A Phase 2 Study of the Effects and Safety of PF-07328948 in Adults with Heart Failure (BRANCH-HF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Oct 2025 → ongoing

Decision date (initial)

2025-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-518438-94-00

ClinicalTrials.gov

NCT06991257

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic, Others

• To compare the effect of PF-07328948 versus placebo, administered daily over 36 weeks on clinical events (CV death, WHF event), physical function and symptoms in participants with HFmrEF/HFpEF.

Secondary objectives 4

1. • To compare the safety and tolerability of PF-07328948 versus placebo in participants with HFmrEF/HFpEF.
2. • To compare the effect of PF-07328948 versus placebo on HF disease-specific health status in participants with HFmrEF/HFpEF.
3. • To compare the effect of PF-07328948 versus placebo on physical function in participants with HFmrEF/HFpEF.
4. • To compare the effect of PF-07328948 versus placebo on a biomarker that assesses HF risk in participants with HFmrEF/HFpEF.

Conditions and MedDRA coding

Heart failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Male or female participants aged 18 years to < 80 years, at screening. a. Women of child-bearing potential can only be enrolled if a pregnancy test is negative at screening and randomization, and if they agree not to become pregnant or breastfeed while participating in this study. All fertile female participants must agree to use a highly effective method of contraception (permitted by protocol). b. Reproductive criteria for male and female participants are detailed in the main protocol.
2. 8. Receiving therapy with an SGLT2i for at least 30 days prior to randomization (V4). An SGLT2i run-in period is required for participants who are confirmed eligible for this study based on all other criteria but who are not currently prescribed an SGLT2i despite no history of prior intolerance/hypersensitivity or contraindication to an SGLT2i.
3. CPET substudy requirement: pVO2 less than 80% of the predicted normal value with RER ≥1.05 on Day 1 (V4). If a participant does not meet this pVO2 requirement on Day 1, that participant can continue with randomization as planned, but will not be included in the CPET substudy and will not undergo CPET during Week 36/V14 visit or ET visit.
4. 9. Signed and dated informed consent form before any trial-related activities.
5. 10. Willing and able to comply with all study visits and procedures detailed in the Schedule of Activities for the duration of the trial.
6. 2. Clinical diagnosis of chronic heart failure for at least 3 months prior to screening visit (V1), with each of the following criteria: • New York Heart Association (NYHA) Class II-IV at V1. • Left ventricular ejection fraction (LVEF) > 40% based on most recent assessment available in medical records.
7. 3. Evidence of the following on screening echocardiogram performed during V2, based on analysis by central reader: a. LVEF >40% b. If LVEF ≥50%, then one or more of the following structural heart abnormalities must be present: • Average E/e’ ≥11; • Left atrial (LA) volume index >34 mL/m2 • Left ventricular (LV) mass index ≥115 g/m2 for males and ≥95 g/m2 for females.
8. 4. Have at least one of the following: a. An elevated natriuretic peptide at screening (V1), analyzed by central laboratory, and defined as a NT-proBNP: • ≥300 ng/L for patients with body mass index (BMI) <30.0 kg/m2 in sinus rhythm; • ≥150 ng/L for patients with BMI ≥30.0 kg/m2 in sinus rhythm; • ≥600 ng/L for patients with BMI <30.0 kg/m2 in persistent or permanent atrial fibrillation; • ≥300 ng/L for patients with BMI ≥30.0 kg/m2 in persistent or permanent atrial fibrillation. b. Evidence for elevated cardiac filling pressures within 12 months of screening (V1) as defined by either: • Mean pulmonary capillary wedge pressure or LV end diastolic pressure (LVEDP) ≥15 mm Hg during catheterization at rest, or • Mean pulmonary capillary wedge pressure or LVEDP ≥25 mm Hg during catheterization performed during exercise, or • Pulmonary artery diastolic pressure measured by implantable monitor of ≥15 mm Hg c. Hospitalization with a primary diagnosis of decompensated HF requiring IV loop diuretic treatment within 12 months of screening (V1; but not within 1 month immediately prior to V1 or during the screening period). d. Urgent outpatient visit for worsening HF requiring IV loop diuretic treatment within 6 months of screening (V1, but not within 1 month immediately prior to V1 or during screening period). e. Oral diuretic intensification within 6 months of screening, defined as either a doubling of loop diuretic dose and/or new initiation of combination diuretic therapy to relieve congestion. Combination diuretic therapy could include: 1) new initiation of a thiazide-type diuretic (e.g., hydrochlorothiazide, metolazone, or chlorothiazide) plus a loop diuretic; or 2) new initiation of a mineralocorticoid receptor antagonist (e.g., spironolactone or eplerenone) OR SGLT2 inhibitor OR tolvaptan plus a loop diuretic.
9. 5. Able to perform the 6-minute walk test at screening (V1) with a minimum distance of 75 meters.
10. 6. KCCQ-23 TSS <85 at screening (V1).
11. 7. Have at least one of the following: a. BMI: ≥27.0 and <50.0 kg/m2 at screening (V1) b. Waist circumference >94 cm (37 inches) for males or >80 cm (31 inches) for females. c. Type 2 diabetes mellitus. d. Glycated hemoglobin (HbA1c) ≥5.7% (and < 10.0%) at screening (V1), analyzed by central laboratory e. Fasting serum triglyceride level ≥ 150 mg/dL (or ≥ 1.7 mmol/L) at screening (V2), analyzed by central laboratory

