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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05492500




Registration number
NCT05492500
Ethics application status
Date submitted
25/07/2022
Date registered
8/08/2022

Titles & IDs
Public title
A Study of Ponsegromab in People With Heart Failure
Scientific title
A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 4-ARM STUDY TO INVESTIGATE SYMPTOMS, FUNCTION, HEALTH-RELATED QUALITY OF LIFE AND SAFETY WITH REPEATED SUBCUTANEOUS ADMINISTRATION OF PONSEGROMAB VERSUS PLACEBO IN ADULT PARTICIPANTS WITH HEART FAILURE
Secondary ID [1] 0 0
2022-001809-50
Secondary ID [2] 0 0
C3651011
Universal Trial Number (UTN)
Trial acronym
GARDEN TIMI 74
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Main cohort (Cohort A): Ponsegromab low dose
Treatment: Drugs - Main cohort (Cohort A): Ponsegromab medium dose
Treatment: Drugs - Main cohort (Cohort A): ponsegromab high dose
Other interventions - Main cohort (Cohort A): Matched placebo
Treatment: Drugs - Open-label, PK Cohort (Cohort B): ponsegromab low dose
Treatment: Drugs - Open-label, PK Cohort (Cohort B): ponsegromab medium dose
Treatment: Drugs - Open-label, PK Cohort (Cohort B): ponsegromab high dose
Treatment: Drugs - Optional Cohort C: Ponsegromab low dose
Other interventions - Optional Cohort C: Matched placebo
Treatment: Drugs - Optional Cohort D: Ponsegromab high dose
Other interventions - Optional Cohort D: Matched placebo

Experimental: Main cohort (Cohort A): ponsegromab low dose - Participants will receive a low dose Q4W SC

Experimental: Main cohort (Cohort A): ponsegromab medium dose - Participants will receive a medium dose Q4W SC

Experimental: Main cohort (Cohort A): ponsegromab high dose - Participants will receive a high dose Q4W SC

Placebo comparator: Main cohort (Cohort A): placebo - matched placebo

Experimental: Open-label, PK Cohort (Cohort B): ponsegromab low dose - Participants will receive a low dose Q4W SC

Experimental: Open-label, PK Cohort (Cohort B): ponsegromab medium dose - Participants will receive a medium dose Q4W SC

Experimental: Open-label, PK Cohort (Cohort B): ponsegromab high dose - Participants will receive a high dose Q4W SC

Experimental: Optional Cohort C: ponsegromab low dose - Participants will receive a low dose Q4W SC

Placebo comparator: Optional Cohort C: placebo - matched placebo

Experimental: Optional Cohort D: ponsegromab high dose - Participants will receive a high dose Q4W SC

Placebo comparator: Optional Cohort D: placebo - matched placebo


Treatment: Drugs: Main cohort (Cohort A): Ponsegromab low dose
Ponsegromab low dose subcutaneous injection

Treatment: Drugs: Main cohort (Cohort A): Ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection

Treatment: Drugs: Main cohort (Cohort A): ponsegromab high dose
Ponsegromab high dose subcutaneous injection

Other interventions: Main cohort (Cohort A): Matched placebo
Matched placebo subcutaneous injection

Treatment: Drugs: Open-label, PK Cohort (Cohort B): ponsegromab low dose
ponsegromab low dose subcutaneous injection

Treatment: Drugs: Open-label, PK Cohort (Cohort B): ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection

Treatment: Drugs: Open-label, PK Cohort (Cohort B): ponsegromab high dose
Ponsegromab high dose subcutaneous injection

Treatment: Drugs: Optional Cohort C: Ponsegromab low dose
Ponsegromab low dose subcutaneous injection

Other interventions: Optional Cohort C: Matched placebo
Matched placebo subcutaneous injection

Treatment: Drugs: Optional Cohort D: Ponsegromab high dose
Ponsegromab high dose subcutaneous injection

