An Open-Label, Single Arm Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor-Naive or Have Not Recently Received Complement Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis
研究概览
简要总结
The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment-naive to complement inhibitor therapy or have not recently received complement inhibitor therapy.
The secondary objectives of the study are:
- To evaluate the safety and tolerability of REGN3918.
- To evaluate the effect of REGN3918 on parameters of intravascular hemolysis
- To assess the concentrations of total REGN3918 in serum.
- To evaluate the incidence of treatment-emergent anti-drug antibodies to REGN3918 over time
- To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue and health-related quality of life
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high-sensitivity flow cytometry
- •PNH granulocytes > 10% at screening visit
- •Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms (eg, fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], history of a MAVE [including thrombosis], dysphagia, or erectile dysfunction) or history of red blood cell (RBC) transfusion due to PNH within 3 months of screening.
- •Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening visit.
排除标准
- •Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C)
- •History of bone marrow transplantation
- •Body weight < 40 kilograms at screening visit
- •Peripheral blood absolute neutrophil count (ANC) <500/μL [<0.5 x 109/L] or peripheral blood platelet count <50,000/μL
- •Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of active or latent tuberculosis infection (LTBI) during screening period
- •Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic prophylaxis therapy as recommended in the study
- •Any active, ongoing infection within 2 weeks of screening or during the screening period
- •Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, or patients with short life expectancy
- •Women who are pregnant, breastfeeding, or who have a positive pregnancy test at screening visit or day 1
- •NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
REGN3918
Cohort A (Dose Confirmation) If a decision is made to expand Cohort A, patients will be assigned to Cohort A.
Cohort B (Dose Expansion) If a decision is made to progress to Cohort B, patients will be assigned to Cohort B.
干预措施: REGN3918 (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis
时间窗: Week 4 through Week 26
Participants were considered to have had adequate control of intravascular hemolysis if all of their lactose dehydrogenase (LDH) readings from Week 4 through Week 26 inclusive had values less than or equal to ≤ 1.5 × upper limit of normal (ULN). Participants must have greater than or equal to (≥) 50 percent (%) of scheduled LDH measures in those weeks, must not have had more than (\>) 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. Participants were considered not to have had adequate control of intravascular hemolysis if they failed any of these criteria.
Percentage of Participants Who Achieved Transfusion Avoidance
时间窗: Up to 26 Weeks
Transfusion avoidance was defined as not having received red blood cell (RBC) transfusion during the first 26 weeks. A transfusion was counted only if it was per-protocol, that is, it followed the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level \< 9 grams per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level \< 7 g/dL (without anemia symptoms).
次要结局
- Percentage of Participants Who Had Breakthrough Hemolysis (BTH)(Baseline up to 26 Weeks)
- Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis(Week 4 through Week 26)
- Time to First Lactate Dehydrogenase (LDH) ≤1.5 x ULN(Up to Week 26)
- Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26(Week 4 through Week 26)
- Rate of Transfusion With Red Blood Cells (RBCs)(Baseline up to Week 26)
- Change From Baseline in LDH Levels at Week 26(Baseline, Week 26)
- Percent Change From Baseline in LDH Levels at Week 26(Baseline, Week 26)
- Number of Units of Transfusion With RBCs(Baseline up to Week 26)
- Change From Baseline in RBC Hemoglobin Levels at Week 26(Baseline, Week 26)
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) at Week 26(Baseline, Week 26)
- Change From Baseline in European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Index Score(Baseline, Week 26)
- Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Week 26(Baseline, Week 26)
- Change From Baseline in Free Hemoglobin Levels at Week 26(Baseline, Week 26)
- Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) at Week 26(Baseline, Week 26)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 26(Baseline, Week 26)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs(Baseline up to Week 26)
- Number of Participants With TEAEs Based on Severity(Baseline up to Week 26)
- Percent Change From Baseline in CH50 up to Week 26(Baseline up to Week 26)
- Serum Concentrations of Total REGN3918(Pre-dose (Day 0), End of infusion at Days 0, 2, 7, 28, 56, 84, 112, 140, and 182)
- Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters(Baseline up to Week 26)
- Number of Participants With Clinically Meaningful Changes in Vital Signs(Baseline up to Week 26)
- Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) Response to REGN3918(Baseline up to Week 26)
- Number of Participants With Clinically Meaningful Changes in 12-lead Electrocardiograms (ECGs)(Baseline up to Week 26)