An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 202
- 试验地点
- 67
- 主要终点
- Incidence of treatment-emergent serious adverse events (SAEs)
研究概览
简要总结
This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as "study drugs" in this section.
This study is looking at several other research questions, including:
- How effective is the pozelimab + cemdisiran combination?
- What side effects may happen from taking the study drugs?
- How much of each study drug is in the blood at different times?
- Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patients Entering from the Parent Study
- •Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021[NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
- •Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
- •Patients Entering with C5 polymorphism
- •Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
- •Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
- •Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
- •LDH level ≥2 × upper limit of normal (ULN) at the screening visit
- •Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
排除标准
- •Patients Entering from the Parent Study
- •Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
- •Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study
- •Patients Entering with C5 polymorphism
- •Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
- •Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- •Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol
- •Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
- •Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
- •Known hereditary complement deficiency
- •Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
- •Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol
- •Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
PNH Transition Patients
Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531])
干预措施: Cemdisiran (Drug)
PNH Transition Patients
Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531])
干预措施: Pozelimab (Drug)
C5 Polymorphism Patients
Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1.
干预措施: Pozelimab (Drug)
C5 Polymorphism Patients
Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1.
干预措施: Cemdisiran (Drug)
结局指标
主要结局
Incidence of treatment-emergent serious adverse events (SAEs)
时间窗: Up to week 108
An SAE is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect. * Is an important medical event
Percent change from baseline in lactate dehydrogenase (LDH)
时间窗: Baseline to week 36
Severity of adverse events (AEs) leading to permanent treatment discontinuation
时间窗: Up to week 108
Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.
Severity of treatment emergent AESIs
时间窗: Up to week 108
Incidence of adverse events (AEs) leading to permanent treatment discontinuation
时间窗: Up to week 108
Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.
Severity of treatment-emergent SAEs
时间窗: Up to week 108
Incidence of treatment emergent adverse events of special interest (AESIs)
时间窗: Up to week 108
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it
次要结局
- Percentage of days with LDH ≤1.5x ULN(Post-baseline through week 108)
- Change in hemoglobin levels(From baseline to week 108)
- Normalization of LDH(From post-baseline through week 108)
- Rate of red blood cell (RBC) transfusion(Post-baseline through week 36)
- Rate of RBC transfusion(Post-baseline through week 108)
- Number of units of RBC transfusion(Post-baseline through week 108)
- Percentage of days with LDH ≤1.5x upper limit of normal (ULN)(Post-baseline through week 36)
- Adequate control of hemolysis (LDH ≤1.5 × ULN)(Post-baseline through week 108)
- Transfusion avoidance(Post-baseline through week 108)
- Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)(Post-baseline through week 108)
- Hemoglobin stabilization(Post-baseline through week 108)
- Percent change in LDH(From baseline to week 108)
- Change in fatigue(From baseline to weeks 108)
- Change in physical function (PF) scores on the EORTC QLQ-C30(From baseline to week 36)
- Change in PF scores on the EORTC QLQ-C30(From baseline to week 108)
- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30(From baseline to week 108)
- Change in total complement hemolytic activity assay (CH50)(Through week 108)
- Percent change in CH50(Through week 108)
- Concentrations of total pozelimab in serum(Through week 108)
- Concentrations of cemdisiran in plasma(Through week 24)
- Incidence of treatment-emergent anti-drug antibodies to pozelimab(Through week 108)
- Incidence of treatment-emergent anti-drug antibodies to cemdisiran(Through week 108)
- Concentration of total complement component 5 (C5) in plasma(Through week 108)
- Percent change of concentration of total C5 in plasma(Through week 108)
- Transfusion avoidance(Post-baseline through week 36)
- Transfusion avoidance(Post-baseline through week 48)
- Transfusion avoidance(Post-baseline through week 76)
- Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)(Post-baseline through week 36)
- Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)(Post-baseline through week 48)
- Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)(Post-baseline through week 76)
- Hemoglobin stabilization(Post-baseline through week 36)
- Hemoglobin stabilization(Post-baseline through week 48)
- Hemoglobin stabilization(Post-baseline through week 76)
- Percent change in LDH(From baseline to week 48)
- Percent change in LDH(From baseline to week 76)
- Change in fatigue(From baseline to week 36)
- Change in fatigue(From baseline to week 48)
- Change in fatigue(From baseline to week 76)
- Change in PF scores on the EORTC QLQ-C30(From baseline to week 48)
- Change in PF scores on the EORTC QLQ-C30(From baseline to week 76)
- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30(From baseline to week 36)
- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30(From baseline to week 48)
- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30(From baseline to week 76)
- Rate of RBC transfusion(Post-baseline through week 48)
- Rate of RBC transfusion(Post-baseline through week 76)
- Number of units of RBC transfusion(Post-baseline through week 36)
- Number of units of RBC transfusion(Post-baseline through week 48)
- Number of units of RBC transfusion(Post-baseline through week 76)
- Percentage of days with LDH ≤1.5x ULN(Post-baseline through week 48)
- Percentage of days with LDH ≤1.5x ULN(Post-baseline through week 76)
- Change in hemoglobin levels(From baseline to week 36)
- Change in hemoglobin levels(From baseline to week 48)
- Change in hemoglobin levels(From baseline to week 76)