A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO -CONTROLLED, FIRST-IN-HUMAN TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF 06755347 AFTER SINGLE ASCENDING INTRAVENOUS AND SUBCUTANEOUS DOSING IN HEALTHY ADULT MALE PARTICIPANTS AND OPEN-LABEL AFTER SINGLE SUBCUTANEOUS DOSING IN MALE AND FEMALE PARTICIPANTS WITH PERSISTENT OR CHRONIC PRIMARY IMMUNE THROMBOCYTOPENIA
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 58
- 试验地点
- 6
- 主要终点
- Number of Participants With Vital Signs Meeting Categorical Criteria
研究概览
简要总结
This phase 1 single ascending dose study will provide a first in human assessment of safety and tolerability of PF-06755347 in healthy adult males as well as adult males and females with Immune Thrombocytopenia (ITP). Pharmacokinetics and pharmacodynamics will also be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind (investigator and subject), sponsor open in healthy male participants. Masking will not be applied for participants with ITP (all ITP participants will receive PF-06755347).
入排标准
- 年龄范围
- 18 Years 至 55 Years（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
PF-06755347 intravenous healthy participant
intravenous administration
干预措施: PF-06755347 intravenous healthy participant (Drug)
Placebo intravenous healthy participant
intravenous administration
干预措施: Placebo intravenous healthy participant (Drug)
PF-06755347 subcutaneous healthy participant
subcutaneous administration
干预措施: PF-06755347 subcutaneous healthy participant (Drug)
Placebo subcutaneous healthy participant
subcutaneous administration
干预措施: Placebo subcutaneous healthy participant (Drug)
PF-06755347 subcutaneous ITP
subcutaneous
干预措施: PF-06755347 subcutaneous ITP (Drug)
结局指标
主要结局
Number of Participants With Vital Signs Meeting Categorical Criteria
时间窗: Baseline, Study Days 1, 2, 4, 6, 8, 11, 15, 22, 29 and 36 for IV treatment cohorts, and Baseline, Study Days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and 71 for SC treatment cohorts.
Supine blood pressure and pulse rate were measured. Categorical classes for vital signs of potential clinical concerns were defined as followed: systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); diastolic blood pressure (DBP) \<50 mmHg; pulse rate \<40 beats per minute (bpm); pulse rate \>120 bpm, and increase from baseline in SBP ≥30 mmHg; decrease from baseline in SBP ≥30 mmHg; increase from baseline in DBP ≥20 mmHg; decrease from baseline in DBP ≥20 mmHg. Baseline was defined as the mean of the replicated predose (0 hour) measurement on Day 1.
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs
时间窗: Baseline (Study Day -2) through study completion (Study Day 36 for IV treatment cohorts, and Study Day 71 SC treatment cohorts).
Adverse event (AE) was any untoward medical occurrence in the participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious AE was any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was considered to be an important medical event. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent. AEs included both serious and non-serious AEs.
Number of Participants With Laboratory Test Abnormalities
时间窗: Baseline, Study Days 1, 2, 4, 6, 8, 11, 15, 22, 29 and 36 for IV treatment cohorts, and Baseline, Study Days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and 71 for SC treatment cohorts.
Laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute and percent total neutrophils, eosinophils, monocytes, basophils and lymphocytes),chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin and total protein),urinalysis(pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy, urinary albumin to creatinine ratio and urinary protein to creatinine ratio) and other tests. Abnormality was determined by the investigator. Only lab abnormalities with at least 1 occurrence in participants are reported.
Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria
时间窗: Baseline (Study Day 1, predose), Study Days 1 (postdose), 2, 4, 6, 8, 11, 22, 36 (end of study visit for IV treatment cohorts) and 71 (end of study visit for SC treatment cohorts).
Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. Baseline was defined as the average of the triplicate predose recordings collected at 0 hour on Day 1.
次要结局
- Maximum Plasma Concentration (Cmax) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- Cmax of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Cmax(dn) of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Tmax of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- AUClast of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Area Under the Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- Area Under the Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- AUClast(dn) of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Dose Normalized Cmax (Cmax(dn)) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- Time for Cmax (Tmax) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- Dose Normalized AUClast (AUClast(dn)) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- AUCinf of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Dose Normalized AUCinf (AUCinf(dn)) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- AUCinf(dn) of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Terminal Half-life (t½) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- t½ of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Clearance (CL) of PF-06755347 Following Single IV Dose(Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.)
- Apparent Clearance (CL/F) of PF-06755347 Following Single SC Dose(Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.)
- Number of Participants With Positive Anti-Drug Antibody to PF-06755347(Baseline, Study Days 8, 15, and 36 for all treatment cohorts plus Day 71 for SC treatment cohorts)
- Change From Baseline in Interferon Gamma (IFN-γ ) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)
- Change From Baseline in Tumor Necrosis Factor Alpha (TNFα) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)
- Change From Baseline in Interleukin 6 (IL-6) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)
- Change From Baseline in Complement 3a (C3a) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)
- Change From Baseline in Complement 5a (C5a) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)
- Change From Baseline in Activated Factor B (Bb) at Scheduled Timepoints(Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.)