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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 : July 13, 2022
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 BID Drug: rodatristat ethyl 600 mg BID 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 BID
rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care

Experimental: Rodatristat Ethyl 600 mg BID
Rodatristat ethyl 600 mg tablet BID + standard of care medication(s) taken for 24 weeks
Drug: rodatristat ethyl 600 mg BID
2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Placebo Comparator: Placebo
Matching placebo tablet + standard of care medication(s) taken for 24 weeks
Drug: Placebo
2 matching placebo tablets on top of standard of care




Primary Outcome Measures :
  1. Percent change from baseline of pulmonary vascular resistance (PVR) as measured by right heart catheterization between active and placebo [ Time Frame: From initiation of treatment to Week 24 ]

Secondary Outcome Measures :
  1. Proportion of patients who improve in WHO World Health Organization (WHO) Functional Class (FC) [ Time Frame: From initiation of treatment to Week 24 ]
  2. Change from baseline in 6MWD [ Time Frame: From initiation of treatment to Week 24 ]
  3. Change from baseline in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels [ Time Frame: From initiation of treatment to Week 24 ]


Information from the National Library of Medicine

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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:

1. Male and female 18 years or older 2. Body Mass Index (BMI) >18kg/m2 to <=40kg/m2 3. Symptomatic PAH belonging to one of the following 2018 WHO Clinical Group 1 subtypes:

a. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with:

  1. Connective tissue disease
  2. Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening
  3. Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows:

    1. stable treatment with HIV medications for at least 8 weeks prior to Screening
    2. no active opportunistic infection during the Screening Period
    3. no hospitalizations due to HIV for at least 4 weeks prior to Screening
  4. WHO FC II or III
  5. Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:

    1. mPAP of >20 mmHg
    2. PVR ≥ 350 dyne•sec/cm5
    3. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 350 and < 500 dyne•sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm5
  6. 6MWD of 100 to 550 meters at Screening
  7. Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the screening RHC (see Protocol Section 6.6.2 for approved PAH medications). Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC.
  8. Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation):

    1. Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and
    2. Total lung capacity (TLC) ≥ 70% of predicted normal or FVC ≥ 70% predicted if TLC is not available; For subjects with CTD associated PAH, if TLC is ≥ 60% of predicted but < 70% of predicted of if FVC ≥ 60% or predicted but < 70% of predicted, high resolution computed tomography [HRCT] obtained within 6 months of screening may be utilized to demonstrate limited interstitial lung disease
  9. If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated ≥ 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of receiving IP. If not participating in an exercise training program for pulmonary rehabilitation, patient must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of receiving IP.

Exclusion Criteria:

  1. Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception
  2. WHO pulmonary hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic PH (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5)
  3. PH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD)
  4. Three or more of the following risk factors for left ventricular disease:

    1. BMI > 30 kg/m2
    2. Diagnosis of essential hypertension that is actively treated
    3. Diabetes mellitus
    4. History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography)
    5. Atrial fibrillation
    6. Left atrial volume index > 41 mL/m2 [or left atrial diameter (LA) > 4 cm if LAVi unavailable]
  5. Known genetic hypertrophic cardiomyopathy
  6. Known cardiac sarcoidosis or amyloidosis
  7. The patient has a history of, or currently has, a constrictive cardiomyopathy.
  8. Known history of any left ventricular ejection fraction (LVEF) < 40% by echocardiogram within 3 years of randomization (Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition [e.g., atrial fibrillation] is allowed).
  9. Hemodynamically significant valvular heart disease as determined by the Investigator, including:

    1. greater than mild aortic and/or mitral stenosis and/or
    2. severe mitral and/or aortic regurgitation (> Grade 3)
  10. Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient's functional limitation and would affect the patient's ability to perform or complete the 6MWT.

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, FCCP +1-203-297-5374 howard.lazarus@altavant.com

Locations
Show Show 60 study locations
Sponsors and Collaborators
Altavant Sciences GmbH
Investigators
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Study Director: Howard M Lazarus, MD, FCCP 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: July 13, 2022
Last Verified: July 2022

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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