A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED EVALUATION OF SINGLE DOSES OF PF-07209326 IN HEALTHY PARTICIPANTS (SAFETY, TOLERABILITY, AND PHARMACOKINETICS [PK]) FOLLOWED BY AN OPEN LABEL, REPEAT DOSE EVALUATION IN SICKLE CELL DISEASE PARTICIPANTS (SAFETY, TOLERABILITY, PK AND EFFICACY)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 52
- 试验地点
- 27
- 主要终点
- Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
研究概览
简要总结
This Phase 1 first-in-human, first-in-patient, single ascending dose and multiple dose study will be a randomized, double-blind, placebo-controlled investigation of the safety, tolerability, and pharmacokinetics of PF-07209326 in healthy participants and participants with sickle cell disease.
详细描述
Part 1 will evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of PF-07209326 delivered by subcutaneous injection or intravenous delivery in healthy volunteer participants. After establishing the safety and tolerability in healthy participants, Part 2 will evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of subcutaneously delivered multiple dose of PF-07209326 in participants with sickle cell disease.
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)
盲法说明
Masking will only be applicable to Part 1 of the study where Healthy participants will be enrolled and randomized to receive either PF-07209326 or to placebo. In Part 2 of the study, all eligible SCD participants will receive PF-07209326 and no masking will be required.
入排标准
- 年龄范围
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Health Participants:
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
排除标准
- •Healthy Participants:
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, immunocompromised (or known disorder of the immune system), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
- •History of active or latent tuberculosis (TB) regardless of treatment or positive QuantiFeron TB test.
- •Participants with any of the following acute or chronic infections or infection history:
- •Any infection requiring treatment within 2 weeks prior to the screening visit.
- •Any infection requiring hospitalization, parenteral antimicrobial therapy within 30 days of the first dose of investigational product.
- •Any infection judged to be an opportunistic infection, within the past 6 months of the first dose of the investigational product.
- •Known active or history of frequent bacterial, viral, fungal, mycobacterial or other infections as determined by the PI.
- •Participants with a fever within the last 7 days prior to dosing.
- •Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.
- •Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- •Inclusion Criteria for SCD Participants
- •Participants between the ages of 16 and 70 years old with a confirmed diagnosis of stable sickle cell disease (HbSS or HBS β0 thalassemia).
- •Medical history of ≥2 and ≤ 10 medical utilization VOCs in 12 months prior to screening.
- •≥75% of daily ePRO diary completion, over a minimum of 14 days during the screening period.
- •Fully vaccinated for COVID-19 in accordance with the Center for Disease Control guidance prior to Screening or must be negative for SARS-CoV-2 by polymerase chain reaction (PCR) within 72 hours of the Day 1 visit.
- •Body Mass Index (BMI) ≤34.9 kg/m2 and weight ≥50 kg.
- •Exclusion Criteria for SCD Participants
- •Evidence of ongoing uncontrolled clinically significant co-morbidity (e.g. intercurrent events that result in signs symptoms that have an adverse impact on the respective individual's usual function) hematological (non-SCD), renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including stroke within 2 years prior to screening), hepatic, psychiatric or neurological.
- •Evidence or history of cardiac disease includes myocardial infarction, clinically significant cardiac arrhythmia (eg, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia), left ventricular failure, unstable angina, and coronary artery bypass grafting.
- •History of cancer (other than cutaneous basal cell or carcinoma in-situ) in the previous 5 years.
- •Active infection with Hepatitis B or C or HIV. Individuals seropositive for infection with Hepatitis C must be negative for viral RNA by PCR on at least 2 determinations.
- •History of active or latent tuberculosis (TB) regardless of treatment or positive QuantiFeron TB test.
- •Major surgery <3 months prior to baseline or planned significant medical procedures during the study.
- •Participants with any of the following acute or chronic infections or infection history:
- •Any infection requiring systemic treatment within 2 weeks prior to the screening visit.
- •Any infection requiring hospitalization, parenteral antimicrobial therapy within 30 days of the first dose of investigational product.
- •Any infection judged to be an opportunistic infection, within the past 6 months of the first dose of the investigational product.
- •Known active or history of frequent viral, fungal or other infections as determined by the Investigator.
- •Participants with a fever within the last 7 days prior to dosing.
- •Evidence or history of clinically significant orthostatic blood pressure changes.
- •Other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- •Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.
- •Administration of voxelotor within 4 weeks prior to screening or planned use during the study.
- •Administration of crizanlizumab within 12 weeks prior to screening or planned use during the study.
- •Planned transfusion during the study.
结局指标
主要结局
Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
时间窗: Day 1 up to Day 85 (SAD) or Day 113 (MD)
Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
Number of subjects with change from baseline in vital signs
时间窗: Day 1 up to Day 85 (SAD) or Day 85 (MD)
blood pressure, pulse rate, temperature, respiration rate
Number of subjects with change from baseline in electrocardiogram (ECG) parameters
时间窗: Day 1 up to Day 85 (SAD) or Day 85 (MD)
Number of subjects with change from baseline in electrocardiogram (ECG) parameters
Percentage of subjects with infusion site reactions
时间窗: Day 1 up to Day 11 post each dose (SD)
Percentage of subjects with infusion site reactions
Percentage of subjects with injection site reactions
时间窗: Day 1 up to Day 11 post (SAD) Day 1 up to Day 85 (MD)
Percentage of subjects with injection site reactions
Percentage of subjects with laboratory abnormalities
时间窗: Day 1 up to Day 85 (SAD) or Day 113 (MD)
Percentage of subjects with laboratory abnormalities
次要结局
- SAD: Single Dose PK / CL/F (SC only)(Day 1 up to Day 85)
- SAD: Single Dose PK / DN Cmax(Day 1 up to Day 85)
- SAD: Single Dose PK / AUCinf(Day 1 up to Day 85)
- SAD: Single Dose PK / Vz/F (SC only)(Day 1 up to Day 85)
- SAD: Single Dose PK / AUClast(Day 1 up to Day 85)
- SAD: Single Dose PK / DN AUClast(Day 1 up to Day 85)
- SAD: Single Dose PK / DN AUCinf(Day 1 up to Day 85)
- MD: AUCtau(Day 1 up to Day 22)
- SAD: Single Dose PK /Cmax(Day 1 up to Day 85)
- SAD: Single Dose PK / Tmax(Day 1 up to Day 85)
- MD:ADA and/or NAb(Day 1 up to Day 113)
- SAD: Single Dose PK / t½(Day 1 up to Day 85)
- SAD: Single Dose PK / CL (IV only)(Day 1 up to Day 85)
- SAD: Single Dose PK / Vss (IV only)(Day 1 up to Day 85)
- SAD: Single Dose PK / F (SC only)(Day 1 up to Day 85)
- SAD:ADA and/or NAb(Day 1 up to Day 85)
- Patient-reported VOC event rate and VOC day rate(Day 1 to 85)