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    Summary
    EudraCT Number:2023-001028-40
    Sponsor's Protocol Code Number:RIV-PN-201
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2024-01-15
    Trial results View 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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2023-001028-40
    A.3Full title of the trial
    Intravenous Remodulin (Treprostinil) as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn:
    A Randomized, Placebo-Controlled, Safety and Efficacy Study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A comparative study of intravenously administered treprostinil in neonates
    with Persistent Pulmonary Hypertension of neonates (PPHN) treated in Paediatric Intensive Care Unit.
    A.4.1Sponsor's protocol code numberRIV-PN-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02261883
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/206/2023
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUnited Therapeutics Corp
    B.1.3.4CountryUnited States
    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 supportUnited Therapeutics Corp
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUnited Therapeutics Corp
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street Address55 TW Alexander Drive Research Triangle Park, NC,
    B.5.3.2Town/ cityResearch Triangle Park, NC
    B.5.3.3Post code27709
    B.5.3.4CountryUnited States
    B.5.4Telephone number+19014258167
    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 Yes
    D.2.1.1.1Trade name Remodulin
    D.2.1.1.2Name of the Marketing Authorisation holderFerrer Internacional SA
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Persistant Pulmonary Hypertension of the Newborn (PPHN)
    E.1.1.1Medical condition in easily understood language
    Persistant Pulmonary Hypertension of the Newborn (PPHN)
    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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To explore the safety and treatment effect of intravenous (IV)
    Remodulin as add on therapy in neonates with PPHN compared to
    placebo. Efficacy will be assessed by a composite endpoint of clinical
    worsening through Day 14 as defined by one of the following:
    - Death
    - Initiation of extracorporeal mechanical oxygenation (ECMO) per
    institutional policies
    - Need for additional treatment (initiation of an additional targeted
    pulmonary vasodilator therapy [e.g., phosphodiesterase-5 inhibitor
    [PDE-5i], endothelin receptor antagonist [ERA], prostanoid,
    L-citrulline])
    E.2.2Secondary objectives of the trial
    To assess the effect of IV Remodulin as add on therapy in neonates
    with
    PPHN compared to placebo in the following:
    - Change in Oxygenation Index (OI) from Baseline to Hours 12, 24, 72,
    Days 7 and 14 and/or prior to study drug discontinuation/weaning
    - Change in PaO2 /FiO2 (P/F ratio) from Baseline to Hours 12, 24, 72
    - Change in pre- and post-ductal oxygen saturation (SpO2) from
    Baseline to Hours 6, 12, 24 and 72
    - Time to discontinuation of inhaled nitric oxide (iNO)
    - Time on mechanical ventilation
    - Time to initiation of ECMO
    - Time to clinical worsening
    - Change in N-terminal pro-Brain Naturetic Peptide (NT-proBNP)
    - Safety (adverse events (AEs), clinical laboratories, and physical exam
    findings)
    To evaluate treprostinil pharmacokinetics in neonates with PPHN
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Parent(s) or legal guardian provides consent for the subject to
    participate, as per institutional
    policy.
    2. Weight at least 2 kg at Screening.
    3. Gestational age of at least 34 weeks and is ≤14 days old at
    Screening.
    4. Diagnosis of PPHN, which is either idiopathic in nature or associated
    with the following:
    MAS, pneumonia, RDS, sepsis, birth hypoxia, perinatal encephalopathy
    or unilateral CDH.
    5. Currently requiring ventilator support.
    6. Two consecutive OIs of 15 or greater separated by at least 30
    minutes, after receiving iNO for at least 3 hours.
    7. Echocardiographic evidence of PH (e.g., ductal shunting, significant
    TR) with elevated RV pressures).
    8. Have venous access (central line or peripherally inserted central
    venous catheter [PICC, PCVC]) for the administration of study drug. In
    the event central venous access cannot be established or in the opinion
    of the Investigator the patient is too unstable to attempt to
    establish a central venous access line for IV administration of study
    drug, subjects who are candidates for administration of study drug as a
    continuous SC infusion may be enrolled.
    E.4Principal exclusion criteria
    1. Previous or concurrent use of a PDE-5i, ERA or prostanoid. Previous
    receipt of prostaglandin E1 for ductal patency is allowed.
    2. Significant congenital heart disease (CHD) as detected by ECHO
    (excluding presence of minor defects such as small secundum ASD,
    minor valvular abnormalities, or expected transitional findings such as
    a PFO, or PDA. Subjects with small muscular, restrictive VSD
    may be enrolled).
    3. Clinically significant, untreated active pneumothorax at Screening.
    4. Evidence of clinically significant bleeding (e.g., hemodynamic
    instability or requiring transfusion) at Screening. Note: history of a
    transfusion is not necessarily an exclusion criterion.
    5. Necrotizing entercolitis; defined as Bells stage II or greater at
    Screening.
    6. Uncontrolled hypotension; defined as mean systemic pressures less
    than or equal to 35mmHg at Screening.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is clinical worsening (need for additional
    treatment [initiation of another targeted pulmonary vasodilator
    therapy], initiation of ECMO or death) between Baseline and Day
    14 or time of discharge from the hospital, whichever comes first. It will
    be analyzed as a binary endpoint using the percentage of subjects who
    meet the definition of clinical worsening within each treatment group.
    Subjects who meet the definition of clinical worsening after Day 14 will
    not be counted towards the primary endpoint. Chi-square test will be
    used to test for the treatment difference.
    E.5.1.1Timepoint(s) of evaluation of this end point
    14 days
    E.5.2Secondary end point(s)
    Secondary endpoints (change in OI, P/F ratio, and pre- and post-ductal
    SpO2, time on mechanical ventilation, and change in NT-proBNP) will
    XML File Identifier: OiIQgzcTqJ/cHyJpAAmB7Ut4Uw4=
    Page 8/15 31/10/2023
    be summarized and tested using group t-test. Kaplan-Meier estimate
    will be provided for time to event variables (time to discontinuation of
    iNO, time to initiation of ECMO, and time to clinical worsening) and
    log-rank test will be used to test the treatment differences.
    Plasma samples will be analyzed for treprostinil using a validated
    bioanalytical plasma assay. Individual and mean treprostinil plasma
    concentration data, and treprostinil pharmacokinetic parameters,
    determined as able, will be summarized using descriptive statistics.
    E.5.2.1Timepoint(s) of evaluation of this end point
    12, 24, 72 hours and 7 and 14 days
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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 No
    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 trial2
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA Yes
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    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
    17 May 2023
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 70
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F.1.1.2.1Number of subjects for this age range: 70
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.3.1Number of subjects for this age range: 70
    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) No
    F.1.3Elderly (>=65 years) No
    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 No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    The subject's parent(s) or legal guardian(s) must sign and date an
    IRB/EC-approved informed consent/parental permission form prior to
    the conduct of any study-related activities.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 70
    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)
    None
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Children's Hospital of Los Angeles
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation Stanford Children's Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 3
    G.4.1Name of Organisation ALL Children's Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 4
    G.4.1Name of Organisation Ann and Robert H. Lurie Children's Hospital of Chicago
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 5
    G.4.1Name of Organisation Jonhs Hopkins Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 6
    G.4.1Name of Organisation Universtity of Mississippi Medical Center-Basto Children's Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 7
    G.4.1Name of Organisation Children's Mercy Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 8
    G.4.1Name of Organisation Columbia University Medical Center
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 9
    G.4.1Name of Organisation Nationwide Children's Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 10
    G.4.1Name of Organisation Cook Children's Medical Center
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 11
    G.4.1Name of Organisation Univestity of Virginia Health Systems (UVA)
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 12
    G.4.1Name of Organisation Seattle Children's Hospital
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 13
    G.4.1Name of Organisation Children's Hospital of Wisconsin
    G.4.3.4Network Country United States
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: United States
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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