Other interventions: Optional Cohort D: Matched placebo
Matched placebo subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score
Timepoint [1] 0 0
baseline, 22 weeks
Secondary outcome [1] 0 0
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score
Timepoint [1] 0 0
baseline, 22 weeks
Secondary outcome [2] 0 0
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score
Timepoint [2] 0 0
baseline, 22 weeks
Secondary outcome [3] 0 0
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain
Timepoint [3] 0 0
baseline, 22 weeks
Secondary outcome [4] 0 0
Main cohort (Cohort A): Responses as defined by a =5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score
Timepoint [4] 0 0
baseline, 22 weeks
Secondary outcome [5] 0 0
Main cohort (Cohort A): Responses as defined by a =5 point increase from baseline in Overall Summary Score
Timepoint [5] 0 0
baseline, 22 weeks
Secondary outcome [6] 0 0
Main cohort (Cohort A): Responses as defined by a =5 point increase from baseline in Total Symptom Score
Timepoint [6] 0 0
baseline, 22 weeks
Secondary outcome [7] 0 0
Main cohort (Cohort A): Responses as defined by a =5 point increase from baseline in physical limitation
Timepoint [7] 0 0
baseline, 22 weeks
Secondary outcome [8] 0 0
Main cohort (Cohort A): Change from baseline in 6-Minute Walk Distance
Timepoint [8] 0 0
baseline, 22 weeks
Secondary outcome [9] 0 0
Main cohort (Cohort A): Change from baseline in PROMIS-Fatigue 7a which will be completed by study participants on an electronic device, so as to compare the effect of ponsegromab versus placebo on fatigue as reported by participants with HF
Timepoint [9] 0 0
baseline, 22 weeks
Secondary outcome [10] 0 0
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent adverse events
Timepoint [10] 0 0
32 weeks
Secondary outcome [11] 0 0
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent serious adverse events
Timepoint [11] 0 0
32 weeks
Secondary outcome [12] 0 0
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal laboratory results
Timepoint [12] 0 0
32 weeks
Secondary outcome [13] 0 0
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal vital signs
Timepoint [13] 0 0
32 weeks
Secondary outcome [14] 0 0
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent adverse events
Timepoint [14] 0 0
22 weeks
Secondary outcome [15] 0 0
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent serious adverse events
Timepoint [15] 0 0
22 weeks
Secondary outcome [16] 0 0
Open-Label, PK Cohort (Cohort B): Incidence of abnormal laboratory results
Timepoint [16] 0 0
22 weeks
Secondary outcome [17] 0 0
Open-Label, PK Cohort (Cohort B): Incidence of abnormal vital signs
Timepoint [17] 0 0
22 weeks

Eligibility
Key inclusion criteria
* Male and female participants aged 18 years or older

-. Clinical evidence of HF with each of the following criteria:
1. 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).
2. NYHA class II-IV at screening.
3. NT-proBNP =400 pg/mL at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]).
* Serum GDF-15 concentration =2000 pg/mL at screening.
* Cohort D only: Serum GDF-15 concentration <2000 pg/mL at screening.
* KCCQ-23 CSS <75 at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]).
* Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]):

1. Non-edematous unintentional weight loss =5% in the last 6 months or current BMI <20 kg/m2, associated with subjective fatigue or anorexia; or
2. 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
3. A score of <60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
* 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 (Cohort B) only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.

* History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
* Acute coronary syndrome within 1 month prior to randomization.
* 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 (Cohort B) only: coronary revascularization more than 1 month prior to randomization is permitted.

* Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
* Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
* Previous exposure to ponsegromab in a prior clinical study.
* Renal disease requiring ongoing dialysis.
* 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).

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
27/05/2026
Actual
Sample size
Target
781
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Core Research Group - Brisbane
Recruitment hospital [3] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [5] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4064 - Brisbane
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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North Carolina
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United States of America
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Oklahoma
Country [15] 0 0
United States of America
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Texas
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Canada
State/province [16] 0 0
British Columbia
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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China
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Beijing
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China
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Guangdong
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China
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Hunan
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China
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Jilin
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China
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Shaanxi
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China
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China
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Shanghai
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China
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Shanxi
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China
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Tianjin
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Czechia
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Jihomoravský KRAJ
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Czechia
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Náchod
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Czechia
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Praha 4
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Czechia
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Praha 10
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Czechia
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Praha 2
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Czechia
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Praha 6
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Nordrhein-westfalen
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Germany
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Sachsen
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Germany
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Thuringia
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Germany
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Thüringen
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Hungary
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Baranya
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Hungary
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Bács-kiskun
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Hungary
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Békés
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Hungary
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Gyor-moson-sopron
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Hungary
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Nyíregyháza
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Hungary
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Somogy
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Hungary
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Budapest
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Nagykanizsa
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Japan
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Hyogo
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Iwate
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Miyagi
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Osaka
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Saitama
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Tokyo
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Kumamoto
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Poland
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Dolnoslaskie
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Mazowieckie
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Podlaskie
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Pomorskie
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Warminsko-mazurskie
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Wielkopolskie
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Lodz
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Tychy
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Warsaw
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Warszawa
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Poland
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Slaskie
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Spain
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A Coruña [LA Coruña]
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Spain
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Barcelona [barcelona]
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Spain
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Barcelona
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Spain
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Catalunya [cataluña]
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Spain
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Madrid, Comunidad DE
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Spain
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Murcia, Región DE
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Spain
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Valenciana, Comunitat
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Spain
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Granada
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Oviedo
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Spain
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Sevilla
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Spain
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Valencia
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United Kingdom
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Buckinghamshire
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United Kingdom
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Dundee CITY
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United Kingdom
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England AND Wales
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United Kingdom
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London, CITY OF
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United Kingdom
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Scotland
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United Kingdom
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Barnet
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United Kingdom
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Cambridge
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United Kingdom
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Clydebank
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United Kingdom
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Lincoln
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United Kingdom
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Liverpool
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United Kingdom
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Sheffield
Country [91] 0 0
United Kingdom
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Stockton-On-Tees

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Thrombolysis In Myocardial Infarction (TIMI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05492500