatristat ethyl

Experimental: Rodatristat Ethyl 600 mg BID
Rodatristat ethyl 600 mg tablet BID + standard of care medication(s) taken for 24 weeks
Drug: Rodatristat Ethyl 300 mg tablet
Rodatristat ethyl is a tryptophan hydroxylase (TPH) inhibitor designed to block peripheral serotonin production.

Placebo Comparator: Placebo
Matching placebo tablet + standard of care medication(s) taken for 24 weeks
Drug: Placebo
Inactive pill manufactured to mimic rodatristat ethyl




Primary Outcome Measures :
  1. Change from baseline of pulmonary vascular resistance as measured by right heart catheterization [ Time Frame: From initiation to Week 24 ]

Secondary Outcome Measures :
  1. Change from baseline of cardiac index (CI) [ Time Frame: From initiation to Week 24 ]
  2. Change from baseline of mean pulmonary artery pressure (mPAP) [ Time Frame: From initiation to Week 24 ]
  3. Change from baseline of mean mixed venous oxygen saturation (SvO2) [ Time Frame: From initiation to Week 24 ]
  4. Change from baseline of pulmonary artery compliance (PAC) [ Time Frame: From initiation to Week 24 ]
  5. Time to the first occurrence of a clinical worsening event (TTCW) [ Time Frame: From initiation to Week 24 ]
    Time to Clinical Worsening (TTCW) defined as the first occurrence of: 1. Death from any cause, 2. Hospitalization for worsening PAH (any hospitalization for worsening PAH, lung or heart and lung transplantation, atrial septostomy, or initiation of parenteral prostanoid therapy), 3. Disease progression defined as a decrease of more than 15% from Baseline in the 6-minute walk distance (6MWD) combined with World Health Organization (WHO) Functional Class (FC) III or IV symptoms at 2 consecutive visits separated by at least 14 days (adjudicated)

  6. Change in baseline in WHO FC World Health Organization (WHO) Functional Class (FC) [ Time Frame: From initiation to Week 24 ]
  7. Change from baseline in 6MWD [ Time Frame: From initiation to Week 24 ]
  8. Change from baseline in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels [ Time Frame: From initiation to Week 24 ]
  9. Change from baseline in of right atrial size by echocardiogram [ Time Frame: From initiation to Week 24 ]
  10. Change from baseline in the tricuspid annular systolic velocity by echocardiogram [ Time Frame: From initiation to Week 24 ]
  11. Change from baseline in the tricuspid annular plane systolic excursion (TAPSE) by echocardiogram [ Time Frame: From initiation to Week 24 ]
  12. Change from baseline in the RV fractional area change by echocardiogram [ Time Frame: From initiation to Week 24 ]
  13. Change in baseline in the Pulmonary Arterial Hypertension Symptoms and Impact Questionnaire (PAH SYMPACT) Score [ Time Frame: From initiation to Week 24 ]
  14. Change in baseline in the Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 score [ Time Frame: From initiation to Week 24 ]
  15. Change from baseline in plasma and urine 5-hydroxyindoleacetic acid (5-HIAA) [ Time Frame: From initiation to Week 24 ]

Other Outcome Measures:
  1. Time to Clinical Improvement (TTCI) [ Time Frame: From initiation to Week 24 ]
    A > 10% increase in 6MWD or 30 meters AND an improvement to or maintenance of WHO FC II symptomatology, in the absence of a deterioration in clinical condition or death during the 24 weeks of the Main Study

  2. Change from baseline on the following actigraphy endpoints: [ Time Frame: From initiation to Week 24 ]
    1. Light to vigorous activity/day, 2. Moderate to vigorous activity/day, 3.Total movement/day, 4.Best 6-minute walk effort



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female 18 years or older
  • Body Mass Index (BMI) 18kg/m2 to 38kg/m2
  • Symptomatic PAH belonging to WHO Group 1 on a stable treatment regimen with one or more approved PAH treatments
  • PAH defined as mean pulmonary artery pressure ≥ 20 mmHg during right heart catheterization performed at rest
  • FEV1 ≥ 60 % of predicted normal, FEV1:FVC ratio ≥ 0.70 or TLC ≥ 70% of predicted normal
  • WHO FC II or III

Exclusion Criteria:

  • Pregnant women
  • WHO Pulmonary Hypertension (PH) Group 2 - 5
  • PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD))
  • Three or more risk factors for left ventricular disease; BMI ≥ 30 kg/m^2, diagnosis of essential hypertension that is actively treated, diabetes mellitus, history of significant coronary artery disease, atrial fibrillation, and/or left atrial volume index > 41 mL/m^2
  • Known genetic hypertrophic cardiomyopathy, or cardiac sarcoidosis or amyloidosis
  • The patient has a history of, or currently has, a constrictive cardiomyopathy
  • Known history of any LVEF < 40% by echocardiogram within 3 years of randomization
  • Hemodynamically significant valvular heart disease
  • Patient severely disabled and unable to complete the study
  • End stage renal disease or severe liver disease
  • Known congenital long QT syndrome (LQTS) or known family history of LQTS
  • Depression that is currently rated as severe or recent suicidal behavior or active suicidal ideation with intent to act
  • Uncontrolled arterial hypertension or hypotension
  • Patients currently taking one or more drugs known to prolong the QT interval and which are clearly associated with a known risk of Torsades de Pointe
  • QTcF interval > 450 ms for males or > 470 ms for females
  • Any ECG or clinical laboratory abnormality which precludes safe participation in the study in the opinion of the Investigator

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): NCT04712669


Contacts
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Contact: Watiri Kamau-Kelley +1-408-300-3316 watiri@altavant.com
Contact: Howard Lazarus, MD +1-203-297-5374 howard.lazarus@altavant.com

Locations
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United States, Arizona
Arizona Pulmonary Specialists Recruiting
Phoenix, Arizona, United States, 85012
Contact: Jeremy Feldman, MD       jpfeldman1@yahoo.com   
United States, California
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95816
Contact: Namita Sood, MD       nsood@ucdavis.edu   
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: David Badesch, MD       david.badesch@ucdenver.edu   
United States, District of Columbia
George Washington University Medical Center Recruiting
Washington, District of Columbia, United States, 20037
Contact: Mardi Gomberg-Maitland, MD       mgomberg@mfa.gwu.edu   
United States, Kansas
The University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Leslie Spikes, MD       lspikes@kumc.edu   
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Nicholas Hill, MD       nhill@tuftsmedicalcenter.org   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Murali Chakinala, MD       chakinalam@wustl.edu   
United States, Rhode Island
Brown University - Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Corey Ventetuolo, MD       corey_ventetuolo@brown.edu   
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Kelly Chin, MD       kelly.chin@utsouthwestern.edu   
Sponsors and Collaborators
Altavant Sciences GmbH
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Responsible Party: Altavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT04712669    
Other Study ID Numbers: RVT-1201-2002 / ELEVATE 2
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021

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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:
PAH
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases