Clinical trial • Phase III • Haematology
CEMDISIRAN for Paroxysmal nocturnal hemoglobinuria
Phase III trial of CEMDISIRAN for Paroxysmal nocturnal hemoglobinuria. open-label, none/not specified-controlled. 185 participants.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Paroxysmal nocturnal hemoglobinuria
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Oligonucleotide
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 29-10-2024
- First CTIS Authorization Date
- 27-11-2024
Trial design
open-label, none/not specified-controlled Phase III trial in Italy, Hungary, Poland and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Target Sample Size
- 185
Eligibility
Recruits 185 The trial record flags vulnerable population selection (isVulnerablePopulationSelected = true). The public documentation and submitted materials include subject information and informed consent forms (multiple country/language versions) and recruitment/informed consent procedure documents. Consent is obtained from adult participants using subject information and informed consent forms provided in country-specific languages (and English versions where provided); no pediatric assent procedures are indicated in the public materials..
- Vulnerable Population
- The trial record flags vulnerable population selection (isVulnerablePopulationSelected = true). The public documentation and submitted materials include subject information and informed consent forms (multiple country/language versions) and recruitment/informed consent procedure documents. Consent is obtained from adult participants using subject information and informed consent forms provided in country-specific languages (and English versions where provided); no pediatric assent procedures are indicated in the public materials.
Inclusion criteria
- {"criterion_text":"- 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.\n- Patients Entering from the Parent Study: Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol\n- 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\n- Patients Entering with C5 polymorphism: Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes\n- 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\n- Patients Entering with C5 polymorphism: LDH level ≥2 × upper limit of normal (ULN) at the screening visit\n- 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
- {"criterion_text":"- 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\n- 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\n- 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\n- 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\n- Patients Entering with C5 polymorphism: Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant\n- 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\n- Patients Entering with C5 polymorphism: Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening\n- Patients Entering with C5 polymorphism: Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol\n- Patients Entering with C5 polymorphism: Known hereditary complement deficiency\n- Patients Entering with C5 polymorphism: Documented history of active, uncontrolled, ongoing systemic autoimmune diseases"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Incidence of treatment-emergent serious adverse events (SAEs)\n- Severity of treatment-emergent SAEs\n- Incidence of treatment emergent adverse events of special interest (AESIs)\n- Severity of treatment emergent AESIs\n- Incidence of adverse events (AEs) leading to permanent treatment discontinuation\n- Severity of adverse events (AEs) leading to permanent treatment discontinuation\n- Percent change from baseline in lactate dehydrogenase (LDH)","definition_or_measurement_approach":""}
Secondary endpoints
- {"endpoint_text":"- Adequate control of hemolysis (LDH ≤1.5 × ULN)\n- Transfusion avoidance\n- Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)\n- Hemoglobin stabilization\n- Percent change in LDH\n- Change in fatigue\n- Change in physical function (PF) scores on the EORTC QLQ-C30\n- Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30\n- Normalization of LDH\n- Rate of red blood cell (RBC) transfusion\n- Number of units of RBC transfusion\n- Percentage of days with LDH ≤1.5x upper limit of normal (ULN)\n- Change in hemoglobin levels\n- Change in total complement hemolytic activity assay (CH50)\n- Percent change in CH50\n- Concentrations of total pozelimab in serum\n- Concentrations of cemdisiran in plasma\n- Incidence of treatment-emergent anti-drug antibodies to pozelimab\n- Incidence of treatment-emergent anti-drug antibodies to cemdisiran\n- Concentration of total complement component 5 (C5) in plasma\n- Percent change of concentration of total C5 in plasma","definition_or_measurement_approach":"- Adequate control of hemolysis: LDH ≤1.5 × ULN\n- Breakthrough hemolysis: defined as LDH ≥2 × ULN (subsequent to initial achievement of LDH ≤1.5 × ULN) concomitant with signs or symptoms associated with hemolysis\n- Percentage/Percent change endpoints: measured using LDH laboratory values as specified in the endpoint text\n- PRO endpoints (fatigue, PF, GHS/QOL): measured using EORTC QLQ-C30 or specified PRO instruments\n- PK/PD and immunogenicity endpoints (pozelimab, cemdisiran, anti-drug antibodies, C5, CH50): measured by serum/plasma assays as described in the protocol"}
Recruitment
- Planned Sample Size
- 185
- Recruitment Window Months
- 71
- Consent Approach
- Informed consent is obtained from adult participants via subject information and informed consent forms (multiple country- and language-specific versions are provided). Materials include Main ICFs and variant ICF documents (e.g., FBR, PGX, PP) and recruitment/informed consent procedure documents (K1) for participating countries. Emergency/safety patient cards and translations (English plus local languages such as Italian, Hungarian, Polish, Romanian, Spanish, Greek) are provided. No pediatric assent process is indicated (trial population described as adults).
Methods
- Patients entering from the parent study R3918-PNH-2021 (NCT05133531) (explicitly stated as source of participants).
- Site-based recruitment per country-specific recruitment arrangements (recruitment arrangements documents (K1) and ICFs available for Italy, Hungary, Poland, Romania, Spain, Greece).
Geography
- Total Number Of Sites
- 15
- Total Number Of Participants
- 17
Italy
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 03-11-2025
- Processing Time Days
- 356
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Hematology
- Contact Person Name
- Simona Sica
- Contact Person Email
- simona.sica@unicatt.it
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- Hematology
- Contact Person Name
- Chiara Frairia
- Contact Person Email
- cfrairia@cittadellasalute.to.it
- Site Name
- Azienda Ospedaliero Universitaria Careggi
- Department Name
- Hematology
- Contact Person Name
- Barbara Scappini
- Contact Person Email
- scappinib@aou-careggi.toscana.it
Hungary
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 04-11-2025
- Processing Time Days
- 357
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Semmelweis University
- Department Name
- Hematology
- Contact Person Name
- Zsolt Nagy
- Contact Person Email
- nagy.zsolt@med.semmelweis-univ.hu
Poland
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 03-11-2025
- Processing Time Days
- 356
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Instytut Hematologii I Transfuzjologii
- Department Name
- Klinika Hematologii
- Contact Person Name
- Bozena Katarzyna Budziszewska
- Contact Person Email
- bbudziszewska@ihit.waw.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Hematologii i Transplantologii
- Contact Person Name
- Agnieszka Piekarska
- Contact Person Email
- agnieszka.piekarska@gumed.edu.pl
- Site Name
- In Vivo Sp. z o.o.
- Department Name
- In Vivo Sp. z o.o.
- Contact Person Name
- Jaroslaw Czyz
- Contact Person Email
- jczyz@onet.pl
Romania
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 04-11-2025
- Processing Time Days
- 357
- Number Of Sites
- 3
- Number Of Participants
- 2
Sites
- Site Name
- Spitalul Clinic Judetean De Urgenta Targu Mures
- Department Name
- Hematology
- Contact Person Name
- Ioan Macarie
- Contact Person Email
- ioan.macarie@umfst.ro
- Site Name
- Spitalul Clinic Municipal Filantropia Craiova
- Department Name
- Hematology
- Contact Person Name
- Luminita Ocroteala
- