A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment

• Register: ClinicalTrials.gov
• Last refreshed on: 17 March 2025
• Main ID: NCT05133531
• Date of registration: 12/11/2021
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals
• Public title: A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment ACCESS-1
• Scientific title: A Randomized, Open-Label, C5 Inhibitor-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy
• Date of first enrolment: August 1, 2022
• Target sample size: 190
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05133531
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, China, Colombia, Greece, Hungary, India, Italy, Japan, Jordan, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Poland, Romania, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Miao Chen

• Name: Clinical Trials Administrator

• Name: Clinical Trial Management
• Affiliation: Regeneron Pharmaceuticals

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH
granulocytes or monocytes as described in the protocol

2. Active disease, as defined by the presence of 1 or more PNH-related signs or
symptoms as described in the protocol

3. LDH level =2 × ULN at the screening visit

4. Willing and able to comply with clinic/remote visits and study-related procedures,
including completion of the full series of meningococcal vaccinations required per
protocol

Key Exclusion Criteria:

1. Prior treatment with eculizumab within 3 months prior to screening, ravulizumab
within 6 months prior to screening, or other complement inhibitors within 5
half-lives of the respective agent prior to screening

2. Receipt of an organ transplant, history of bone marrow transplantation or other
hematologic transplant

3. Body weight <40 kilograms at screening visit

4. Planned use of any complement inhibitor therapy other than study drugs during the
treatment period

5. Not meeting meningococcal vaccination requirements and, at a minimum documentation
of quadrivalent meningococcal vaccination within 5 years prior to the screening
visit and serotype B vaccine within 3 years prior to the screening visit as
described in the protocol.

6. Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes
ACWY and B).

7. Unable to take antibiotics for meningococcal prophylaxis (if required by local
ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where
available, or national guidelines/local practice, or if necessary when
administration of the first dose of the vaccination is less than 2 weeks prior to
study treatment initiation)

8. Any active, ongoing infection or a recent infection requiring ongoing systemic
treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening
or during the screening period

9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria

Intervention(s)

Drug: Pozelimab

Drug: Ravulizumab

Drug: Cemdisiran

Drug: Eculizumab

Primary Outcome(s)

Maintenance of adequate control of hemolysis [Time Frame: From week 8 through week 26, inclusive]

Percent change in lactate dehydrogenase (LDH) [Time Frame: From baseline to week 26]

Transfusion avoidance [Time Frame: From post-baseline day 1 through week 26]

Secondary Outcome(s)

Adequate control of hemolysis [Time Frame: From week 8 through week 26, inclusive]

Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30 [Time Frame: From baseline to week 26]

Change in hemoglobin levels [Time Frame: From baseline to week 26]

Concentrations of total pozelimab in serum [Time Frame: Up to 60 weeks]

Hemoglobin stabilization [Time Frame: From day 1 (post-baseline) through week 26]

Number of units of RBC transfused [Time Frame: Post-baseline Day 1 through week 26]

Rate of RBC transfused [Time Frame: Post-baseline Day 1 through week 26]

Breakthrough hemolysis [Time Frame: From post-baseline day 1 through week 26]

Incidence and severity of TEAEs leading to treatment discontinuation [Time Frame: Up to 26 weeks]

Percent change in LDH [Time Frame: From baseline to week 26]

Concentration of total C5 in plasma [Time Frame: Up to 60 weeks]

Concentrations of total ravulizumab in serum [Time Frame: Up to 34 weeks]

Maintenance of adequate control of hemolysis [Time Frame: From week 8 through week 26, inclusive]

Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) [Time Frame: Change from baseline to week 26]

Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab [Time Frame: Up to 60 weeks]

Normalization of LDH [Time Frame: Between week 8 through week 26, inclusive]

Change in total CH50 [Time Frame: From baseline to week 26]

Incidence of treatment emergent ADAs to cemdisiran [Time Frame: Up to 60 weeks]

Transfusion avoidance [Time Frame: Day 1 through week 26]

Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [Time Frame: From baseline to week 26]

Concentrations of cemdisiran in plasma [Time Frame: Up to 60 weeks]

Incidence and severity of treatment emergent serious adverse events (SAEs) [Time Frame: Up to 26 weeks]

Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest [Time Frame: Up to 26 weeks]

Percentage of days with LDH =1.5 × ULN [Time Frame: Between week 8 and week 26, inclusive]

Time to first LDH =1.5 × ULN [Time Frame: Up to Week 26]

Concentrations of total eculizumab in serum [Time Frame: Up to 30 weeks]

Percent change in total CH50 [Time Frame: From baseline to week 26]

Time to first LDH =1.0 × ULN [Time Frame: Up to Week 26]

Secondary ID(s)

2023-509657-31-00

R3918-PNH-2021

2020-004486-40

Source(s) of Monetary Support

Please refer to primary and secondary sponsors