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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

5 May 2023 → ongoing

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2023-510336-36-00

EudraCT number

2021-004931-10

ClinicalTrials.gov

NCT05744921

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to describe the long-term safety, tolerability, and efficacy of pozelimab + cemdisiran combination therapy in patients with PNH.

Secondary objectives 1

1. The secondary objectives of the study are to describe the long-term effect of the combination of pozelimab + cemdisiran on: • Measures of intravascular hemolysis • Transfusion parameters • Hemoglobin levels • Fatigue as assessed by a Patient Reported Outcome (PRO) • Physical Function (PF) as assessed by a PRO • Change in Global Health Status (GHS) as assessed by a PRO • Complement activation • Concentrations of total pozelimab in serum and cemdisiran and total C5 protein in plasma • Immunogenicity of pozelimab and cemdisiran

Conditions and MedDRA coding

Paroxysmal nocturnal hemoglobinuria (PNH)

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Patients Entering from the Parent Study: Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
3. 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
4. Patients Entering with C5 polymorphism: Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
5. Patients Entering with C5 polymorphism: Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
6. Patients Entering with C5 polymorphism: LDH level ≥2 × upper limit of normal (ULN) at the screening visit
7. Patients Entering with C5 polymorphism: Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol

Exclusion criteria 10

1. 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 safety of the patient
2. Patients Entering from the Parent Study: 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
3. 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
4. Patients Entering with C5 polymorphism: Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
5. Patients Entering with C5 polymorphism: 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
6. Patients Entering with C5 polymorphism: Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
7. Patients Entering with C5 polymorphism: Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
8. Patients Entering with C5 polymorphism: Known hereditary complement deficiency
9. Patients Entering with C5 polymorphism: Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
10. Patients Entering with C5 polymorphism: 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/ Exclusion Criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Incidence of treatment-emergent serious adverse events (SAEs)
2. Severity of treatment-emergent SAEs
3. Incidence of treatment emergent adverse events of special interest (AESIs)
4. Severity of treatment emergent AESIs
5. Incidence of adverse events (AEs) leading to permanent treatment discontinuation
6. Severity of adverse events (AEs) leading to permanent treatment discontinuation
7. Percent change from baseline in lactate dehydrogenase (LDH)

Secondary endpoints 21

1. Adequate control of hemolysis (LDH ≤1.5 × ULN)
2. Transfusion avoidance
3. Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
4. Hemoglobin stabilization
5. Percent change in LDH
6. Change in fatigue
7. Change in physical function (PF) scores on the EORTC QLQ-C30
8. Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
9. Normalization of LDH
10. Rate of red blood cell (RBC) transfusion
11. Number of units of RBC transfusion
12. Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
13. Change in hemoglobin levels
14. Change in total complement hemolytic activity assay (CH50)
15. Percent change in CH50
16. Concentrations of total pozelimab in serum
17. Concentrations of cemdisiran in plasma
18. Incidence of treatment-emergent anti-drug antibodies to pozelimab
19. Incidence of treatment-emergent anti-drug antibodies to cemdisiran
20. Concentration of total complement component 5 (C5) in plasma
21. Percent change of concentration of total C5 in plasma

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 12

Locations

6 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications