Trial Outcomes & Findings for A Study to Learn How the Study Medicine (Ponsegromab) is Changed and Eliminated From Healthy Chinese Adults (NCT NCT05685264)
NCT ID: NCT05685264
Last Updated: 2024-10-01
Results Overview
AUCinf was defined as area under the serum concentration-time profile from time 0 extrapolated to infinite time.
COMPLETED
PHASE1
18 participants
Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
2024-10-01
Participant Flow
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.
Participant milestones
| Measure |
Cohort 1: Ponsegromab 100 mg
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single subcutaneous (SC) dose of ponsegromab 100 mg on Day 1.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Learn How the Study Medicine (Ponsegromab) is Changed and Eliminated From Healthy Chinese Adults
Baseline characteristics by cohort
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.0 Years
n=5 Participants
|
25.0 Years
n=7 Participants
|
30.0 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum pharmacokinetic (PK) parameters of interest calculated.
AUCinf was defined as area under the serum concentration-time profile from time 0 extrapolated to infinite time.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
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
|
590200 nanogram (ng)*day/milliliter (mL)
Geometric Coefficient of Variation 59
|
|
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
|
1105000 nanogram (ng)*day/milliliter (mL)
Geometric Coefficient of Variation 44
|
PRIMARY outcome
Timeframe: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.
AUClast was defined as area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
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
|
647700 ng*day/mL
Geometric Coefficient of Variation 60
|
|
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
|
1036000 ng*day/mL
Geometric Coefficient of Variation 42
|
PRIMARY outcome
Timeframe: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.
Cmax was defined as maximum observed concentration. Cmax was observed directly from data.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab
Unbound ponsegromab
|
4698 ng/mL
Geometric Coefficient of Variation 41
|
21330 ng/mL
Geometric Coefficient of Variation 64
|
|
Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab
Total ponsegromab
|
6978 ng/mL
Geometric Coefficient of Variation 28
|
24910 ng/mL
Geometric Coefficient of Variation 60
|
PRIMARY outcome
Timeframe: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.
Tmax was defined as time for Cmax. Tmax was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Time for Cmax (Tmax) of Unbound and Total Ponsegromab
Unbound ponsegromab
|
7.01 day
Interval 5.0 to 14.0
|
5.00 day
Interval 3.0 to 14.0
|
|
Time for Cmax (Tmax) of Unbound and Total Ponsegromab
Total ponsegromab
|
7.01 day
Interval 3.0 to 14.0
|
6.99 day
Interval 3.0 to 28.0
|
PRIMARY outcome
Timeframe: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127Population: All enrolled participants who received a dose of ponsegromab and who had at least 1 of the serum PK parameters of interest calculated.
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.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Terminal Half Life (t1/2) of Unbound and Total Ponsegromab
Unbound ponsegromab
|
8.393 day
Standard Deviation 2.8461
|
10.37 day
Standard Deviation 3.7287
|
|
Terminal Half Life (t1/2) of Unbound and Total Ponsegromab
Total ponsegromab
|
23.40 day
Standard Deviation 3.8135
|
31.09 day
Standard Deviation 8.9457
|
SECONDARY outcome
Timeframe: From the first dose of study intervention on Day 1 to Day 127Population: All enrolled participants who received a dose of ponsegromab.
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.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
4 Participants
|
7 Participants
|
|
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study intervention on Day 1 to Day 127Population: All enrolled participants who received a dose of ponsegromab.
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.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Number of Participants With Treatment-Related TEAEs and SAEs
TEAEs
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Related TEAEs and SAEs
SAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study intervention on Day 1 to Day 127Population: All enrolled participants who received a dose of ponsegromab.
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.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Urate (mg/dL) >1.2 x ULN
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Leukocyte Esterase ≥1
|
2 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Ery. Mean Corpuscular HGB Concentration (g/dL) >1.1 x upper limit of normal (ULN)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Mean Platelet Volume (fL) <0.9 x lower limit of normal (LLN)
|
4 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Lymphocytes (10^3/mm^3) >1.2 x ULN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Neutrophils (10^9/L) <0.8 x LLN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Alanine Aminotransferase (U/L) >3.0 x ULN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
pH (Scalar) <1.0 x LLN
|
6 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Ketones ≥1
|
1 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Urine Hemoglobin ≥1
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Urobilinogen ≥1
|
0 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Urine Leukocytes (/uL) >1.0 x ULN
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Epithelial Cells ≥6
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study intervention on Day 1 to Day 127Population: All enrolled participants who received a dose of ponsegromab.
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.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change in Vital Signs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study intervention on Day 1 to Day 127Population: All enrolled participants who received a dose of ponsegromab.
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%.
Outcome measures
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 Participants
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 Participants
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG)
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1: Ponsegromab 100 mg
Cohort 2: Ponsegromab 400 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: Ponsegromab 100 mg
n=9 participants at risk
Participants in Cohort 1 (ponsegromab 100 mg cohort) received a single SC dose of ponsegromab 100 mg on Day 1.
|
Cohort 2: Ponsegromab 400 mg
n=9 participants at risk
Participants in Cohort 2 (ponsegromab 400 mg cohort) received a single SC dose of ponsegromab 400 mg on Day 1.
|
|---|---|---|
|
Cardiac disorders
Atrioventricular block first degree
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Infections and infestations
COVID-19
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
22.2%
2/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Infections and infestations
Gingivitis
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
33.3%
3/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Injury, poisoning and procedural complications
Animal bite
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
22.2%
2/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Blood uric acid increased
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Blood glucose increased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Blood creatinine increased
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Urine ketone body present
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Urine leukocyte esterase positive
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
22.2%
2/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
Urobilinogen urine increased
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Investigations
White blood cells urine positive
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
|
Skin and subcutaneous tissue disorders
Mechanical urticaria
|
0.00%
0/9 • From the first dose of study intervention on Day 1 to Day 127
|
11.1%
1/9 • From the first dose of study intervention on Day 1 to Day 127
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER