A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2
Re-PHIRE
A Phase IIb Randomised, Double-blind, Placebo-controlled, Multi-centre, Dose-ranging Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Due to Left Heart Disease (WHO Group 2)
1 other identifier
interventional
260
14 countries
60
Brief Summary
This study is intended to assess the ability of AZD3427 to reduce pulmonary vascular resistance (PVR) after 24 weeks of treatment in participants with heart failure (HF) and pulmonary hypertension (PH) Group 2
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2023
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2023
CompletedFirst Posted
Study publicly available on registry
February 21, 2023
CompletedStudy Start
First participant enrolled
April 24, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
August 25, 2025
CompletedSeptember 24, 2025
September 1, 2025
2.2 years
January 20, 2023
September 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change from baseline in Pulmonary Vascular Resistance (PVR)
To evaluate the effect of AZD3427 on PVR parameter compared with placebo as measured by right heart catheterization (RHC) after 24 weeks of treatment in participants with HF and PH Group 2.
Baseline to Week 25
Secondary Outcomes (22)
Change from baseline in Mean pulmonary arterial pressure (mPAP)
Baseline to Week 25
Change from baseline in Pulmonary artery wedge pressure (PAWP)
Baseline to Week 25
Change from baseline in cardiac output
Baseline to Week 25
Change from baseline in Stroke Volume (SV)
Baseline to Week 25
Change from baseline in Ejection fraction (EF)
Baseline to Week 25
- +17 more secondary outcomes
Other Outcomes (1)
Number of participants with adverse events and serious adverse events
From Randomization (Day 1) up to Follow-up Visit (Day 211)
Study Arms (4)
AZD3427 Dose A
EXPERIMENTALThe participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155.
AZD3427 Dose B
EXPERIMENTALThe participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155.
AZD3427 Dose C
EXPERIMENTALThe participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155.
Placebo
PLACEBO COMPARATORThe participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155.
Interventions
Eligibility Criteria
You may qualify if:
- Participant must be ≥ 18 years of age inclusive.
- Participants must have a pre-existing diagnosis of HF, NYHA function class (FC) II to IV, and a pre-existing diagnosis of PH-LHD or likely or intermediate probability of Pulmonary hypertension due to left heart disease (PH-LHD) as per 2022 Pulmonary hypertension due to left heart disease European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. Participants must be on stable HF standard of care medication, including diuretics.
- Participants must have a combination of echocardiographic parameters that show intermediate or high probability of PH as per 2022 ESC/ERS guidelines.
- Participants must have an on-study elevated pulmonary artery pressure from RHC performed as per RHC manual provided by the Sponsor, at Screening Visit 2:
- PAWP ≥ 15 mmHg
- mPAP ≥ 20 mmHg
- Minimum body weight of 45 kg (inclusive).
- Capable and willing of giving signed informed consent.
You may not qualify if:
- Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.
- Historical or current evidence of a clinically significant disease or disorder.
- Decompensated HF or hospitalisation due to decompensated HF.
- Any contraindications to RHC.
- History of hypersensitivity to SC injections or devices.
- History of hypersensitivity to drugs with a similar chemical structure or class to AZD3427 or any component of AZD3427 drug product, or ongoing clinically important allergy/hypersensitivity.
- Known lung disease with Forced expiratory volume in the first second (FEV1) \< 30% of predicted.
- Congenital long QT syndrome.
- Cardiac ventricular arrhythmia which requires treatment. Participants with atrial fibrillation or flutter and controlled ventricular rate are permitted.
- History of or anticipated heart transplant or ventricular assist device implantation.
- Any known planned (scheduled) highly invasive Cardiovascular (CV) procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
- Participants who have previously received AZD3427.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
Study Sites (60)
Research Site
Beverly Hills, California, 90211, United States
Research Site
La Jolla, California, 92093, United States
Research Site
New Haven, Connecticut, 06519, United States
Research Site
Baltimore, Maryland, 21287, United States
Research Site
St Louis, Missouri, 63136, United States
Research Site
Omaha, Nebraska, 68198, United States
Research Site
Rock Hill, South Carolina, 29732, United States
Research Site
Linz, 4020, Austria
Research Site
Vienna, 1100, Austria
Research Site
Edmonton, Alberta, T6G 2E1, Canada
Research Site
Vancouver, British Columbia, V6Z 1Y6, Canada
Research Site
Halifax, Nova Scotia, B3H 3A7, Canada
Research Site
London, Ontario, N6A 5A5, Canada
Research Site
Ottawa, Ontario, K1Y 4W7, Canada
Research Site
Toronto, Ontario, M5G 2N2, Canada
Research Site
Montreal, Quebec, H1T 1C8, Canada
Research Site
Beijing, 100034, China
Research Site
Changsha, 430033, China
Research Site
Guangzhou, 510100, China
Research Site
Kunming, 650051, China
Research Site
Prague, 10034, Czechia
Research Site
Prague, 12808, Czechia
Research Site
Prague, 140 21, Czechia
Research Site
Aarhus, 8200, Denmark
Research Site
Copenhagen, 2100, Denmark
Research Site
Berlin, 13353, Germany
Research Site
Cologne, 50937, Germany
Research Site
Frankfurt, 60596, Germany
Research Site
Jena, 07747, Germany
Research Site
Brescia, 25123, Italy
Research Site
Genoa, 16132, Italy
Research Site
Marche, 60126, Italy
Research Site
Milan, 20138, Italy
Research Site
Milan, 20142, Italy
Research Site
Trieste, 34149, Italy
Research Site
Bunkyō City, 113-8603, Japan
Research Site
Kasugai-shi, 487-0016, Japan
Research Site
Kure-shi, 737-8505, Japan
Research Site
Nagoya, 466-8560, Japan
Research Site
Sapporo, 060-8648, Japan
Research Site
Sunto-gun, 411-8611, Japan
Research Site
Toyama, 930-0194, Japan
Research Site
Deventer, 7416 SE, Netherlands
Research Site
Heerlen, 6419 PC, Netherlands
Research Site
Tilburg, 5022 GC, Netherlands
Research Site
Bialystok, 15-276, Poland
Research Site
Gdansk, 80-952, Poland
Research Site
Krakow, 31-202, Poland
Research Site
Warsaw, 02-005, Poland
Research Site
Warsaw, 04-628, Poland
Research Site
Wroclaw, 50-556, Poland
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Majadahonda, 28222, Spain
Research Site
Seville, 41009, Spain
Research Site
Toledo, 45007, Spain
Research Site
Valencia, 46026, Spain
Research Site
Gothenburg, 413 45, Sweden
Research Site
Huddinge, 141 57, Sweden
Research Site
Cambridge, CB2 0AY, United Kingdom
Research Site
Clydebank, G81 4DY, United Kingdom
Research Site
London, SW3 6NP, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2023
First Posted
February 21, 2023
Study Start
April 24, 2023
Primary Completion
July 15, 2025
Study Completion
August 25, 2025
Last Updated
September 24, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.