PF-07328948 for Heart failure

Inclusion criteria

• {"criterion_text":"- 1.\tMale 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.\n- 6.\tKCCQ-23 TSS <85 at screening (V1).\n- 7.\tHave 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\n- 8.\tReceiving 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.\n- 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.\n- 9.\tSigned and dated informed consent form before any trial-related activities.\n- 10.\tWilling and able to comply with all study visits and procedures detailed in the Schedule of Activities for the duration of the trial.\n- 2.\tClinical 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.\n- 3.\tEvidence of the following on screening echocardiogram performed during V2, based on analysis by central reader: a.\tLVEF >40% b.\tIf LVEF ≥50%, then one or more of the following structural heart abnormalities must be present: •\tAverage E/e’ ≥11; •\tLeft atrial (LA) volume index >34 mL/m2 •\tLeft ventricular (LV) mass index ≥115 g/m2 for males and ≥95 g/m2 for females.\n- 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: •\t≥300 ng/L for patients with body mass index (BMI) <30.0 kg/m2 in sinus rhythm; •\t≥150 ng/L for patients with BMI ≥30.0 kg/m2 in sinus rhythm; •\t≥600 ng/L for patients with BMI <30.0 kg/m2 in persistent or permanent atrial fibrillation; •\t≥300 ng/L for patients with BMI ≥30.0 kg/m2 in persistent or permanent atrial fibrillation. b.\tEvidence for elevated cardiac filling pressures within 12 months of screening (V1) as defined by either: •\tMean pulmonary capillary wedge pressure or LV end diastolic pressure (LVEDP) ≥15 mm Hg during catheterization at rest, or •\tMean pulmonary capillary wedge pressure or LVEDP ≥25 mm Hg during catheterization performed during exercise, or •\tPulmonary artery diastolic pressure measured by implantable monitor of ≥15 mm Hg c.\tHospitalization 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.\tUrgent 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.\n- 5.\tAble to perform the 6-minute walk test at screening (V1) with a minimum distance of 75 meters."}

Exclusion criteria

• {"criterion_text":"- 1.\tAny 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.\n- 9.\tPrior 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.\n- 12.\tActive, untreated human immunodeficiency virus (HIV) or hepatitis infection, including hepatitis B and C.\n- 20.\tPrevious 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.\n- 13.\tLiver cirrhosis.\n- 15.\tRenal disease requiring ongoing dialysis.\n- 16.\tActive malignancy requiring treatment (except for basal cell or squamous cell carcinomas of the skin).\n- 17.\tAny condition that would limit projected life-expectancy to less than 2 years in the clinical judgement of the investigator.\n- 18.\tCurrent 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.\n- 19.\tCurrent use of dietary supplements specifically intended to supplement BCAAs.\n- 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\n- 28.\tInvestigator 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.\n- 20.\t11.\tPresence of hemodynamically significant valvular heart disease (eg, moderate or severe valvular disease) in the opinion of the investigator.\n- 21.\tPrior participation in a trial involving PF-07328948.\n- 22.\tSystolic 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].\n- 23.\tSymptomatic 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].\n- 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%.\n- 26.\tA 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.\n- 27.\tHistory of non-compliance to medical regimens or hospital visits.\n- 24. BMI >50.0 kg/m2 at screening (V1)\n- 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.\n- 2.\tAny 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).\n- 10.\tAny 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.\n- 3.\tAny major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator (eg, knee replacement).\n- 4.\tAny of the following cardiovascular conditions: a.\tAcute 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.\tElective percutaneous coronary intervention within 30 days prior to screening (V1). c.\tPlanned coronary, carotid or peripheral artery revascularization. d.\tHospitalization 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.\n- 5.\tHistory 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).\n- 6.\tLife-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.\n- 8.\tType 1 diabetes mellitus."}

Primary endpoints

• {"endpoint_text":"- Hierarchical combination of: •\tAdjudicated 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. •\tCFB in 6MWD at Week 36 •\tCFB in KCCQ-23 TSS at Week 36.","definition_or_measurement_approach":"Composite hierarchical endpoint: adjudicated clinical events through Week 36 (CV death; worsening heart failure [WHF] events causing hospitalization, WHF events resulting in IV diuretic during urgent HF visit, WHF events resulting in oral diuretic intensification in outpatient setting). Change from baseline (CFB) in 6-minute walk distance (6MWD) at Week 36. Change from baseline in KCCQ-23 total symptom score (TSS) at Week 36."}

Secondary endpoints

• {"endpoint_text":"- •\tIncidence of TEAEs and TESAEs.","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) collected and reported per safety reporting procedures."}
• {"endpoint_text":"- •\tCFB in KCCQ-23 TSS, CSS, and physical limitation at Week 36.","definition_or_measurement_approach":"Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ-23) Total Symptom Score (TSS), Clinical Summary Score (CSS), and physical limitation domain at Week 36."}
• {"endpoint_text":"- •\tCFB in 6MWD at Week 36. •\tCPET substudy only: CFB in pVO2 at Week 36.","definition_or_measurement_approach":"Change from baseline in 6-minute walk distance (6MWD) at Week 36. For CPET substudy, change from baseline in peak VO2 (pVO2) at Week 36 measured by CPET (central read specified)."}
• {"endpoint_text":"- •\tCFB in NT-proBNP at Week 36.","definition_or_measurement_approach":"Change from baseline in NT-proBNP (central laboratory measurement) at Week 36."}

Methods

• Patient brochure (country-specific K2 recruitment material) - printed distribution to target patients with heart failure
• Patient flyer (country-specific K3 recruitment material) - printed distribution and clinic handouts targeting potential participants
• Patient invite letter (country-specific K4 recruitment material) - mailed or clinic-distributed invitation to eligible patients
• Video QR Post Card (K5) and Video Script (K6) - digital video recruitment via QR code linking to study information
• K1 Recruitment Arrangements documents (country-specific) describing local recruitment procedures and materials

Spain

Earliest CTIS Part Ii Submission Date

22-07-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

252

Number Of Sites

11

Number Of Participants

103

Poland

Earliest CTIS Part Ii Submission Date

24-09-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

188

Number Of Sites

7

Number Of Participants

50

Czechia

Earliest CTIS Part Ii Submission Date

17-09-2025

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

194

Number Of Sites

8

Number Of Participants

73

Bulgaria

Earliest CTIS Part Ii Submission Date

17-09-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

195

Number Of Sites

13

Number Of Participants

50

France

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

201

Number Of Sites

4

Number Of Participants

30

Hungary

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

202

Number Of Sites

8

Number Of Participants

50

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Regulatory / clinical trial support (sponsor duties code 7)

Name

Icon Clinical Research Limited

Responsibilities

Laboratory/site support (sponsor duties code 4)

Name

Syneos Health Inc.

Responsibilities

Laboratory/sample support (sponsor duties code 4)

Name

Premier Research International LLC

Responsibilities

Dictionary Coding (enterprise level vendor)

Third parties

• {"country":"United States","full_name":"Massachusetts General Hospital","duties_or_roles":"CPET central review","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Baim Institute For Clinical Research Inc.","duties_or_roles":"CEC Adjudication; Adjudication Events Process; ECHO central reads; Independent Oversight Committee Support – DMSB","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Regulatory / clinical trial support (sponsor duties code 7)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Laboratory site support (sponsor duties code 4)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Laboratory/sample support (sponsor duties code 4)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"Laboratory testing (sponsor duties code 4)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Biospecimen Management / Long Term Storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"Dictionary Coding (enterprise level vendor)","organisation_type":"Pharmaceutical company"}