Pulmonary Hypertension (World Health Organization Group 2)Phase 2Re-PHIRENCT05737940
A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2
A Phase 2 study testing AZD3427 in people with Pulmonary Hypertension (World Health Organization Group 2) and Heart Failure, run by AstraZeneca at 60 sites in 14 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Pulmonary Hypertension (World Health Organization Group 2), Heart Failure
- What is being tested?
- AZD3427
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 260 participants
- Where
- 60 sitesin 14 countries
- Study dates
- 24 Apr 2023to 25 Aug 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
60 sites in 14 countries.
60 sites in 14 countries
United States7 sites
Research Site
Baltimore, Maryland, 21287
Research Site
Beverly Hills, California, 90211
Research Site
La Jolla, California, 92093
Research Site
New Haven, Connecticut, 06519
Research Site
Omaha, Nebraska, 68198
Research Site
Rock Hill, South Carolina, 29732
Research Site
St Louis, Missouri, 63136
Canada7 sites
Research Site
Edmonton, Alberta, T6G 2E1
Research Site
Halifax, Nova Scotia, B3H 3A7
Research Site
London, Ontario, N6A 5A5
Research Site
Montreal, Quebec, H1T 1C8
Research Site
Ottawa, Ontario, K1Y 4W7
Research Site
Toronto, Ontario, M5G 2N2
Research Site
Vancouver, British Columbia, V6Z 1Y6
Japan7 sites
Research Site
Bunkyō City, 113-8603
Research Site
Kasugai-shi, 487-0016
Research Site
Kure-shi, 737-8505
Research Site
Nagoya, 466-8560
Research Site
Sapporo, 060-8648
Research Site
Sunto-gun, 411-8611
Research Site
Toyama, 930-0194
Italy6 sites
Research Site
Brescia, 25123
Research Site
Genoa, 16132
Research Site
Marche, 60126
Research Site
Milan, 20138
Research Site
Milan, 20142
Research Site
Trieste, 34149
Poland6 sites
Research Site
Bialystok, 15-276
Research Site
Gdansk, 80-952
Research Site
Krakow, 31-202
Research Site
Warsaw, 02-005
Research Site
Warsaw, 04-628
Research Site
Wroclaw, 50-556
China4 sites
Research Site
Beijing, 100034
Research Site
Changsha, 430033
Research Site
Guangzhou, 510100
Research Site
Kunming, 650051
Germany4 sites
Research Site
Berlin, 13353
Research Site
Cologne, 50937
Research Site
Frankfurt, 60596
Research Site
Jena, 07747
Spain4 sites
Research Site
Majadahonda, 28222
Research Site
Seville, 41009
Research Site
Toledo, 45007
Research Site
Valencia, 46026
Czechia3 sites
Research Site
Prague, 10034
Research Site
Prague, 12808
Research Site
Prague, 140 21
Netherlands3 sites
Research Site
Deventer, 7416 SE
Research Site
Heerlen, 6419 PC
Research Site
Tilburg, 5022 GC
United Kingdom3 sites
Research Site
Cambridge, CB2 0AY
Research Site
Clydebank, G81 4DY
Research Site
London, SW3 6NP
About this study
Official 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)
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
Read the detailed 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.
- Being tested
- AZD3427, Placebo
- Keywords
- Pulmonary Hypertension, Heart Failure, Left Heart Disease, WHO Group 2, Dose-ranging Study, Pulmonary vascular resistance
- Medical subject headings
- Hypertension, Pulmonary, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD3427Drug
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.
PlaceboDrug
The participants will receive SC injection of placebo single dose every 2 weeks for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| AZD3427 Dose A | Experimental | The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155. Receives: Drug: AZD3427 |
| AZD3427 Dose B | Experimental | The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155. Receives: Drug: AZD3427 |
| AZD3427 Dose C | Experimental | The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155. Receives: Drug: AZD3427 |
| Placebo | Placebo comparator | The participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Pulmonary Vascular Resistance (PVR)
The effect of AZD3427 compared with placebo on PVR parameter as measured by right heart catheterization (RHC-a procedure which allows measurement of blood pressure in the right side of the heart) after 24 weeks of treatment in participants with heart failure (HF) and pulmonary hypertension (PH) Group 2 was evaluated. PVR was calculated using formula, PVR=80* [Mean pulmonary arterial pressure[mPAP](mmHg)- Pulmonary artery wedge pressure[PAWP](mmHg)]/Cardiac output (L/min).
Baseline was defined as last non-missing value prior to or on the date of first study intervention dose. PVR was originally measured in dynes·sec/cm⁵. For the statistical analysis, PVR values were log-transformed, and change from baseline was assessed on the log-transformed scale. Results were subsequently back-transformed and presented on the original scale as the ratio of post-baseline to baseline PVR. Therefore, the unit of measure for this endpoint is a ratio.
The measure type is geometric mean ratio.
Measured: Baseline to Week 25
Secondary outcomes (22)
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP)
The effect of AZD3427 compared with placebo on mPAP parameter as measured by RHC after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Pulmonary Artery Wedge Pressure (PAWP)
The effect of AZD3427 compared with placebo on PAWP parameter as measured by RHC after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated.
Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention. PAWP was measured in mmHg. The analysis was done similar to the primary endpoint. Therefore, the unit of measure for this endpoint is a ratio.
The measure type is geometric mean ratio.
Measured: Baseline to Week 25
Change From Baseline in Cardiac Output (CO) ECHO
The effect of AZD3427 compared with placebo on CO parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Left Ventricular Stroke Volume (LV SV)
The effect of AZD3427 compared with placebo on LV SV parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
The effect of AZD3427 compared with placebo on EF parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Left Ventricular Global Longitudinal Strain (LVGLS)
The effect of AZD3427 compared with placebo on LVGLS parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. LVGLS is measured by echocardiograohy.
Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)
The effect of AZD3427 compared with placebo on PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Right Ventricle/Left Ventricle (RV/LV) Ratio
The effect of AZD3427 compared with placebo on RV/LV parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Right Ventricular Outflow Tract Acceleration Time (RVOT AT)
The effect of AZD3427 compared with placebo on RVOT AT parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Tricuspid Regurgitation Velocity (TRV)
The effect of AZD3427 compared with placebo on TRV parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. TRV was measured by Echocardiography.
Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in TAPSE/PASP [Tricuspid Annular Plane Systolic Excursion/ Pulmonary Arterial Systolic Pressure]
The effect of AZD3427 compared with placebo on TAPSE/PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Systemic Vascular Resistance (SVR)
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 was evaluated. SVR was measured by Echocardipgraphy.
Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in 6-minute Walking Distance (6MWD)
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS)
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 was evaluated. The score ranged from 0 to 100, where a higher score represents a better patient outcome. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Number of Participants With Improved Change From Baseline in New York Heart Association Functional Class (NYHA FC)
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 25
Change From Baseline in Serum Creatinine
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention. Creatinine was measured in micromoles/liter. The analysis was done similar to the primary endpoint. Therefore, the unit of measure for this endpoint is a ratio.
Measured: Baseline to Week 13 and Week 25
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention. NT-ProBNP was measured in picomole/Liter. The analysis was done similar to the primary endpoint. Therefore, the unit of measure for this endpoint is a ratio.
Measured: Baseline to Week 13 and Week 25
Change From Baseline in Cystatin C
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention. Cystatin C was measured in milligram/deciliter. The analysis was done similar to the primary endpoint. Therefore, the unit of measure for this endpoint is a ratio.
Measured: Baseline to Week 13 and Week 25
Change From Baseline in eGFR (Estimated Glomerular Filtration Rate)
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 was evaluated. Baseline was defined as the last non-missing value prior to or on the same date as the administration of the first dose of study intervention.
Measured: Baseline to Week 13 and Week 25
AZD3427 Serum Concentration
Serum concentration of AZD3427 was summarised by timepoints and dose level. This was done to evaluate the pharmacokinetics (PK) of AZD3427 after dosing in participants with HF and PH Group 2.
Considering the approximately 13-14 days half-life of AZD3427, low or non-quantifiable serum concentrations at Week 31 are not unexpected. Therefore, the presentation of the Week 31 results, including the reported NA values, reflects the prespecified statistical handling of the data and the observed concentration profile.
Measured: On Week 3, Week 5, Week 13, Week 19, Week 25 and Week 31
Number of Participants With Presence of Anti-drug Antibodies (ADAs)
The immunogenicity of AZD3427 was evaluated as measured by ADAs. The number of participants with treatment emergent (TE) ADA positive samples have been reported as they account for the ADA incidence during the study.
Measured: From Day 1 up to Day 211
Evaluation of Positive ADA Titer
The immunogenicity of AZD3427 as measured by ADAs was evaluated. ADA titer was summarized descriptively as a continuous variable, with median, minimum and maximum values.
The antibody titer for the TE-ADA positive (ADA incidence) participants have been reported. It is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA.
