A PHASE 1 FIRST IN HUMAN, RANDOMIZED, DOUBLE BLIND, SPONSOR OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF 07242813 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH ATOPIC DERMATITIS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 121
- 试验地点
- 7
- 主要终点
- Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
研究概览
简要总结
This is the first time PF-07242813 will be given to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07242813 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Single ascending doses of PF-07242813 or placebo in healthy participants
Participants will receive a single intravenous dose of either PF-07242813 or placebo
干预措施: PF-07242813 (Drug)
Single ascending doses of PF-07242813 or placebo in healthy participants
Participants will receive a single intravenous dose of either PF-07242813 or placebo
干预措施: Placebo (Drug)
Multiple ascending doses of PF-07242813 or placebo in healthy participants
Participants will receive multiple subcutaneous doses PF-07242813 or placebo
干预措施: PF-07242813 (Drug)
Multiple ascending doses of PF-07242813 or placebo in healthy participants
Participants will receive multiple subcutaneous doses PF-07242813 or placebo
干预措施: Placebo (Drug)
Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis
Participants will receive a single intravenous dose of either PF-07242813 or placebo
干预措施: PF-07242813 (Drug)
Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis
Participants will receive a single intravenous dose of either PF-07242813 or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
时间窗: From start of study treatment on Day 1 to Day 99
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From start of study treatment on Day 1 to Day 71
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 SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs
时间窗: From start of study treatment on Day 1 to Day 99
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 SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
时间窗: From initiation of treatment to day 71
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities
时间窗: Baseline (last pre-dose measurement) to Day 99
Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Part 2: Number of Participants With TEAEs and TESAEs
时间窗: From start of study treatment on Day 1 to Week 16
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 SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Part 2: Number of Participants With Clinically Significant Findings in Vital Signs
时间窗: From start of study treatment on Day 1 to Week 16
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities
时间窗: Baseline (last pre-dose measurement) to Day 71
Pre-defined criteria for laboratory parameters were hemoglobin (HGB) (\<0.8\* Lower limit normal (LLN)), Erythrocyte (Ery). Mean Corpuscular (MC) Volume (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* Upper limit normal (ULN)), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Part 2: Number of Participants With Laboratory Test Abnormalities
时间窗: Baseline (last pre-dose measurement) to Week 16
Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities
时间窗: From pre-dose up to 6 hours post dose on Day 1
Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG)
时间窗: From pre-dose on Day 1 up to Day 71
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG
时间窗: From pre-dose on Day 1 up to Day 99
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
Part 2: Number of Participants With Clinically Significant Findings in ECG
时间窗: From pre-dose on week 1 to week 16
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
次要结局
- Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813(Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV)
- Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813(Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV)
- Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813(Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV)
- Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813(Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV)
- Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6(Baseline, Week 6)
- Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813(Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose))
- Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813(Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV)
- Part 1: MAD Cohorts: Cmax for PF-07242813(Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose))
- Part 1: MAD Cohorts: Tmax for PF-07242813(Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose))
- Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813(Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose))