A Study to Learn How the Study Medicine (Ponsegromab) is Changed and Eliminated From Healthy Chinese Adults

A PHASE 1, OPEN-LABEL, SINGLE DOSE STUDY TO INVESTIGATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF PONSEGROMAB ADMINISTERED SUBCUTANEOUSLY IN HEALTHY ADULT CHINESE PARTICIPANTS

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05685264

Enrollment

Registered

2023-01-17

Start date

2023-01-18

Completion date

2023-07-07

Last updated

2024-10-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Ponsegromab, Healthy Volunteers

Brief summary

The purpose of this clinical trial is to learn about the safety of the study medicine (ponsegromab) and how it undergoes change and elimination in healthy Chinese adults. This study is seeking male and female Chinese participants who are very healthy as confirmed after some medical tests. All participants in this study will receive Ponsegromab only once: * for half of the participants, ponsegromab will be given as a shot in the front of the thigh, abdomen, or outer area of the upper arm at the study clinic. * for another half of the participants, ponsegromab will be given as four shots in the front of the thigh, abdomen, or outer area of the upper arm at the study clinic. We will measure the amount of the study medicine in the blood of the participants after giving the shots. Later we will examine experiences of people receiving the study medicine. This will help us understand how the medicine is changed and eliminated from your body and to decide if the study medicine is safe. Participants will take part in this study for 22 weeks. During this time, they will stay at the study clinic for the first 8 days and will visit the study clinic about 8 times.

Interventions

DRUGPonsegromab

Participants will receive one subcutaneous injection

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

1. Participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent 2. Male and female Chinese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, BP and PR measurement, 12-lead ECG, and laboratory tests. Chinese participants are defined as individuals currently residing in mainland China who were born in China and have both parents of Chinese descent. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 4. BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb). 5. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Document..

Exclusion criteria

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 2. History of HIV infection, syphilis, hepatitis B, or hepatitis C; positive testing for HIV, syphilis, HBsAg, or HCVAb. Hepatitis B vaccination is allowed. 3. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or molecules made of components of monoclonal antibodies. 4. History of recurrent infections or active infection within 28 days of screening. 5. History of sensitivity to heparin or heparin-induced thrombocytopenia. 6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 7. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention. 8. Exposure to live vaccines within 28 days of screening. 9. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or marketed or investigational monoclonal antibodies within 3 months or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). 10. A positive urine drug test. 11. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. 12. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval \>450 msec, or QRS interval \>120 msec). If the baseline uncorrected QT interval is \>450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant. 13. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: * AST or ALT level ≥1.5 × ULN; * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN. 14. COVID-19 positive. 15. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 240 mL beer, 30 mL of 40% spirit or 90 mL of wine). 16. Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing. 17. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. 18. 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.

Design outcomes

Primary

Measure	Time frame	Description
Terminal Half Life (t1/2) of Unbound and Total Ponsegromab	Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127	t1/2 was defined as terminal half life. t1/2 was calculated as Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab	Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127	AUCinf was defined as area under the serum concentration-time profile from time 0 extrapolated to infinite time.
Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab	Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127	AUClast was defined as area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration.
Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab	Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127	Cmax was defined as maximum observed concentration. Cmax was observed directly from data.
Time for Cmax (Tmax) of Unbound and Total Ponsegromab	Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127	Tmax was defined as time for Cmax. Tmax was observed directly from data as time of first occurrence.

Secondary

Measure	Time frame	Description
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From the first dose of study intervention on Day 1 to Day 127	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. TEAEs were defined as events that started on or after the first dose but before the end of the study (approximately 18 weeks post dose on Day 1). An SAE was defined as 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.
Number of Participants With Treatment-Related TEAEs and SAEs	From the first dose of study intervention on Day 1 to Day 127	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. TEAEs were defined as events that started on or after the first dose but before the end of the study (approximately 18 weeks post dose on Day 1). An SAE was defined as 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. Causality of the TEAEs and SAEs was judged by the investigator.
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	From the first dose of study intervention on Day 1 to Day 127	Hematology parameters included hemoglobin, hematocrit, red blood cell, white blood cell and platelet count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean platelet volume, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and creatinine. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Only those categories in which at least 1 participant had data were reported.
Number of Participants With Clinically Significant Change in Vital Signs	From the first dose of study intervention on Day 1 to Day 127	Vital sign measurements included supine blood pressure and pulse rate. Any safety assessments (vital sign measurements) including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the investigator or were considered meeting the AE definition and are listed below.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG)	From the first dose of study intervention on Day 1 to Day 127	ECG abnormalities criteria included: 1) maximum QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>30, \>60; 2) maximum pulse rate (msec): ≥300, baseline \>200 and maximum increase ≥25%, baseline ≤200 and maximum increase ≥50%; 3) maximum QRS (msec): ≥140, increase ≥50%.

Countries

China

Participant flow

Pre-assignment details

A total of 18 participants were screened and assigned to receive the study intervention. All of them received ponsegromab. All 18 participants completed treatment and follow-up phases.

