A Phase 2 Study of the Effects of Ponsegromab on Health-Related Qualityof Life and Safety in Patients With Heart Failure (GARDEN-TIMI 74)

Phase 1

• Conditions: Heart failure; MedDRA version: 20.0Level: HLGTClassification code 10019280Term: Heart failuresSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2022-001809-50-DE
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-21
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 436

Inclusion Criteria

Age and Sex:
1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.
a. A female participant is eligible to participate if she is not pregnant or breastfeeding.
b. To refer to Appendix 4 of Protocol for reproductive criteria for male (Section 10.4.1 of Protocol) and female (Section 10.4.2 of Protocol) participants.
Disease Characteristics:
2. Clinical evidence of HF with each of the following criteria:
a. LVEF <50% on most recent measurement, within 12 months of screening.
Note: An assessment of LVEF in the prior 12 months is not required in
situations where LVEF has been persistently <50% on prior assessments
obtained at least 3 months apart (including the most recent
measurement).
b. NYHA class II-IV at screening.
c. Main cohort only:NT-proBNP =400 pg/mL at screening.
3. Serum GDF-15 concentration =2000 pg/mL at screening.
4. Main cohort only: KCCQ-23 CSS <75 at screening.
5. Main cohort only: Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening:
a. Non-edematous unintentional weight loss =5% in the last 6 months or current BMI <20 kg/m2, associated with subjective fatigue or anorexia; or
b. Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks based on the KCCQ-23 administered at screening; or
c. A score of <60 on the Physical Limitations Domain of the KCCQ-23
administered at screening.
6. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures (including but not limited to subcutaneous injection of study intervention).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 218
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 218

Exclusion Criteria

Medical Conditions:
1. Acute decompensated HF within 1 month prior to SV1 or during the screening period.
2. Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial.
* For the open-label, PK cohort only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.
3. History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
4. Acute coronary syndrome within 1 month prior to randomization.
5. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial.
• For the open-label, PK cohort only: coronary revascularization more than 1 month prior to randomization is permitted.
6. Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (i.e, tachyarrhythmia or bradyarrhythmia).
7. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody.
8. Other medical (eg, severe, uncorrected aortic stenosis; active malignancy) or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, may limit life expectancy to less than 1 year and / or make the participant inappropriate for the study.
9. Current use of any prohibited concomitant medication(s). To refer to Section 6.9 of Protocol.
10. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Treatment with an investigational biotherapeutic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
11. Previous exposure to ponsegromab in a prior clinical study.
12. Renal disease requiring ongoing dialysis.
13. Cirrhosis with evidence of portal hypertension not due to HF or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT Level = 3 x ULN, or total bilirubin level = 2 x ULN (unless history of Gilbert's syndrome).
14. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
15.Open-label, PK Cohort: At certain sites in the US and Canada, where permitted, participants who fail to qualify for the main cohort may be eligible for participation in a separate open-label, PK cohort.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified