A study to examine the long-term safety, tolerability, and effectiveness of Pozelimab and Cemdisiran combination therapy in adult patients with Paroxysmal Nocturnal Hemoglobinuria
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Registration Number
- JPRN-jRCT2031230013
- Lead Sponsor
- Aurand Lisa
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 11
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.
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 x upper limit of normal (ULN) at the screening visit
Note: Other protocol-defined Inclusion Criteria apply.
Patients Entering from the Parent Study
1. Significant protocol deviation(s) in the parent study based on the investigators 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. No documentation of meningococcal vaccination within 5 years prior to enrollment
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 Exclusion Criteria apply.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Incidence of treatment-emergent serious adverse events (SAEs) [Time Frame: Up to week 108]<br>- Severity of treatment-emergent SAEs [Time Frame: Up to week 108]<br>- Incidence of treatment emergent adverse events of special interest (AESIs) [Time Frame: Up to week 108]<br>- Severity of treatment emergent AESIs [Time Frame: Up to week 108]<br>- Incidence of adverse events (AEs) leading to permanent treatment discontinuation [Time Frame: Up to week 108]<br>- Severity of adverse events (AEs) leading to permanent treatment discontinuation [Time Frame: Up to week 108]<br>- Percent change from baseline in lactate dehydrogenase (LDH) [Time Frame: Baseline to week 36]
- Secondary Outcome Measures
Name Time Method