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
- 尚未招募
- 入组人数
- 202
- 试验地点
- 8
- 主要终点
- (1) 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?
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What side effects may happen from taking the study drugs?
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How much of each study drug is in your blood at different times?
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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
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •(A) 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.
- •(B) 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 more than equals to 2 IN TO upper limit of normal (ULN) at the screening visit 5.Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
排除标准
- •(A) 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 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 (B) 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 OR Exclusion Criteria apply.
结局指标
主要结局
(1) Incidence of treatment-emergent serious adverse events (SAEs)
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(2) Severity of treatment-emergent SAEs
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(3) Incidence of treatment emergent adverse events of special interest (AESIs)
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(4) Severity of treatment emergent AESIs
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(5) Incidence of adverse events (AEs) leading to permanent treatment discontinuation
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(6) Severity of adverse events (AEs) leading to permanent treatment discontinuation
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
(7) Percent change from baseline in lactate dehydrogenase (LDH)
时间窗: (1) Up to week 108 | (2) Up to week 108 | (3) Up to week 108 | (4) Up to week 108 | (5) Up to week 108 | (6) Up to week 108 | (7) Baseline to week 36
次要结局
- Adequate control of hemolysis (LDH less than or equal to 1.5 IN TO ULN)(Post-baseline through week 108)
- Transfusion avoidance, defined as not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values(Post-baseline through week 36,)
- Breakthrough hemolysis (defined as LDH greater than or equal to 2 IN TO ULN [subsequent to initial achievement of LDH less than or equal to 1.5 IN TO ULN] concomitant with signs or symptoms associated with hemolysis)(Post-baseline through week 36, 48, 76 and 108)
- Hemoglobin stabilization- Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per of greater than or equal to 2 g per dL(Post-baseline through week 36, 48, 76 and 108)
- Percent change in LDH(From baseline to weeks 48, 76, and 108)
- Change in fatigue as measured by the FACIT-Fatigue scale(From baseline to weeks)
- Change in physical function (PF) scores on the EORTC QLQ-C30(From baseline to weeks 36, 48, 76 and 108)
- Change in GHS OR quality of life scale on the EORTC QLQ C30(From baseline to weeks 36, 48, 76, and 108)
- Normalization of LDH(From post-baseline through week 108)
- Rate of red blood cell (RBC) transfusion
- Number of units of RBC transfusion(Postbaseline)
- Percentage of days with LDH less than or equal to 1.5 IN TO upper limit of normal(Post-baseline through Weeks 36, 48, 76, and 108)
- Change in hemoglobin levels(From baseline to weeks 36, 48, 76, and 108)
- Change in total complement hemolytic activity assay(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)