Heart Failure
Conditions
Keywords
Heart Failure, N-terminal pro-B type natriuretic peptide, Kansas City Cardiomyopathy Questionnaire, Patient's Global Impression of Severity, Patient's Global Impression of Change, Patient Reported Outcome Measurement Information System, Growth differentiation factor 15, New York Heart Association
Brief summary
The primary purpose of this clinical trial is to compare the effects of study medicine (Ponsegromab/PF-06946860) with a placebo (an injection that looks like the study medicine but does not contain the active medicine) to find out if the study medicine is better than the placebo (an injection that looks like the study medicine but does not contain the active medicine) for treatment of symptoms related to heart failure. Participants will not know which treatment group they are assigned to. Most participants in this study will receive the study medicine or placebo by shots under the skin every four weeks. People may be able to participate in this study if they have heart failure. Participants will take part in this study for about 9 months. During this time participants will visit the study clinic once a month. A separate PK cohort within this clinical trial will receive open-label study medicine (Ponsegromab/PF-06946860) only. Participants in this open-label, PK cohort will not receive placebo. These participants will receive the study medicine by shots under the skin every four weeks. People may be able to participate in this study cohort if they also have heart failure. Participants will take part in the open-label, PK cohort for about 7 months.
Detailed description
The primary purpose of this study is to assess the effect of repeated subcutaneous administration of ponsegromab (PF-06946860) compared to placebo on frequency, severity, and burden of symptoms as well as physical limitations in participants with heart failure and different ranges of circulating GDF-15 concentrations. The study will also assess the safety, tolerability, PK, PD, and immunogenicity of ponsegromab. A separate, open-label, PK cohort, with more frequent PK and GDF-15 collection after single and multiple subcutaneous administration of ponsegromab (PF-06946860), will be enrolled at certain sites to facilitate a more comprehensive assessment of PK characteristics and PK/PD relationship for GDF-15 in participants with heart failure and elevated circulating GDF-15 concentrations.
Interventions
DRUGMain cohort (Cohort A): Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
DRUGMain cohort (Cohort A): Ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
DRUGMain cohort (Cohort A): ponsegromab high dose
Ponsegromab high dose subcutaneous injection
OTHERMain cohort (Cohort A): Matched placebo
Matched placebo subcutaneous injection
DRUGOpen-label, PK Cohort (Cohort B): ponsegromab low dose
ponsegromab low dose subcutaneous injection
DRUGOpen-label, PK Cohort (Cohort B): ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
DRUGOpen-label, PK Cohort (Cohort B): ponsegromab high dose
Ponsegromab high dose subcutaneous injection
DRUGOptional Cohort C: Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
OTHEROptional Cohort C: Matched placebo
Matched placebo subcutaneous injection
DRUGOptional Cohort D: Ponsegromab high dose
Ponsegromab high dose subcutaneous injection
OTHEROptional Cohort D: Matched placebo
Matched placebo subcutaneous injection
Sponsors
Pfizer
The TIMI Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
In the main cohort (Cohort A), Cohort C and Cohort D, investigators, sponsor, participants and other site staff will be blinded to participants' assigned study intervention, including the site staff assigned to prepare and administer the study intervention. Pharmacists and site personnel will be blinded to study intervention versus placebo within each study arm. The separate PK cohort (Cohort B) will be open-label and study treatment will be prepared and administered as per treatment assignment by qualified personnel. There is no blinding in the open-label, PK cohort (Cohort B).
Intervention model description
In the main cohort (Cohort A), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab or placebo. In optional Cohort C, ponsegromab will be administered at low doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the low dose of ponsegromab or placebo. In optional Cohort D, ponsegromab will be administered at high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the high dose of ponsegromab or placebo. In a separate open-label, PK cohort (Cohort B), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 4 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab. There is no placebo in the open-label, PK cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 - Clinical Summary Score (CSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed health related quality of life (HRQL) in participants with heart failure (HF) over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ total symptom score (TSS): mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in KCCQ-23 CSS at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status. |
| Change From Baseline in KCCQ-23-Overall Summary Score (OSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status. |
| Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status. |
| Change From Baseline in KCCQ-23-TSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status. |
| Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status. |
| Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status. |
| Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23-CSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 CSS Score at Week 22: Cohort A | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status. |
| Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A | Week 22 | KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status. |
| Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | The 6-minute walk test (6MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWD (distance travelled in meters) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise. |
| Change From Baseline in 6MWD at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWD (distance travelled in meters) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise. |
| Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Version 7a) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo | Baseline [the last measurement on study Day 1], Week 22 | The PROMIS Fatigue 7a is a self-reported measure that assessed a range of symptoms in the past 7 days from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. The short form (SF) 7A consisted of 7 items that study participants rated from 1: "Never" to 5: "Always". A global raw score ranged from 7 to 35 was calculated and translated into a T-score with minimum of 29.4 and maximum of 83.2 (mean = 50, a standard deviation \[SD\] = 10) using the applicable score conversion provided in the PROMIS user's manual. Higher scores indicated more fatigue. |
| Change From Baseline in PROMIS Fatigue (Version 7a) at Week 22: Cohort A | Baseline [the last measurement on study Day 1], Week 22 | The PROMIS Fatigue 7a is a self-reported measure that assessed a range of symptoms in the past 7 days from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. The short form (SF) 7A consisted of 7 items that study participants rated from 1: "Never" to 5: "Always". A global raw score ranged from 7 to 35 was calculated and translated into a T-score (mean = 50, a standard deviation \[SD\] = 10) using the applicable score conversion provided in the PROMIS user's manual. Higher scores indicated more fatigue. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs): Cohort A | From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks) | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. TESAE was a TEAE which met the definition of serious adverse event (SAE) viz. any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was considered an important medical event. AEs included SAEs and all other AEs (non-SAEs). |
| Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort A | From first dose of study treatment (Day 1) up to Week 22 | Laboratory parameters included were: hematology (hemoglobin, hematocrit, red blood cells \[RBC\] count, platelet count, white blood cells \[WBC\] count) and chemistry (urea and creatinine, estimated glomerular filtration rate \[eGFR\], cystatin C \[at baseline only\], sodium, potassium, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, alkaline phosphatase \[ALP\], total protein, glucose \[non-fasting\] and lipid panel, total cholesterol, high-density lipoprotein \[HDL\] cholesterol, Non HDL cholesterol, calculated low-density lipoprotein \[LDL\] cholesterol and triglycerides. Number of participants with any abnormalities in laboratory test parameters as judged by investigator were reported. |
| Number of Participants With Abnormalities in Vital Signs: Cohort A | From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks) | Vital signs abnormalities criteria included: supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg), increase and decrease in change of \>= 30mmHg; supine diastolic blood pressure (DBP) \<50 mmHg, increase and decrease in change of \>=20mmHg; and pulse rate (PR) \<40 beats per minute (bpm) and \>120 bpm. |
| Number of Participants With TEAEs and TEASAEs: Cohort B | From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 12 (maximum up to approximately 22 weeks) | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. TESAE was a TEAE which met the definition of SAE viz. any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was considered an important medical event. AEs included SAEs and all other AEs (non-SAEs). |
| Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort B | From first dose of study treatment (Day 1) maximum up to 4 weeks post Week 12 (maximum up to approximately 16 weeks) | Laboratory parameters included were: hematology (hemoglobin, hematocrit, RBC count, platelet count, WBC count) and chemistry (urea and creatinine, eGFR, cystatin C \[at baseline only\], sodium, potassium, AST, ALT, total bilirubin, ALP, total protein, glucose \[non-fasting\] and lipid panel, total cholesterol, HDL cholesterol, Non HDL cholesterol, calculated LDL cholesterol and triglycerides. Number of participants with any abnormalities in laboratory test parameters as judged by investigator were reported. |
| Number of Participants With Abnormalities in Vital Signs: Cohort B | From start of study drug on Day 1 maximum up to 4weeks post last dose on Week 12 (maximum up to approximately Week 16) | Vital signs criteria included: supine SBP \<90 mmHg, increase and decrease in change of \>= 30mmHg; supine DBP \<50 mmHg, increase and decrease in change of \>=20mmHg; and PR \<40 bpm to \>120 bpm. |
Countries
Australia, Canada, China, Czechia, Germany, Hungary, Japan, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
A total of 455 participants were enrolled, randomized and treated in this study: 433 participants in cohort A and 22 participants in cohort B.
Pre-assignment details
The following cohorts were planned for the study: Cohort A, Cohort B, Cohort C and Cohort D. No participants were enrolled either in Cohort C or Cohort D due to study termination and data for these cohorts is not reported in any section of the record.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 55-64 years | 57 Participants |
| Age, Customized 65-74 years | 146 Participants |
| Age, Customized 75-84 years | 177 Participants |
| Age, Customized Less than (<) 55 years | 16 Participants |
| Age, Customized More than or equal to (>=) 85 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 43 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 328 Participants |
| Sex: Female, Male Female | 110 Participants |
| Sex: Female, Male Male | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 17 / 198 | 2 / 21 | 1 / 17 | 13 / 197 | 0 / 5 | 0 / 9 | 1 / 8 |
| other Total, other adverse events | 94 / 198 | 15 / 21 | 11 / 17 | 102 / 197 | 2 / 5 | 3 / 9 | 6 / 8 |
| serious Total, serious adverse events | 55 / 198 | 7 / 21 | 7 / 17 | 69 / 197 | 0 / 5 | 1 / 9 | 2 / 8 |
Outcome results
None listed