Combined timepoint is used in summary for subject-level overall ADA status (i.e. TE-ADA positive). The summary statistics were calculated based on the maximum post-baseline titre for each ADA-positive subject within each treatment group,'
Measured: At Day 1, Day 15, Day 29, Day 85, Day 169 and Day 211.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start24 Apr 2023
- Primary completion15 Jul 2025
- Study completion25 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Hypertension (World Health Organization Group 2)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737940
- Sponsor's protocol ID
- D8330C00003
- Acronym
- Re-PHIRE
- Status last verified
- Sep 2026
- First submitted
- 20 Jan 2023
- Last updated
- 27 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT05737940
- Acronym / sponsor ID
- Re-PHIRE / D8330C00003
- Keywords
- Pulmonary Hypertension, Heart Failure, Left Heart Disease, WHO Group 2, Dose-ranging Study, Pulmonary vascular resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 15 Jul 2025 (actual)
- Study completion
- 25 Aug 2025 (actual)
- First posted
- 21 Feb 2023 (actual)
- Results
- Posted 27 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AZD3427 Dose A | Experimental | Drug: AZD3427The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155. |
| AZD3427 Dose B | Experimental | Drug: AZD3427The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155. |
| AZD3427 Dose C | Experimental | Drug: AZD3427The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155. |
| Placebo | Placebo comparator | Drug: PlaceboThe participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Minimum body weight of 45 kg (inclusive).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD3427The participants will receive AZD3427 SC injection single dose of either Dose A or Dose B or Dose C every 2 weeks for 24 weeks. | Drug | AZD3427 Dose A, AZD3427 Dose B, AZD3427 Dose C |
| PlaceboThe participants will receive SC injection of placebo single dose every 2 weeks for 24 weeks. | Drug | Placebo |
Primary outcome
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Time frame: Baseline to Week 25
The effect of AZD3427 compared with placebo on PVR parameter as measured by right heart catheterization (RHC-a procedure which allows measurement of blood pressure in the right side of the heart) after 24 weeks of treatment in participants with heart failure (HF) and pulmonary hypertension (PH) Group 2 was evaluated. PVR was calculated using formula, PVR=80* [Mean pulmonary arterial pressure[mPAP](mmHg)- Pulmonary artery wedge pressure[PAWP](mmHg)]/Cardiac output (L/min). Baseline was defined as last non-missing value prior to or on the date of first study intervention dose. PVR was originally measured in dynes·sec/cm⁵. For the statistical analysis, PVR values were log-transformed, and change from baseline was assessed on the log-transformed scale. Results were subsequently back-transformed and presented on the original scale as the ratio of post-baseline to baseline PVR. Therefore, the unit of measure for this endpoint is a ratio. The measure type is geometric mean ratio.
22 secondary outcomes
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP)
Time frame: Baseline to Week 25
Change From Baseline in Pulmonary Artery Wedge Pressure (PAWP)
Time frame: Baseline to Week 25
Change From Baseline in Cardiac Output (CO) ECHO
Time frame: Baseline to Week 25
Change From Baseline in Left Ventricular Stroke Volume (LV SV)
Time frame: Baseline to Week 25
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline to Week 25
Change From Baseline in Left Ventricular Global Longitudinal Strain (LVGLS)
Time frame: Baseline to Week 25
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)
Time frame: Baseline to Week 25
Change From Baseline in Right Ventricle/Left Ventricle (RV/LV) Ratio
Time frame: Baseline to Week 25
Change From Baseline in Right Ventricular Outflow Tract Acceleration Time (RVOT AT)
Time frame: Baseline to Week 25
Change From Baseline in Tricuspid Regurgitation Velocity (TRV)
Time frame: Baseline to Week 25
Change From Baseline in TAPSE/PASP [Tricuspid Annular Plane Systolic Excursion/ Pulmonary Arterial Systolic Pressure]
Time frame: Baseline to Week 25
Change From Baseline in Systemic Vascular Resistance (SVR)
Time frame: Baseline to Week 25
Change From Baseline in 6-minute Walking Distance (6MWD)
Time frame: Baseline to Week 25
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS)
Time frame: Baseline to Week 25
Number of Participants With Improved Change From Baseline in New York Heart Association Functional Class (NYHA FC)
Time frame: Baseline to Week 25
Change From Baseline in Serum Creatinine
Time frame: Baseline to Week 13 and Week 25
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline to Week 13 and Week 25
Change From Baseline in Cystatin C
Time frame: Baseline to Week 13 and Week 25
Change From Baseline in eGFR (Estimated Glomerular Filtration Rate)
Time frame: Baseline to Week 13 and Week 25
AZD3427 Serum Concentration
Time frame: On Week 3, Week 5, Week 13, Week 19, Week 25 and Week 31
Number of Participants With Presence of Anti-drug Antibodies (ADAs)
Time frame: From Day 1 up to Day 211
Evaluation of Positive ADA Titer
Time frame: At Day 1, Day 15, Day 29, Day 85, Day 169 and Day 211.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- redacted CSPLink provided by the sponsor.
- redacted SAPLink provided by the sponsor.
- redacted CSR SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
60 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD3427 in people with Pulmonary Hypertension (World Health Organization Group 2) and Heart Failure, run by AstraZeneca at 60 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in United States, Canada, Japan, Italy, Poland and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Pulmonary Vascular Resistance (PVR) (time frame: Baseline to Week 25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.