A PHASE 1/2, MULTI-CENTER, OPEN-LABEL, SINGLE- AND MULTIPLE-DOSEESCALATION, DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND PRELIMINARY EFFICACY OF PF-08154225, IN PARTICIPANTS WITH AUTOIMMUNE DISEASES INCLUDING ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), OR RHEUMATOID ARTHRITIS (RA), OR IDIOPATHIC INFLAMMATORY MYOSITIS (IIM) OR SYSTEMIC SCLEROSIS (SSC)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- Pfizer
- 入组人数
- 54
- 主要终点
- Incidence and severity of Treatment Emergent Adverse Event (AE) including protocol specified adverse event of special interest(AESI)
研究概览
简要总结
The purpose of this study is to learn about the safety and effects of the study medication called PF-08154225 for the potential treatment of autoimmune diseases. An autoimmune disease is a condition that makes a person's immune system attack its healthy cells by mistake. This study is particularly looking at autoimmune diseases called as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Idiopathic Inflammatory Myositis (IIM) or Systemic Sclerosis (SSc).
This study is divided into 3 parts: Part 1a, Part 1b and Part 2. Parts 1a and 1b are seeking participants with Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis and Part 2 with also Idiopathic Inflammatory Myositis (IIM) or Systemic Sclerosis (SSc).
Participants can take part only in one part of the study.
All participants in this study will receive PF-08154225 at the study clinic. In Part 1a participants will receive single administration of PF-08154225 after which they will be observed at the study clinic during regular visits through week 16 or longer.
In Part 1b the participants will receive multiple administration of PF-08154225 after which they will be monitored in similar a manner as in Part 1a through week 24 or longer.
In Part 2 participants will receive multiple administrations of PF-08154225. After the last injection they will be monitored for safety through week 52 or longer.
详细描述
This clinical trial consists of Part I and Part II. Phase I consists of dose escalation. The main goal of dose escalation is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-08154225 in participants with Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA), and the main goal of Part II is to assess effects of PF-08154225 on the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy in participants with SLE or RA or IIM or SSc.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Select Inclusion Criteria
- •At age between 18 and 70 years at Screening.
- •Confirmed diagnosis of RA according to the 2010 American College of Rheumatology (ACR)/ European Alliance of Associations for Rheumatology (EULAR) criteria at Screening, with symptom at least 6 months prior to Screening
- •Clinical diagnosis of SLE according to the 1997 ACR Criteria for the Classification of SLE Or confirmed diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria at Screening, with symptom at least 6 months prior to Screening.
- •Clinical diagnosis of 1 of the 3 IIM subtypes based on phenotype, and/or prior muscle biopsy, and positive myositis-specific autoantibody (MSA) / myositis-associated antibody (MMA)
- •Classification of SSc according to the 2013 ACR/EULAR criteria at Screening
排除标准
- •Any medical or psychiatric condition, including active suicidal ideation or any laboratory abnormality, that increases study risk or makes the participant unsuitable.
- •Active central nervous system (CNS) co-morbidity
- •Any complications of disease under study that in the judgement of the investigator may be life or organ threatening or require prohibited medication
- •Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection
- •Active or recent clinically significant infections
- •Chronic or active Hepatitis B and C
- •Past or current therapies with T-cell engager (TCEs), bone marrow cell transplant, stem cell transplant, chimeric antigen receptor T-cell (CAR-T) cell therapy.
- •For SLE, no catastrophic or severe antiphospholipid syndrome (APS), severe unstable neuropsychiatric SLE.
- •Felty's syndrome, juvenile arthritis or idiopathic arthritis before age of 16
- •SSc renal crisis within 6 months prior to screening, UIP pattern if entering on interstitial lung disease interstitial lung disease (ILD) criteria
- •Diagnosis of Inclusion body myositis (IBM) and Usual interstitial pneumonia (UIP) pattern if entering on ILD criteria
研究组 & 干预措施
several cohorts with the target doses
Single and multiple dose cohorts. Part 1: Participants will receive different target doses of PF-08154225 in a single and multiple dose escalation stage to evaluate their safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD). Part 2: Participants will receive different doses of PF-08154225 in an open label single arm setting to evaluate their safety, tolerability, PK, PD and preliminary efficacy.
干预措施: PF-08154225 (Drug)
结局指标
主要结局
Incidence and severity of Treatment Emergent Adverse Event (AE) including protocol specified adverse event of special interest(AESI)
时间窗: From first dose through End of Study (up to Week 16 in Part 1a, Week 24 in Part 1b and Week 52 in Part2)
An AE is defined as any untoward medical event that occurs after a participant receives the investigational drug, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the investigational drug.
Dose Limiting Toxicity (DLT)
时间窗: During the DLT observation period (up to 22 days after the last dose)
Frequencies of abnormal safety laboratory tests, vital signs, ECGs.
时间窗: From first dose of study intervention through End of Study (up to Week 16 in Part 1a, Week 24 in Part 1b and Week 52 in Part 2)
次要结局
- Number of Participants With Disease Flare(Up to Week 52)
- Change From Baseline in Disease Activity Score 28 Using C-Reactive Protein (DAS28-CRP)(Baseline, Week 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI)(Baseline, Week 52)
- Participants Achieving American College of Rheumatology (ACR) Response Criteria(Up to Week 52)
- Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Score(Baseline, Week 52)
- Change From Baseline in Manual Muscle Testing-8 (MMT-8) Score(Baseline, Week 52)
- Change From Baseline in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS)(Baseline, Week 52)
- Circulating B-Cell Counts(From first dose of study intervention through End of Study (Week 16 for Part 1a, week 24 for Part 1b and Week 52 for Part 2 or longer if extension of the follow up was needed)
- Participants With Anti-Drug Antibodies (ADAs) Against PF-08154225(From first dose of study intervention through End of Study (Week 16 for Part 1a, Week 24 for Part 1b and Week 52 for Part2)
- Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score(Baseline, Week 52)
- Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Score(Baseline, Week 52)
- Change From Baseline in Tender Joint Count(Baseline, Week 52)
- Change From Baseline in Swollen Joint Count(Baseline, Week 52)
- Change From Baseline in Physician Global Assessment Score(Baseline, Week 52)
- Number of Participants With DORIS Remission(Up to Week 52)
- Number of Participants With Lupus Low Disease Activity State (LLDAS)(Up to Week 52)
- Number of Participants With SLE Responder Index-4 (SRI-4) Response(Up to Week 52)
- Maximum Observed Serum Concentration (Cmax) of PF-08154225(From first dose through the last pharmacokinetic assessment (up to Week 16 in Part 1a and up to Week 24 in Part 1b))
- Time to Maximum Observed Serum Concentration (Tmax) of PF-08154225(From first dose through the last pharmacokinetic assessment (up to Week 16 in Part 1a and up to Week 24 in Part 1b))
- Area Under the Serum Concentration-Time Curve (AUC) of PF-08154225(From first dose through the last pharmacokinetic assessment (up to Week 16 in Part 1a and up to Week 24 in Part 1b))
- Change From Baseline in Modified Rodnan Skin Score (mRSS) in Participants With Systemic Sclerosis(Baseline, Week 52)
- Participants Achieving Composite Response Index in Systemic Sclerosis (CRISS) Response(Up to Week 52)