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Completed

NCT Number: NCT05737940

A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2

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

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Key information

Conditions

Pulmonary Hypertension (World Health Organization Group 2) Cardiovascular Diseases Heart Diseases Heart Failure Hypertension Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Vascular Diseases

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Linz, Austria

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About this study

This study is a randomized, placebo-controlled, multi-centre, dose-ranging study of AZD3427 in participants with heart failure and pulmonary hypertension due to left heart disease (World Health Organisation [WHO] Group 2).

Approximately 220 participants will be randomised to 4 treatment groups (in a 1:1:1:1 ratio) to receive a subcutaneous (SC) injection of AZD3427 or placebo every 2 weeks for 24 weeks.

This study will evaluate 3 dose levels of AZD3427: Dose A, Dose B, and Dose C. Dose modification is not applicable for this study.

The study will be conducted in approximately 60 study centres across an estimated 15 countries.

The study will include approximately 16 study visits: 2 visits during the Screening Period,13 visits during the Treatment Period, and one visit during the Follow-up Period.

The expected total duration of the study is 32 to 37 weeks, depending on the length of the Screening Period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

AZD3427

Drug

The participants will receive AZD3427 SC injection single dose of either Dose A or Dose B or Dose C every 2 weeks for 24 weeks.

Placebo

Drug

The participants will receive SC injection of placebo single dose every 2 weeks for 24 weeks.

Primary outcomes

  1. Change from baseline in Pulmonary Vascular Resistance (PVR)

    Time frame: Baseline to Week 25

    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.

Secondary outcomes

  1. Change from baseline in Mean pulmonary arterial pressure (mPAP)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on mPAP parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  2. Change from baseline in Pulmonary artery wedge pressure (PAWP)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on PAWP parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  3. Change from baseline in cardiac output

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on cardiac output parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  4. Change from baseline in Stroke Volume (SV)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on SV parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  5. Change from baseline in Ejection fraction (EF)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on EF parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  6. Change from baseline in left ventricular global longitudinal strain (LVGLS)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on LVGLS parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  7. Change from baseline in pulmonary arterial systolic pressure (PASP)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  8. Change from baseline in right ventricle/left ventricle (RV/LV) ratio

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on RV/LV parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  9. Change from baseline in right ventricular outflow tract acceleration time (RVOT AT)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on RVOT AT parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  10. Change from baseline in Tricuspid regurgitation velocity (TRV)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on TRV parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  11. Change from baseline in TAPSE/PASP [Tricuspid annular plane systolic excursion/ Pulmonary arterial systolic pressure]

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on TAPSE/PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  12. Change from baseline in systemic vascular resistance

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on systemic vascular resistance parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  13. Change from baseline in 6-minute walking distance (6MWD)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on function and symptoms using 6MWD parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  14. Change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ TSS)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on function and symptoms using KCCQ TSS parameter after 24 weeks of treatment in participants with HF and PH Group 2. The score ranges from 0 to 100, where a higher score represents a better patient outcome.

  15. Change from baseline in New York Heart Association Functional Class (NYHA FC)

    Time frame: Baseline to Week 25

    To evaluate the effect of AZD3427 compared with placebo on function and symptoms using NYHA FC parameter after 24 weeks of treatment in participants with HF and PH Group 2.

  16. Change from baseline in serum creatinine

    Time frame: Baseline to Week 13 and Week 25

    To evaluate the effect of AZD3427 compared with placebo using serum creatinine parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.

  17. Change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)

    Time frame: Baseline to Week 13 and Week 25

    To evaluate the effect of AZD3427 compared with placebo using NT-proBNP parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.

  18. Change from baseline in cystatin C

    Time frame: Baseline to Week 13 and Week 25

    To evaluate the effect of AZD3427 compared with placebo using cystatin C parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.

  19. Change from baseline in eGFR (estimated glomerular filtration rate)

    Time frame: Baseline to Week 13 and Week 25

    To evaluate the effect of AZD3427 compared with placebo using eGFR parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.

  20. Pharmacokinetics (AZD3427 serum exposure)

    Time frame: On Day 15, Day 29, Day 85, Day 127, Day 169, and Day 211

    Serum concentration of AZD3427 summarised by timepoints and dose level.

  21. Number of participants with presence of Anti-drug antibodies (ADAs)

    Time frame: On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211

    To evaluate the immunogenicity of AZD3427 using ADA parameter.

  22. Evaluation of positive ADA titer

    Time frame: On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211

    To evaluate the immunogenicity of AZD3427 as measured by ADAs.

Other outcomes

  1. Number of participants with adverse events and serious adverse events

    Time frame: From Randomization (Day 1) up to Follow-up Visit (Day 211)

    To evaluate the safety and tolerability of AZD3427 as compared to placebo in participants with HF and PH Group 2

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Parexel

Registry information

Official study title

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)

Acronym: Re-PHIRE

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Feb 21, 2023
Registry last updated
Sep 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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