Register a trial

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04732221




Registration number
NCT04732221
Ethics application status
Date submitted
27/01/2021
Date registered
1/02/2021

Titles & IDs
Public title
A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)
Scientific 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
Secondary ID [1] 0 0
MK-5475-007
Secondary ID [2] 0 0
5475-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Hypertension, Pulmonary 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MK-5475
Treatment: Drugs - Placebo to MK-5475

Experimental: Phase 2 Cohort MK-5475 380 µg - Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.

Experimental: Phase 2 Cohort MK-5475 100 µg - Participants receive MK-5475 100 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.

Experimental: Phase 2 Cohort MK-5475 32 µg - Participants receive MK-5475 32 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.

Placebo comparator: Phase 2 Cohort Placebo - Participants receive placebo via oral inhalation once daily for 12 week base period, and one of the MK-5475 doses (380, 100, or 32 µg) for the optional 24 month extension period.

Experimental: Phase 3 Cohort MK-5475 - Participants receive one of 3 MK-5475 doses (380, 100 or 32 µg) to be selected at end of the Phase 2 Cohort, administered via oral inhalation once daily for 12-week base period and up to 60 months in the extension period

Placebo comparator: Phase 3 Cohort Placebo - Participants receive placebo via oral inhalation once daily for 12 week base period and up to 60 months in the extension period.


Treatment: Drugs: MK-5475
MK-5475 (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation

Treatment: Drugs: Placebo to MK-5475
Placebo administered as dry powder inhalation
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 2 Cohort: Change from Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks
Timepoint [1] 0 0
At baseline and 12 weeks
Primary outcome [2] 0 0
Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
Timepoint [2] 0 0
At baseline and 12 weeks
Secondary outcome [1] 0 0
Phase 2 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
Timepoint [1] 0 0
At baseline and 12 weeks
Secondary outcome [2] 0 0
Phase 2 Cohort: Change from Baseline in Mean Right Arterial Pressure (mRAP) at 12 Weeks
Timepoint [2] 0 0
At baseline and 12 weeks
Secondary outcome [3] 0 0
Phase 2 Cohort: Change from Baseline in Cardiac Index (CI) at 12 weeks
Timepoint [3] 0 0
At baseline and 12 weeks
Secondary outcome [4] 0 0
Phase 2 Cohort: Change from Baseline in Stroke Volume Index (SVI) at 12 weeks
Timepoint [4] 0 0
At baseline and 12 weeks
Secondary outcome [5] 0 0
Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
Timepoint [5] 0 0
At baseline and 24 weeks
Secondary outcome [6] 0 0
Phase 3 Cohort: Change from Baseline in World Health Organization Functional Class (WHO-FC) at 12 Weeks
Timepoint [6] 0 0
At baseline and 12 weeks
Secondary outcome [7] 0 0
Phase 2 Cohort: Number of Participants Who Experience an Adverse Event
Timepoint [7] 0 0
Up to approximately 2.25 years
Secondary outcome [8] 0 0
Phase 2 Cohort: Number of Participants Who Discontinue Study Drug Due to an Adverse Event
Timepoint [8] 0 0
Up to approximately 2.25 years
Secondary outcome [9] 0 0
Phase 3 Cohort: Number of Participants who Experience an Adverse Event
Timepoint [9] 0 0
Up to approximately 5.5 years
Secondary outcome [10] 0 0
Phase 3 Cohort: Number of Participants who Discontinue Study Drug Due to an Adverse Event
Timepoint [10] 0 0
Up to approximately 5.5 years

Eligibility
Key inclusion criteria
* Pulmonary arterial hypertension (PAH) in one of the following groups:

* Idiopathic PAH
* Heritable PAH
* Drug and toxin-induced PAH
* PAH associated with connective tissue disease, HIV infection, or congenital heart disease.
* Diagnosis of PAH documented by right heart catheterization (RHC).
* Eligibility RHC meeting all of the following criteria:

* Mean pulmonary artery pressure (mPAP) =25 mmHg
* Pulmonary vascular resistance (PVR) of =3 Wood units
* Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) =15 mmHg.
* World Health Organization functional class (WHO-FC) symptoms between Class II and IV.
* Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening and one at randomization.
* Stable concomitant background PAH-specific therapy.
* Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² .
* Agree to be abstinent from heterosexual intercourse or use contraception during the intervention period and for at least 14 days after the last dose of study intervention.
* Female participants may not be pregnant or breastfeeding.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Group 2 to 5 pulmonary hypertension.
* PAH in one of the following groups:

* Long term responders to calcium channel blockers
* Overt features of venous/capillary involvement
* Evidence of more-than-mild obstructive lung disease.
* Evidence of more-than-mild parenchymal lung disease.
* Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated.
* Evidence or history of left heart disease, including any of the following:

* Left ventricular ejection fraction (LVEF) =45%
* Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation)
* Significant left ventricular diastolic dysfunction on echocardiographic evaluation
* Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease.
* Oxygen saturation measured by pulse oximetry (SpO2) <90%, despite supplemental oxygen therapy.
* Chronic renal insufficiency (eGFR <30 mL/min)
* Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities.
* Current smoker or currently uses electronic cigarettes (vapes).
* History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/07/2024
Sample size
Target
Accrual to date
Final
168
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Nepean Hospital ( Site 0184) - Kingswood
Recruitment hospital [2] 0 0
Macquarie University ( Site 0180) - Macquarie University
Recruitment hospital [3] 0 0
John Hunter Hospital ( Site 0185) - Newcastle
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
2109 - Macquarie University
Recruitment postcode(s) [3] 0 0
2305 - Newcastle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Mexico
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
West Virginia
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Caba
Country [21] 0 0
Argentina
State/province [21] 0 0
Santa Fe
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Belgium
State/province [23] 0 0
Bruxelles-Capitale, Region De
Country [24] 0 0
Belgium
State/province [24] 0 0
Vlaams-Brabant
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Colombia
State/province [28] 0 0
Antioquia
Country [29] 0 0
Colombia
State/province [29] 0 0
Distrito Capital De Bogota
Country [30] 0 0
Colombia
State/province [30] 0 0
Santander
Country [31] 0 0
France
State/province [31] 0 0
Finistere
Country [32] 0 0
France
State/province [32] 0 0
Haute-Garonne
Country [33] 0 0
France
State/province [33] 0 0
Nord-Pas-de-Calais
Country [34] 0 0
France
State/province [34] 0 0
Seine-Maritime
Country [35] 0 0
France
State/province [35] 0 0
Val-de-Marne
Country [36] 0 0
Germany
State/province [36] 0 0
Baden-Wurttemberg
Country [37] 0 0
Germany
State/province [37] 0 0
Bayern
Country [38] 0 0
Germany
State/province [38] 0 0
Hessen
Country [39] 0 0
Germany
State/province [39] 0 0
Niedersachsen
Country [40] 0 0
Germany
State/province [40] 0 0
Sachsen
Country [41] 0 0
Greece
State/province [41] 0 0
Thessaloniki
Country [42] 0 0
Israel
State/province [42] 0 0
Beer Sheva
Country [43] 0 0
Israel
State/province [43] 0 0
Haifa
Country [44] 0 0
Israel
State/province [44] 0 0
Holon
Country [45] 0 0
Israel
State/province [45] 0 0
Jerusalem
Country [46] 0 0
Israel
State/province [46] 0 0
Petah Tikva
Country [47] 0 0
Italy
State/province [47] 0 0
Campania
Country [48] 0 0
Italy
State/province [48] 0 0
Lazio
Country [49] 0 0
Italy
State/province [49] 0 0
Monza E Brianza
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
State/province [51] 0 0
Pavia
Country [52] 0 0
Mexico
State/province [52] 0 0
Veracruz
Country [53] 0 0
Mexico
State/province [53] 0 0
Huixquilucan
Country [54] 0 0
Mexico
State/province [54] 0 0
Mexico D.F
Country [55] 0 0
New Zealand
State/province [55] 0 0
Canterbury
Country [56] 0 0
New Zealand
State/province [56] 0 0
Auckland
Country [57] 0 0
Poland
State/province [57] 0 0
Dolnoslaskie
Country [58] 0 0
Poland
State/province [58] 0 0
Lubelskie
Country [59] 0 0
Poland
State/province [59] 0 0
Malopolskie
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Kemerovskaya Oblast
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Sankt-Peterburg
Country [62] 0 0
Sweden
State/province [62] 0 0
Uppsala Lan
Country [63] 0 0
Sweden
State/province [63] 0 0
Vastra Gotalands Lan
Country [64] 0 0
Turkey
State/province [64] 0 0
Izmir
Country [65] 0 0
Turkey
State/province [65] 0 0
Ankara
Country [66] 0 0
Turkey
State/province [66] 0 0
Antalya
Country [67] 0 0
Turkey
State/province [67] 0 0
Eskisehir
Country [68] 0 0
Turkey
State/province [68] 0 0
Istanbul
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Glasgow City
Country [70] 0 0
United Kingdom
State/province [70] 0 0
London, City Of
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04732221