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    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-004971-42
    Sponsor's Protocol Code Number:RVT-1201-2002
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-04-28
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2020-004971-42
    A.3Full title of the trial
    A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients with Pulmonary Arterial Hypertension
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2)
    A.3.2Name or abbreviated title of the trial where available
    ELEVATE 2
    A.4.1Sponsor's protocol code numberRVT-1201-2002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04712669
    A.5.4Other Identifiers
    Name:INDNumber:126945
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAltavant Sciences GmbH
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAltavant Sciences GmbH
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAltavant Sciences GmbH
    B.5.2Functional name of contact pointInformation Desk
    B.5.3 Address:
    B.5.3.1Street AddressViaduktstrasse 8
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4051
    B.5.3.4CountrySwitzerland
    B.5.6E-mailclinicaltrials@altavant.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1861
    D.3 Description of the IMP
    D.3.1Product nameRodatristat ethyl
    D.3.2Product code RVT-1201
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRodatristat ethyl
    D.3.9.1CAS number 1673571-51-1
    D.3.9.2Current sponsor codeRVT-1201
    D.3.9.3Other descriptive nameRodatristat ethyl
    D.3.9.4EV Substance CodeSUB198073
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary Arterial Hypertension (PAH)
    E.1.1.1Medical condition in easily understood language
    Pulmonary Arterial Hypertension (PAH) is a serious and rare disease of increased blood pressure within the arteries of the lungs.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10037400
    E.1.2Term Pulmonary hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of rodatristat ethyl on the percent change from baseline of pulmonary vascular resistance (PVR), as measured by right heart catheterization (RHC) in patients with PAH.
    E.2.2Secondary objectives of the trial
    • To evaluate the effect of rodatristat ethyl from baseline to Week 24 on:
    o Cardiopulmonary Hemodynamics
    o Time to Clinical Worsening (TTCW)
    o Death from any cause
    o WHO FC
    o 6MWD
    o N-terminal pro-Brain Natriuretic Peptide (NT-proBNP)
    o Echocardiographic measures of right atrial size & RV function (tricuspid annular plane systolic excursion [TAPSE], tricuspid annular systolic velocity, and RV fractional area change)
    o Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT)
    o Register to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 score
    • To assess safety & tolerability of rodatristat ethyl in patients with PAH
    • To assess the PK of rodatristat ethyl
    • To assess the effect of rodatristat ethyl on plasma and urinary 5-HIAA
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients are eligible to be included in the study only if all the following criteria are met:
    1. Male and female patients must be at least 18 years of age at the time of signing the informed consent.
    a. Male patients and female partners of childbearing potential must agree to use contraception as detailed in a Section 5.4.1 to the protocol starting 4 weeks prior to the first dose of IP, during the treatment period, and for at least 100 days after the last dose of IP. Male patients must refrain from donating sperm during this period.
    b. Female patients of childbearing potential must agree to use contraception as detailed in Section 5.4.1 starting at Screening, during the treatment period, and for at least 4 weeks after the last dose of IP.
    2. Body mass index (BMI) ≥ 18 kg/m2 and ≤ 38 kg/m2
    3. Patients with symptomatic PAH belonging to one of the following 2018 Clinical Group 1 sub types:
    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:
    a. stable treatment with HIV medications for at least 8 weeks prior to Screening
    b. no active opportunistic infection during the Screening Period
    c. 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:
    a. mPAP of ≥ 20 mmHg
    b. PVR ≥ 400 dyne•sec/cm5
    c. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 400 and < 500 dyne•sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm5
    d. 6MWD of 100 to 550 meters at Screening
    6. 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. 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.
    7. 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):
    a. Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and
    b. FEV1:FVC ratio ≥ 0.70, and
    c. Total lung capacity (TLC) ≥ 70% of predicted normal (high resolution computed tomography [HRCT] required for TLC ≥ 60% and < 70%)
    8. 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.
    9. Willing and able to give written informed consent and to comply with the requirements of the study for its duration
    E.4Principal exclusion criteria
    Patients are excluded from the study if any of the following criteria are met:
    1. Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception as defined in Section 5.4.1
    Medical Conditions
    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. PAH 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:
    a. BMI > 30 kg/m2
    b. Diagnosis of essential hypertension that is actively treated
    c. Diabetes mellitus
    d. 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)
    e. Atrial fibrillation
    f. Left atrial volume index > 41 mL/m2
    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:
    a. greater than mild aortic and/or mitral stenosis and/or
    b. 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.
    11. Planned major surgery within the next 3 months, including lung transplantation, major abdominal or major intestinal surgery
    12. End stage renal disease defined as receiving peritoneal dialysis, hemodialysis, or status after renal transplantation, or severe liver disease defined as Child Pugh Class C, with or without cirrhosis
    13. Known congenital LQTS or known family history of LQTS
    14. Depression that is currently rated as severe (defined as a score of ≥ 16 on the QIDS C and/or [HADS] Depression and/or Anxiety score ≥ 15), recent suicidal behavior (either preparatory acts/behavior, aborted attempt, interrupted attempt, or actual attempt in the past 3 months per the Screening C SSRS), or active suicidal ideation with intent to act (defined as C SSRS category score of 4 or 5 in the past month)
    15. Uncontrolled arterial hypertension (SBP > 180 mmHg and/or Diastolic Blood Pressure [DBP] > 110 mmHg), or hypotension (SBP < 90 mmHg and/or DBP < 50 mmHg)
    16. Clinically significant electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, or hypocalcemia) in the judgement of the Investigator
    17. Current or prior history within the last 5 years of neoplasm (except for treated basal cell or squamous small cell carcinoma of the skin with no evidence of recurrence)
    18. Any concurrent clinically significant medical condition/disorder which in the Investigator’s opinion would interfere with the patient’s ability to comply with or complete the study or could affect the interpretation of the efficacy and safety variables.
    Prior/Concomitant Therapy
    19. Use of any of the following medications or supplements within 30 days prior to Screening:
    •monoamine oxidase inhibitors (MAOIs)
    •5 hydroxytryptophan (5-HTP) or L tryptophan
    •telotristat ethyl
    20. 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 (see Appendix 1)
    Diagnostic Assessments
    21. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at Screening
    22. 12 Lead ECG results at Screening demonstrating QTcF interval > 450 ms for males or > 470 ms for females
    23. Elevated ALT, AST, or TBL > 2X ULN
    24. Any ECG or clinical laboratory abnormality which precludes safe participation in the study in the opinion of the Investigator
    Lifestyle
    25. History of active substance abuse disorder (including alcohol) within the past 2 years which, in the option of the Investigator, would limit the ability of the patient to provide adequate informed consent or to comply with study requirements
    26. Use of any investigational drug within 30 days or 5 half lives (whichever is longer) prior to Screening, or 90 days if an investigational drug for PAH, unless local health authority guidelines mandate a longer period
    E.5 End points
    E.5.1Primary end point(s)
    Percent change from baseline to 24 weeks of pulmonary vascular resistance (PVR) between an active arm and the placebo arm.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    • Change from baseline in cardiac index, mPAP, mRAP, SvO2 at rest and PAC
    • Change from baseline in TTCW
    • Death from any cause
    • Change from baseline in WHO FC
    • Change from baseline in 6MWD
    • Change from baseline in NT proBNP
    • Change from baseline in right atrial size & RV function (TAPSE, tricuspid annular systolic velocity, & RV fractional area change)
    • Change from baseline in PAH SYMPACT
    • Change from baseline in REVEAL Lite 2.0 Score
    • Safety parameters including AEs, vital signs, laboratory values, and electrocardiogram (ECG) assessments
    • Population PK parameters of rodatristat ethyl and active metabolite rodatristat
    • Change from baseline in 5 hydroxyindoleacetic acid (5 HIAA; plasma and spot urine concentration)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Bosnia and Herzegovina
    Bulgaria
    Canada
    Czechia
    France
    Germany
    Italy
    Latvia
    Poland
    Russian Federation
    Serbia
    Spain
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days22
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 39
    F.4.2.2In the whole clinical trial 90
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients in the Main Study that do not discontinue prematurely and complete up to and including the Week 24 Visit, have the option to rollover into the Open Label Extension (OLE).
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-05-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-12
    P. End of Trial
    P.End of Trial StatusOngoing
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