Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
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)
Interventions
DRUGPozelimab
Administered per the protocol
DRUGCemdisiran
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Patients Entering from the Parent Study 1. 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. 2. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol. Patients Entering with C5 polymorphism 1. 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 2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes 3. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol 4. LDH level ≥2 × 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 Key
Exclusion criteria
Patients Entering from the Parent Study 1. 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 2. 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 1. 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 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. 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 4. Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening 5. Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol 6. Known hereditary complement deficiency 7. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases 8. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent serious adverse events (SAEs) | 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 |
| Severity of treatment-emergent SAEs | Up to week 108 | — |
| Incidence of treatment emergent adverse events of special interest (AESIs) | 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 |
| Severity of treatment emergent AESIs | Up to week 108 | — |
| Incidence of adverse events (AEs) leading to permanent treatment discontinuation | 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 adverse events (AEs) leading to permanent treatment discontinuation | 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. |
| Percent change from baseline in lactate dehydrogenase (LDH) | Baseline to week 36 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adequate control of hemolysis (LDH ≤1.5 × ULN) | Post-baseline through week 108 | — |
| Transfusion avoidance | Post-baseline through week 36 | Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values |
| 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 | — |
| Hemoglobin stabilization | Post-baseline through week 36 | Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL |
| Percent change in LDH | From baseline to week 48 | — |
| Change in fatigue | From baseline to week 36 | Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. |
| Change in physical function (PF) scores on the EORTC QLQ-C30 | From baseline to week 36 | EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire) EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change. |
| Change in PF scores on the EORTC QLQ-C30 | From baseline to week 48 | EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire) EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change. |
| Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30 | From baseline to week 36 | GHS/QoL (Global Health Status/ Quality of Life) Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change. |
| Normalization of LDH | From post-baseline through week 108 | — |
| Rate of red blood cell (RBC) transfusion | Post-baseline through week 36 | Per protocol algorithm |
| Rate of RBC transfusion | Post-baseline through week 48 | Per protocol algorithm |
| Number of units of RBC transfusion | Post-baseline through week 36 | Per protocol algorithm |
| Percentage of days with LDH ≤1.5x upper limit of normal (ULN) | Post-baseline through week 36 | — |
| Percentage of days with LDH ≤1.5x ULN | Post-baseline through week 48 | — |
| Change in hemoglobin levels | From baseline to week 36 | — |
| 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 | — |
Countries
Canada, Colombia, Hungary, India, Italy, Japan, Jordan, Malaysia, Peru, Philippines, Poland, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed