Clinical trial NCT05685264: A Study to Learn How the Study Medicine (Ponsegromab) is Changed and Eliminated From Healthy Chinese Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Ponsegromab
Healthy Volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-01-17
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Unbound and Total Ponsegromab
timeFrame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
measure: Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Unbound and Total Ponsegromab
timeFrame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
measure: Maximum Observed Serum Concentration (Cmax) of Unbound and Total Ponsegromab
timeFrame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
measure: Time for Cmax (Tmax) of Unbound and Total Ponsegromab
timeFrame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
measure: Terminal Half Life (t1/2) of Unbound and Total Ponsegromab
timeFrame: Pre-dose, 12, 24, 48, 72, 120, 168 hours after dose on Day 1, Days 10, 15, 29, 50, 71, 93, 106, and 127
Secondary outcomes:
measure: Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study intervention on Day 1 to Day 127
measure: Number of Participants With Treatment-Related TEAEs and SAEs
timeFrame: From the first dose of study intervention on Day 1 to Day 127
measure: Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
timeFrame: From the first dose of study intervention on Day 1 to Day 127
measure: Number of Participants With Clinically Significant Change in Vital Signs
timeFrame: From the first dose of study intervention on Day 1 to Day 127
measure: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG)
timeFrame: From the first dose of study intervention on Day 1 to Day 127
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: HuaShan Hospital
state: Shanghai
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: