Phase 2/3 Study of MK-5475 in Adults with Pulmonary Arterial Hypertension

  • Research type

    Research Study

  • Full title

    A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults with Pulmonary Arterial Hypertension

  • IRAS ID

    1003596

  • Contact name

    Dragos Vladimir Budinschi Agachi

  • Contact email

    dragos.budinschi@merck.com

  • Sponsor organisation

    Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc

  • Eudract number

    2020-001108-40

  • Clinicaltrials.gov Identifier

    NCT04732221

  • Research summary

    This is a multicentre, randomised, placebo-controlled, parallel-group, double-blind Phase 2/3 study to evaluate the efficacy, safety, and tolerability of inhaled MK-5475 in participants with Pulmonary Arterial Hypertension (PAH) sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (“MSD”), of Kenilworth, New Jersey, USA.

    PAH defines a group of rare, progressive conditions characterised by increased vascular resistance in the pulmonary arterial circulation. Despite substantial progress in PAH management, increased awareness, and multiple PAH-specific therapies, the long-term prognosis for patients remains poor and the disease can progress to right-sided heart failure and death.

    This study will be carried out in 2 parts: A Phase 2 dose selection cohort and a Phase 3 confirmatory cohort (12-week Base Period and Extension Period).

    Phase 2:
    Participants will take part in the Phase 2 dose selection cohort for approximately 18 weeks - Screening period of up to 4 weeks, a 12-week double-blind treatment period, and a 2-week Follow-up.
    Approximately 164 male and female participants, aged 18 to 75 years with PAH will be enrolled and randomised in a 1:1:1:1 ratio, to one of the four treatment groups: MK-5475 380 micrograms (µg), MK-5475 100 µg, MK-5475 32 µg or placebo which will be orally inhaled once daily for 12 weeks.
    Of the 3 MK-5475 doses studied in Phase 2, the dose with the best efficacy and safety profile in this cohort will be evaluated in the subsequent Phase 3 confirmatory cohort.

    Phase 3:
    The Phase 3 cohort consists of a Screening period of up to 4 weeks, Base period consisting of a 12-week double-blind treatment period, Extension period where participants will continue the double-blind treatment period up to 5 years, and a 2-week Follow-up.
    Approximately 286 male and female participants, aged 18 to 75 years with PAH will be randomised in a 1:1 ratio, to MK-5475 (Dose selected at the end of the Phase 2 Cohort) or placebo.

  • REC name

    North West - Greater Manchester Central Research Ethics Committee

  • REC reference

    21/NW/0055

  • Date of REC Opinion

    19 Apr 2021

  • REC opinion

    Further Information Favourable Opinion