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

Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc0 个研究点目标入组 450 人开始时间: 2021年7月13日最近更新: 2024年2月26日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 450

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Has the following PAH groups, as defined by the Updated Clinical Classification of Pulmonary Hypertension:
•a) Group 1.1 Idiopathic PAH
•b) Group 1.2 Heritable PAH
•c) Group 1.3 Drug and toxin-induced PAH
•d) Group 1.4 PAH associated with:
•? Connective tissue disease
•? HIV infection
•? Simple repaired congenital systemic-to-pulmonary shunt with persistent PH =1 year after surgical repair and with no clinically significant residual shunt
•2. Has a diagnosis of PAH performed as standard of care, per scientific guidelines, and documented by historical RHC at any time prior to Screening; if participant is postsurgical repair of systemic-to pulmonary shunt, diagnostic RHC must have been performed at least 1 year after surgery
•3. Has an eligibility RHC, meeting all the following criteria:
•? mean pulmonary artery pressure (mPAP) =25 mmHg
•? PVR of =3 Wood units
•? PCWP or LVEDP =15 mmHg
•For the Phase 2 Cohort, the eligibility RHC should be performed during Screening and will be centrally reviewed. A participant with RHC performed within 30 days prior to Visit 1/Screening may have the RHC results submitted for central review and, if deemed adequate, the RHC may count as baseline. In each case, the RHC should be performed after at least 90 days of stable PAH-specific therapy
•For the Phase 3 Cohort, an RHC performed within 365 days prior to Visit 1/Screening may count for eligibility assessment. An RHC will be performed during Screening if an RHC performed within 365 days prior to Visit 1/Screening is not available
•4. Has WHO-FC symptoms Class II to IV
•5. Has two 6MWD measurements between 150 and 450 meters, 1 at Screening and 1 at Randomization. The relative difference between the 2 measurements must be =15%. If the relative difference between the two 6MWD measurements is >15%, the Randomization 6MWT may be repeated after at least 4 hours. If the relative difference between the 2 Randomization 6MWD measurements is =15%, the participant can be randomized and the last 6MWD will be considered the baseline value
•6. Has stable concomitant background PAH-specific therapy with any of the following agents:
•? an ERA and/or
•? a PDE5i and/or
•? an oral prostacyclin analogue or oral prostacyclin receptor agonist, an intravenous prostacyclin analogue or a subcutaneous prostacyclin
•7. If on vasodilators other than PAH-specific therapy, has stable concomitant use
•8. If on calcium channel blockers, a participant from Groups 1.1, 1.2, and 1.3 must have a history of being a nonresponder to acute pulmonary vasoreactivity testing
•9. If on anticoagulants, has stable concomitant use for at least 30 days prior to and over the duration of Screening
•10. Is male or female, from 18 years to 75 years of age inclusive, at the time of signing the informed consent
•11. Has a BMI between 18.5 kg/m2 and 40 kg/m2
•12. Is willing to comply with scheduled visits, treatment plan, laboratory tests, and/or other study procedures and study restrictions
•13. Agrees to allowing site contact via phone or email for follow-up purposes
•14. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 14 days after the last dose of study intervention:
•? Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR
•? Must agree to use contraception unless confirmed to be azoospermic as detailed below:
•- Agree to use a male condom plus partner use of an additional contraceptive

排除标准

•1. Has Group 2 to 5 Pulmonary Hypertension in the Updated Clinical Classification of Pulmonary Hypertension
•2. Has Group 1.5 PAH, long-term responders to calcium channel blockers, defined by sustained clinical improvement to WHO-FC I or II and sustained hemodynamic improvement after at least 1 year on CCBs only
•3. Has Group 1.6 PAH, with overt features of venous/capillary (PVOD/PCH) involvement
•4. For participants with Group 1.4 HIV-associated PAH, has any of the following within 90 days prior to and for the duration of Screening:
•? concomitant active opportunistic infections
•? plasma HIV-1 RNA=50 copies/mL or CD4+ T-cell count<200/mm3
•? changes in antiretroviral regimen
•5. Has evidence of more-than-mild obstructive lung disease on PFT at Screening: FEV1/FVC <70%; and FEV1 <60% of predicted value after bronchodilator administration
•6. Has evidence of more-than-mild parenchymal lung disease, based on medical history and chest imaging , and/or restrictive lung disease with Total Lung Capacity <60% of predicted on PFT at Screening
•7. Has evidence of OSA that is untreated. Participants with well-controlled, treated OSA are eligible
•8. Has evidence or history of left heart disease, including any of the following:
•? left ventricular ejection fraction =45%
•? moderate or severe left-sided valvular disease
•? Grade 3 and 4 left ventricular diastolic function on echocardiographic evaluation
•9. Has 3 or more of the following risk factors for heart failure with preserved ejection fraction:
•? BMI >30 kg/m2
•? history of essential systemic hypertension
•? diabetes mellitus of any type
•? history of coronary artery disease
•10. Has oxygen saturation measured by pulse oximetry <90%, despite supplemental oxygen therapy
•11. Had clinically unstable or acutely decompensated right heart failure within 30 days prior to and over the duration of Screening including, but not limited to, hospitalization or emergency room visit for acute decompensated heart failure
•12. Has sitting systolic BP >160 mmHg or <90 mmHg or sitting diastolic BP >100 mmHg
•13. Has significant chronic renal insufficiency, as defined by eGFR <30 mL/min or by ongoing dialytic support
•14. Has evidence of chronic liver disease, portal hypertension,
•cirrhosis, or hepatic laboratory abnormalities
•15. Is included in a cardiopulmonary rehabilitation program initiated within 90 days prior to Screening or is planning to initiate cardiopulmonary rehabilitation during the study
•16. Has acute or chronic impairment(s), limiting the ability to perform 6MWT
•17. Is a current smoker or currently uses electronic cigarettes
•18. Is unable to correctly use the DPI prior to randomization due to, but not limited to, cognitive impairment or physical limitations
•19. Has other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation
•20. Has a history of cancer. Exceptions:1) Adequately treated
•nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or;2) Other malignancies which have been successfully treated, with appropriate follow up, and therefore unlikely to recur for the duration of the study, in the opinion of the investigator
•21. Has a known hypersensitivity to any of the ingredients or excipients of the IMP
•22. At the time of signing the informed consent, is a user of illicit drugs or has had a recent history of drug or alcohol abuse or dependence

研究者

发起方

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

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