A Phase 2a Study to Evaluate the Safety and Efficacy of MK-5475 in Adults With Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

1 Mar 2023 → ongoing

Decision date (initial)

2023-01-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501201-13-00

WHO UTN

U1111-1279-8512

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Safety, Diagnosis, Efficacy

To evaluate the effect of MK-5475 versus placebo on 6-minute walk distance (6MWD) at Week 24

Secondary objectives 4

1. To evaluate the effect of MK-5475 versus placebo on 6MWD at Week 12
2. To evaluate the effect of MK-5475 versus placebo on N-terminal pro B-type natriuretic peptide (NT-proBNP) levels at Week 12 and Week 24
3. To evaluate the effect of MK-5475 versus placebo on the World Health Organization (WHO) Functional Class at Week 12 and Week 24
4. To evaluate the safety and tolerability of MK-5475

Conditions and MedDRA coding

Pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD).

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has Group 3.1 pulmonary hypertension chronic obstructive pulmonary disease (PH-COPD) as defined by the Clinical Classification of Pulmonary Hypertension
2. Has a right heart catheterization (RHC) at screening or historical RHC within 12 months before screening that meets hemodynamic criteria
3. Has evidence of obstructive lung disease on pulmonary function testing (PFT) performed at screening
4. Has a WHO Functional Class assessment of Class II to IV
5. If on supplemental oxygen, the regimen must be stable
6. Has stable and optimized chronic, baseline COPD-specific therapy
7. If on PDE5 inhibitor, has stable concomitant use
8. If on antihypertensives and/or a diuretic regimen has stable concomitant use
9. If on anticoagulants has stable concomitant use
10. Is of any sex/gender from 40 to 85 years of age inclusive
11. Female is not pregnant or breastfeeding, and is not of childbearing potential or uses acceptable contraceptive method or abstains from sexual intercourse, or has a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention, or whose history and sexual activity has been reviewed by the investigator

Exclusion criteria 17

1. Has history of Group 1 pulmonary arterial hypertension (PAH), Groups 2, 4 or 5 pulmonary hypertension (PH)
2. Has history of non-COPD related Group 3 PH
3. Has evidence of untreated more than mild obstructive sleep apnea
4. Has significant left heart disease
5. Expects to receive a lung and/or heart transplant from screening through the end of the 24 week Base Period
6. Has evidence of a resting oxygen saturation (SpO2) < 88%
7. Has experienced a moderate or severe COPD exacerbation within 2 months before randomization
8. Has experienced right heart failure within 2 months before randomization
9. Has uncontrolled tachyarrhythmia
10. Has acute coronary syndrome, undergone coronary artery bypass graft, or percutaneous coronary intervention within 2 months before randomization
11. Has evidence of significant chronic renal insufficiency
12. Has evidence of chronic liver disease, portal hypertension, cirrhosis, or hepatic abnormalities
13. Initiated a pulmonary rehabilitation program within 2 months before randomization
14. Has impairments that limit the ability to perform 6MWT
15. Has history of cancer
16. Is a user of illicit drugs or has a recent history of drug/alcohol abuse or dependence
17. Has used PAH-specific therapies within 2 months of randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline in 6-minute walk distance (6MWD) at Week 24

Secondary endpoints 7

1. Mean change from baseline in 6MWD at Week 12
2. Mean change from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) at Week 12
3. Mean change from baseline in NT-proBNP at Week 24
4. Percentage of participants whose World Health Organization (WHO) Functional Class does not worsen relative to baseline at Week 12
5. Percentage of participants whose WHO Functional Class does not worsen relative to baseline at Week 24
6. Percentage of participants with one or more adverse events (AEs)
7. Percentage of participants who discontinued study treatment due to an AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mackenzie Ford

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mackenzie Ford

Third parties 6

Locations

6 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 91 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications