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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 (ACCESS-EXT)

A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works. (ACCESS-EXT)

Taneja Deepak

Regeneron Pharmaceuticals, Inc.

777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

clinicaltrials@regeneron.com

Rosario Chikako

Parexel International Inc.

Kayabacho Tower Building, 1-21-2, Shinkawa, Chuo-ku, Tokyo

+81-80-8929-3137

Clinicaltrial-registration@parexel.com

Recruiting

Mar. 02, 2024

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

parallel assignment

treatment purpose

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 x 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
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. 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 Exclusion Criteria apply.

Both

Paroxysmal Nocturnal Hemoglobinuria

Pozelimab and Cemdisiran Combination:
Drug: Pozelimab
SC Q4W
Other names: REGN3918

Drug: Cemdisiran
SC Q4W
Other names: ALN-CC5

Administered SC per the protocol
The duration of the OLEP for a patient is approximately 108 weeks, excluding screening.

- Incidence of treatment-emergent serious adverse events (SAEs)
- Severity of treatment-emergent SAEs
- Incidence of treatment emergent adverse events of special interest (AESIs)
- Severity of treatment emergent AESIs
- Incidence of adverse events (AEs) leading to permanent treatment discontinuation
- Severity of adverse events (AEs) leading to permanent treatment discontinuation
- Percent change from baseline in lactate dehydrogenase (LDH)

- Maintenance of adequate control of hemolysis (LDH <=1.5 x ULN)
- Adequate control of hemolysis (LDH <=1.5 x ULN) at each visit
- Transfusion avoidance
- Breakthrough hemolysis (defined as LDH >=2 x ULN [subsequent to initial achievement of LDH <=1.5 x ULN] concomitant with signs or symptoms associated with hemolysis)
- Hemoglobin stabilization
- Percent change in LDH
- Change in fatigue
- Change in physical function (PF) scores on the EORTC QLQ-C30
- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
- Normalization of LDH
- Rate of red blood cell (RBC) transfusion
- Number of units of RBC transfusion
- Percentage of days with LDH <=1.5 x upper limit of normal (ULN)
- Change in hemoglobin levels
- Change in total complement hemolytic activity assay (CH50)
- Percent change in CH50
- Concentrations of total pozelimab in serum
- Concentrations of cemdisiran in plasma
- Incidence of treatment-emergent anti-drug antibodies to pozelimab
- Incidence of treatment-emergent anti-drug antibodies to cemdisiran
- Concentration of total complement component 5 (C5) in plasma
- Percent change of concentration of total C5 in plasma

+81-3-3448-6111

Sept. 12, 2023

Yes

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

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