Exclusion criteria 28

1. 1. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. 28. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
3. 2. Any condition possibly affecting drug absorption (eg, prior or planned bariatric surgery, gastrectomy, or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency).
4. 10. Any other condition judged by the investigator to be the primary cause of dyspnea, including heart failure due to restrictive cardiomyopathy or infiltrative conditions (eg, amyloidosis, sarcoidosis), hypertrophic cardiomyopathy, complex congenital heart disease, primary pulmonary arterial hypertension, severe chronic obstructive pulmonary disease (eg, requiring long term supplemental oxygen), or right sided heart failure due to pulmonary disease.
5. 3. Any major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator (eg, knee replacement).
6. 4. Any of the following cardiovascular conditions: a. Acute coronary syndrome (including myocardial infarction), acute myocarditis, coronary artery bypass graft surgery, other major CV surgery, urgent percutaneous coronary intervention, cardiac resynchronization therapy, stroke, or transient ischemic attack within 3 months prior to screening (V1). b. Elective percutaneous coronary intervention within 30 days prior to screening (V1). c. Planned coronary, carotid or peripheral artery revascularization. d. Hospitalization for heart failure, or urgent outpatient visit for worsening HF requiring IV loop diuretic treatment, within 30 days prior to screening (V1) or during the screening period.
7. 5. History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous vasodilators and/or inotropes (eg, dobutamine, milrinone).
8. 6. Life-threatening or uncontrolled tachyarrhythmias at screening and/or randomization (V1-V4) including but not limited to sustained ventricular tachycardia and atrial fibrillation or atrial flutter with resting ventricular rate >110 bpm. -Applicable to EU only: Life-threating or uncontrolled tachyarrhythmias at screening and/or randomization (V1-V4) including but not limited to sustained ventricular tachycardia and atrial fibrillation or atrial flutter with resting ventricular rate >110 bpm.
9. 8. Type 1 diabetes mellitus.
10. 9. Prior intolerance/known hypersensitivity to an SGLT2i or contraindication to an SGLT2i. However, participants who demonstrate an intolerance/hypersensitivity to SGLT2i that prompts discontinuation during the protocol-specified run-in period may still proceed to randomization, following discussion with medical monitor.
11. 12. Active, untreated human immunodeficiency virus (HIV) or hepatitis infection, including hepatitis B and C.
12. 20. Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding screening (whichever is longer). Note: local regulations or other factors may require a washout period of more than 30 days.
13. 13. Liver cirrhosis.
14. 15. Renal disease requiring ongoing dialysis.
15. 16. Active malignancy requiring treatment (except for basal cell or squamous cell carcinomas of the skin).
16. 17. Any condition that would limit projected life-expectancy to less than 2 years in the clinical judgement of the investigator.
17. 18. Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s). The list of prohibited concomitant medications is provided in the main protocol.
18. 19. Current use of dietary supplements specifically intended to supplement BCAAs.
19. 7. Life-Threatening uncontrolled bradyarrhythmia including but not limited to a resting heart rate < 40 bpm, in the absence of a functioning pacemaker or implantable cardioverter defibrillator
20. 11. Presence of hemodynamically significant valvular heart disease (eg, moderate or severe valvular disease) in the opinion of the investigator.
21. 21. Prior participation in a trial involving PF-07328948.
22. 22. Systolic blood pressure >160 mm Hg, on two consecutive measurements performed at least 10 minutes apart, at screening (V1). [Note: a participant may be rescreened once if blood pressure control is subsequently established].
23. 23. Symptomatic hypotension with mean systolic blood pressure <90 mm Hg at screening (V1). [Note: a participant may be rescreened once if blood pressure control is subsequently established].
24. 25. Participants with ANY of the following abnormalities in clinical laboratory tests at Screening (V1, unless otherwise stated), as assessed by the central laboratory and confirmed by a single repeat test, if deemed necessary: • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥2 × upper limit of normal (ULN), or total bilirubin level ≥ 2 × ULN (unless in the setting of presumed Gilbert’s syndrome when total bilirubin level of ≥ 3 × ULN would be applied) • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, calculated using the CKD-EPI recommended serum creatinine-based formula • Fasting plasma glucose (FPG)>270 mg/dL (15 mmol/L) at V2 • Hemoglobin ≤9 g/dL • Urine albumin/creatinine ratio (UACR) ≥2200 mg/g • HbA1c ≥ 10.0%.
25. 26. A positive urine drug test at screening (V1). • Note: Participants who have been medically prescribed opiates/opioids, amphetamines or benzodiazepines and report the use of these drugs to the investigator at screening may be allowed to participate if approved by the sponsor.
26. 27. History of non-compliance to medical regimens or hospital visits.
27. 24. BMI >50.0 kg/m2 at screening (V1)
28. 29. Initiation and titration of a glucagon-like peptide-1 receptor agonist (GLP1-RA) within 24 weeks of enrollment with the express goal of obesity treatment. Change in GLP1-RA type or dose in a stable, pre-existing prescription does not represent an exclusion criterion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hierarchical combination of: • Adjudicated clinical events through Week 36: CV death, WHF event resulting in hospitalization, WHF event resulting in intravenous diuretic during an urgent HF visit, WHF event resulting in oral diuretic intensification in an outpatient setting. • CFB in 6MWD at Week 36 • CFB in KCCQ-23 TSS at Week 36.

Secondary endpoints 4

1. • Incidence of TEAEs and TESAEs.
2. • CFB in KCCQ-23 TSS, CSS, and physical limitation at Week 36.
3. • CFB in 6MWD at Week 36. • CPET substudy only: CFB in pVO2 at Week 36.
4. • CFB in NT-proBNP at Week 36.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 8

Locations

6 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications