A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 44
- 主要终点
- Number of Patients Achieving a Response (R) at Week 24
研究概览
简要总结
The purpose of the study is to determine the efficacy of pegcetacoplan administration compared to placebo in increasing hemoglobin (Hgb) level from baseline and avoiding transfusion in participants with primary cold agglutinin disease (CAD).
详细描述
This is a blind (actual treatment not disclosed to Investigator or participant) study to study pegcetacoplan in people with cold agglutinin disease. The study will consist of a 4-week screening period where selected tests will be conducted to ensure that the patient is eligible to participate in the study, followed by Part A, a 24-week blinded treatment period where the participants will receive either pegcetacoplan or a placebo treatment, looking like pegcetacoplan but with no effect. After this period, the participants will move into Part B, a 24-week period where they will all receive pegcetacoplan. Part C is a 48-week maintenance period with pegcetacoplan for all participants. After the end of treatment participants will undergo a safety follow visit about 8 weeks after last dose.
All eligible study participants will receive pegcetacoplan or placebo treatment, administered via subcutaneous infusion twice a week at home. The subcutaneous infusion requires two small needles to be inserted into the fatty layer of tissue under the skin and the investigational medication will flow into the body. Study participants and/or caregivers will be trained on home administration of pegcetacoplan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •Diagnosis of primary CAD.
- •Hb level ≤ 9 g/dL.
- •Documented results from bone marrow biopsy within 1 year of screening
- •Either have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (Types A, C, W, Y, and B), and Haemophilus influenzae (Type B) within 2 years prior to screening or agree to receive vaccination during screening.
- •Women of childbearing potential (WOCBP), defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last investigational medicinal product (IMP) dose.
- •Men must agree to the following for the duration of the study and 8 weeks after their last IMP dose:
- •Avoid fathering a child.
- •Use protocol-defined methods of contraception.
- •Refrain from donating sperm.
- •Willing and able to give written informed consent.
排除标准
- •Have received other anti-complement therapies (approved or investigational) within 5 half-lives of the agent prior to randomization.
- •Treatment with rituximab monotherapy within 12 weeks prior to randomization, or rituximab combination therapies (e.g., with bendamustine, fludarabine, other cytotoxic drugs or ibrutinib) within 16 weeks prior to randomization.
- •Diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies.
- •History of an aggressive lymphoma or presence of a lymphoma requiring therapy.
- •Have received an organ transplant.
- •Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection.
- •Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN), or direct bilirubin levels > 2 x ULN.
- •Inability to cooperate with study procedures.
研究组 & 干预措施
Pegcetacoplan Double Blind During Part A
1080 mg, subcutaneous injection, twice weekly
干预措施: Pegcetacoplan (Drug)
Placebo Matching Pegcetacoplan-Double-blind During Part A
Sodium acetate, subcutaneous injection, twice weekly
干预措施: Placebo matching Pegcetacoplan (Drug)
Open-label Pegcetacoplan During Parts B and C
1080 mg, subcutaneous injection, twice weekly
干预措施: Pegcetacoplan (Drug)
Open-label Pegcetacoplan (Placebo Matching Pegcetacoplan During Part A) During Parts B&C
Sodium acetate, subcutaneous injection, twice weekly
干预措施: Placebo matching Pegcetacoplan (Drug)
结局指标
主要结局
Number of Patients Achieving a Response (R) at Week 24
时间窗: Week 24
A participant was considered to have a response if the Hgb level increased greater than or equal to (\>=) 1.5 gram per deciliter (g/dL) from baseline and this increase was maintained from Week 16 through Week 24 in absence of blood transfusion from Week 5 through Week 24.
次要结局
- Change From Baseline to Week 24 in Hemoglobin (Hgb) Level-Part A in the Absence of Intercurrent Events (ICEs).(Week 24)
- Number of Patients Achieving Transfusion Avoidance From Week 5 to Week 24-Part A(Week 24)
- Change From Baseline to Week 24 in FACT-An Scale Score (Quality of Life)-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Number of Packed Red Blood Cell Transfusions Received by Patients From Week 5 to Week 24-Part A(Week 24)
- Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for ARC Levels-Part A(Week 24)
- Change From Baseline to Week 24 in LDH Levels-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 24 in Haptoglobin Levels-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 24 in Indirect Bilirubin-Part A in the Absence of Intercurrent Events (ICE)(Week 24)
- Change From Baseline to Week 24 in ARC-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 24 in D-dimer Levels-Part A in the Absence of Intercurrent Events (ICEs(Week 24)
- Normalization of Markers of Hemolysis (LDH) at Week 24-Part A(Week 24)
- Normalization of Markers of Hemolysis (Indirect Bilirubin) at Week 24-Part A(Week 24)
- Normalization of Markers of Hemolysis (ARC) at Week 24-Part A(Week 24)
- Normalization of Markers of Hemolysis (Haptoglobin) at Week 24-Part A(Week 24)
- Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Haptoglobin Levels-Part A(Week 24)
- Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Hemoglobin Levels-Part A(Week 24)
- Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for LDH Levels-Part A(Week 24)
- Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Indirect Bilirubin Levels-Part A(Week 24)
- Number of Packed Red Blood Cell Units Transfused From Week 5 to Week 24-Part A(Week 5 to Week 24)
- Change From Baseline to Week 24 in FACIT-F Subscale Score-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 24 in SF-12-Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs)(Week 24)
- Change From Baseline to Week 48 in Hemoglobin (Hgb) Level-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in LDH Level-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in Haptoglobin Level-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in Indirect Bilirubin Level-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in ARC-Part B in the Absence of Intercurrent Events (ICEs)(Week 48)
- Change From Baseline to Week 48 in D-dimer Levels-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in FACT-An Scale Score (Quality of Life)-Part B in the Absence of Intercurrent Events (ICEs)(Week 48)
- Change From Baseline to Week 48 in FACIT-F Subscale Score-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)
- Change From Baseline to Week 48 in SF-12-Part B in the Absence of Intercurrent Events (ICEs).(Week 48)