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Trial record 2 of 4 for:    ralinepag

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients

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ClinicalTrials.gov Identifier: NCT03626688
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Brief Summary:
Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.

Condition or disease Intervention/treatment Phase
PAH Pulmonary Hypertension Pulmonary Arterial Hypertension Hypertension Connective Tissue Diseases Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Hypertension, Pulmonary Lung Diseases Respiratory Tract Disease Drug: Ralinepag Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH
Actual Study Start Date : August 30, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Ralinepag
Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose (maximum dose of 1450 mcg)
Drug: Ralinepag
Active
Other Name: APD811

Placebo Comparator: Placebo
Matching placebo tablets (oral)
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Time (in days) from randomization to the first adjudicated protocol-defined clinical failure event [ Time Frame: From randomization until last visit ]
    Clinical failure events are defined as death, hospital admission for worsening PAH (further defined in clinical study protocol), disease progression (further defined in clinical study protocol), or unsatisfactory long-term clinical response (further defined in clinical study protocol).


Secondary Outcome Measures :
  1. Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: Baseline to Week 28 ]
    NT-proBNP was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

  2. Change from Baseline in 6-minute walk distance (6MWD) [ Time Frame: Baseline to Week 28 ]
    6MWD was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

  3. Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class [ Time Frame: Baseline to Week 28 ]
    The severity of PAH was graded according to the functional status of the subject and assessed at every visit.

  4. Time to all-cause hospitalization [ Time Frame: From randomization until last visit ]
    All hospitalizations during the study period were collected.

  5. Time to all-cause mortality [ Time Frame: From randomization until last visit ]
    All deaths during the study period were collected.

  6. Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT [ Time Frame: Baseline to Week 28 ]
    HRR was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

  7. Proportion of subjects who meet all 3 of the following: NT-proBNP level <300 pg/mL, 6MWD >440 meters, and WHO/NYHA Functional Class II status or better [ Time Frame: Baseline to Week 28 ]
    Data from NT-proBNP, 6MWD, and WHO/NYHA functional class assessment were compiled as a composite endpoint at visits through Week 28.

  8. Change from Baseline in health-related quality of life as measured by SF-36 [ Time Frame: Baseline to Week 28 ]
    Quality of life was assessed using the SF-36 questionnaire at Baseline (prior to starting study drug) and Week 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

  9. Change from Baseline in health-related quality of life as measured by PAH-SYMPACT [ Time Frame: Baseline to Week 28 ]
    Quality of life was assessed using the PAH-SYMPACT questionnaire at Baseline (prior to starting study drug) and Week 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.



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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

Inclusion Criteria:

  • Males or females aged 18-75 years, inclusive.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Diagnosis of symptomatic WHO Group 1
  • Has had a right heart catheterization (RHC) performed at or within 365 days of Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH
  • Has WHO/ NYHA functional class II to IV symptoms.
  • If on PAH-specific background therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or an agent acting on the nitric oxide (NO) pathway, a phosphodiesterase type 5 (PDE5) inhibitor or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatments.

    • Stable is defined as no change in dose or regimen within 90 days of Screening and for the duration of the study.
    • Subjects may be on 1 agent active in the NO pathway, i.e., either a PDE5 inhibitor or an sGC stimulator at stable dose (but not both).
    • If the subject's disease-specific PAH therapy does not include a PDE5 inhibitor, the use of PDE5 inhibitor as needed for erectile dysfunction (ED) is permitted as long as the subject has not taken a dose within 48-hours of any Baseline or study related efficacy assessment. In addition, the subject must not take more than 8 sildenafil tablets, 6 vardenafil, or 4 tadalafil tablets per month for ED.
  • Has a 6MWD of ≥50 meters on two consecutive tests, within 15% of each other, preferably performed on different days during Screening. If both tests are done on the same day, then they must be completed >4 hours apart.
  • Both male and female subjects agree to use a medically acceptable method of contraception throughout the entire study period from informed consent through to the Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process (i.e., actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of IMP. Medically acceptable methods of contraception include the following:

    • oral, implantable, or injectable contraceptives (starting ≥60 days before dosing) and diaphragm with vaginal spermicide, cervical cap with vaginal spermicide, or male condom; male condom and partner using diaphragm with vaginal spermicide or cervical cap with vaginal spermicide;
    • standard intrauterine device (IUD; e.g., Copper T 380A IUD), intrauterine system (IUS; e.g., LNg 20 IUS - progesterone IUD), progesterone implant, or tubal sterilization (≥180 days after surgery);
    • post vasectomy and male condom, partner using diaphragm with spermicide, cervical cap with spermicide, estrogen and progesterone oral contraceptives ("the pill"), estrogen and progesterone transdermal patch, vaginal ring, or progesterone injection. Women who are surgically sterile or postmenopausal for at least 12 months are not considered to be of childbearing potential. If of childbearing potential, female partners of male study participants should agree to utilize medically acceptable methods of contraception for the duration of study participation.

Exclusion Criteria:

  • Body weight <40 kg.
  • Body mass index (BMI) ≥40 kg/m2.
  • Group 2 to 5 pulmonary hypertension.
  • PAH diagnosis ≥5 years at Screening.
  • For subjects with HIV-associated PAH, any of the following:

    • concomitant active opportunistic infections within 180 days of Screening.
    • detectable viral load at Screening.
    • cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Screening.
    • changes in antiretroviral regimen within 90 days of Screening.
  • Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction at Screening:

    • BMI >30 kg/m2.
    • Diabetes mellitus of any type.
    • Systemic hypertension.
    • Significant coronary artery disease, i.e., any of the following:

      • Angina
      • More than 50% stenosis in a coronary artery (by coronary angiography)
      • Previous myocardial infarction
      • Previous or planned coronary artery bypass grafting and/or coronary artery stenting
    • Left atrial volume index (LAVi) >30 mL/m2.
  • Diagnosis of Down syndrome. Subjects with Down syndrome are excluded due to the high potential of undiagnosed or poorly managed obstructive sleep apnea in this population.
  • Malignancy within 5 years of Screening, with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
  • Recent history (i.e., within 1 year prior to Screening) of alcohol or drug abuse.
  • Initiation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.

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): NCT03626688


Contacts
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Contact: Derek Solum, PhD 919-425-8122 dsolum@unither.com
Contact: Miluska Escudero, BS 919-425-5580 mescudero@unither.com

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Sponsors and Collaborators
United Therapeutics
Investigators
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Study Director: Miluska Escudero, BS United Therapeutics

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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT03626688     History of Changes
Other Study ID Numbers: ROR-PH-301
APD811-301 ( Other Identifier: Arena Pharmaceuticals )
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019

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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 United Therapeutics:
Prostacyclin
Connective Tissue Disease-Associated
6 Minute Walk Test
6 Minute Walk Distance
Pulmonary Vascular Resistance
Right Ventricular Function

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