Participants by arm

Arm	Count
Cohort 1: Ponsegromab 100 mg Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.	9
Cohort 2: Ponsegromab 400 mg Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.	9
Total	18

Baseline characteristics

Characteristic	Cohort 2: Ponsegromab 400 mg	Total	Cohort 1: Ponsegromab 100 mg
Age, Continuous	25.0 Years	30.0 Years	34.0 Years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	9 Participants	18 Participants	9 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	1 Participants	4 Participants	3 Participants
Sex: Female, Male Male	8 Participants	14 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 9
other Total, other adverse events	4 / 9	7 / 9
serious Total, serious adverse events	0 / 9	0 / 9

Outcome results

Primary

Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab

AUCinf was defined as area under the serum concentration-time profile from time 0 extrapolated to infinite time.

Time frame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127

Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum pharmacokinetic (PK) parameters of interest calculated.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Ponsegromab 100 mg	Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab	Unbound ponsegromab	109000 nanogram (ng)*day/milliliter (mL)	Geometric Coefficient of Variation 58
Cohort 1: Ponsegromab 100 mg	Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab	Total ponsegromab	350300 nanogram (ng)*day/milliliter (mL)	Geometric Coefficient of Variation 21
Cohort 2: Ponsegromab 400 mg	Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab	Unbound ponsegromab	590200 nanogram (ng)*day/milliliter (mL)	Geometric Coefficient of Variation 59
Cohort 2: Ponsegromab 400 mg	Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab	Total ponsegromab	1105000 nanogram (ng)*day/milliliter (mL)	Geometric Coefficient of Variation 44

Primary

Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab

AUClast was defined as area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration.

Time frame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127

Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Ponsegromab 100 mg	Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab	Unbound ponsegromab	95170 ng*day/mL	Geometric Coefficient of Variation 55
Cohort 1: Ponsegromab 100 mg	Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab	Total ponsegromab	337800 ng*day/mL	Geometric Coefficient of Variation 20
Cohort 2: Ponsegromab 400 mg	Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab	Unbound ponsegromab	647700 ng*day/mL	Geometric Coefficient of Variation 60
Cohort 2: Ponsegromab 400 mg	Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab	Total ponsegromab	1036000 ng*day/mL	Geometric Coefficient of Variation 42

Primary

Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab

Cmax was defined as maximum observed concentration. Cmax was observed directly from data.

Time frame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127

Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Ponsegromab 100 mg	Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab	Unbound ponsegromab	4698 ng/mL	Geometric Coefficient of Variation 41
Cohort 1: Ponsegromab 100 mg	Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab	Total ponsegromab	6978 ng/mL	Geometric Coefficient of Variation 28
Cohort 2: Ponsegromab 400 mg	Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab	Unbound ponsegromab	21330 ng/mL	Geometric Coefficient of Variation 64
Cohort 2: Ponsegromab 400 mg	Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab	Total ponsegromab	24910 ng/mL	Geometric Coefficient of Variation 60

Primary

Terminal Half Life (t1/2) of Unbound and Total Ponsegromab

t1/2 was defined as terminal half life. t1/2 was calculated as Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.

Time frame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127

Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: Ponsegromab 100 mg	Terminal Half Life (t1/2) of Unbound and Total Ponsegromab	Unbound ponsegromab	8.393 day	Standard Deviation 2.8461
Cohort 1: Ponsegromab 100 mg	Terminal Half Life (t1/2) of Unbound and Total Ponsegromab	Total ponsegromab	23.40 day	Standard Deviation 3.8135
Cohort 2: Ponsegromab 400 mg	Terminal Half Life (t1/2) of Unbound and Total Ponsegromab	Unbound ponsegromab	10.37 day	Standard Deviation 3.7287
Cohort 2: Ponsegromab 400 mg	Terminal Half Life (t1/2) of Unbound and Total Ponsegromab	Total ponsegromab	31.09 day	Standard Deviation 8.9457

Primary

Time for Cmax (Tmax) of Unbound and Total Ponsegromab

Tmax was defined as time for Cmax. Tmax was observed directly from data as time of first occurrence.

Time frame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127

Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.

Arm	Measure	Group	Value (MEDIAN)
Cohort 1: Ponsegromab 100 mg	Time for Cmax (Tmax) of Unbound and Total Ponsegromab	Unbound ponsegromab	7.01 day
Cohort 1: Ponsegromab 100 mg	Time for Cmax (Tmax) of Unbound and Total Ponsegromab	Total ponsegromab	7.01 day
Cohort 2: Ponsegromab 400 mg	Time for Cmax (Tmax) of Unbound and Total Ponsegromab	Unbound ponsegromab	5.00 day
Cohort 2: Ponsegromab 400 mg	Time for Cmax (Tmax) of Unbound and Total Ponsegromab	Total ponsegromab	6.99 day

Secondary

Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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. TEAEs were defined as events that started on or after the first dose but before the end of the study (approximately 18 weeks post dose on Day 1). An SAE was defined as 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.