A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2 (Re-PHIRE)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Pulmonary Hypertension (World Health Organization Group 2); Heart Failure

Treatments: Drug: AZD3427; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05737940

D8330C00003

Details and patient eligibility

About

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

Full description

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

1. Participant must be ≥ 18 years of age inclusive.

2. 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.

3. Participants must have a combination of echocardiographic parameters that show intermediate or high probability of PH as per 2022 ESC/ERS guidelines.

4. 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:

   1. PAWP ≥ 15 mmHg
   2. mPAP ≥ 20 mmHg

5. Minimum body weight of 45 kg (inclusive).

6. Capable and willing of giving signed informed consent.

Exclusion Criteria

1. Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.
2. Historical or current evidence of a clinically significant disease or disorder.
3. Decompensated HF or hospitalisation due to decompensated HF.
4. Any contraindications to RHC.
5. History of hypersensitivity to SC injections or devices.
6. 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.
7. Known lung disease with Forced expiratory volume in the first second (FEV1) < 30% of predicted.
8. Congenital long QT syndrome.
9. Cardiac ventricular arrhythmia which requires treatment. Participants with atrial fibrillation or flutter and controlled ventricular rate are permitted.
10. History of or anticipated heart transplant or ventricular assist device implantation.
11. Any known planned (scheduled) highly invasive Cardiovascular (CV) procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
12. Participants who have previously received AZD3427.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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220 participants in 4 patient groups, including a placebo group

AZD3427 Dose A

Experimental group

Description:

The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155.

Treatment:

Drug: AZD3427

AZD3427 Dose B

Experimental group

Description:

The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155.

Treatment:

Drug: AZD3427

AZD3427 Dose C

Experimental group

Description:

The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155.

Treatment:

Drug: AZD3427

Placebo

Placebo Comparator group

Description:

The participants will receive single dose placebo every 2 weeks for 24 weeks from Day 1 to Day 155.

Treatment:

Drug: Placebo