Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 3
- 主要终点
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
研究概览
简要总结
This is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for evaluation.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years old (inclusive)
- •Diagnosed with PNH (white blood cell (WBC) clone >10%)
- •Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
- •Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) < LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study
- •Last transfusion within 12 months prior to screening
- •Platelet count of >30,000/mm3 at the screening visit
- •Absolute neutrophil count >500/ mm3 at the screening visit
- •Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study
- •Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
- •Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with pegcetacoplan. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
- •Willing and able to give informed consent
排除标准
- •Prior eculizumab (Soliris®) treatment
- •Active bacterial infection
- •Hereditary complement deficiency
- •History of bone marrow transplantation
- •Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin
- •Participation in any other investigational drug trial or exposure to another investigational agent, device or procedure within 30 days
- •Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening
- •Breast-feeding women
- •History of meningococcal disease
研究组 & 干预措施
Experimental: Cohort 1
270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364*
干预措施: Pegcetacoplan (Drug)
结局指标
主要结局
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
时间窗: From Day 1 to 30 days after the last dose (approximately 56 weeks)
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (v4.03) based on: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening, Grade 5: Death related to AE.
Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level
时间窗: Baseline and Day 365
Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Change From Baseline in Haptoglobin Level
时间窗: Baseline and Day 365
Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Change From Baseline in Hemoglobin (Hb) Level
时间窗: Baseline and Day 365
Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
次要结局
- Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level(Baseline and Day 365)
- Mean Number of Red Blood Cell (RBC) Transfusions Per Month(From Day 1 to Day 364)
- Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL(Baseline and Day 365)
- Mean Serum Concentrations of Pegcetacoplan(Day 365)
- Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)(Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.)
- Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score(Baseline and Day 365)
- Mean Change From Baseline in Total Bilirubin Level(Baseline and Day 365)
- Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)(Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.)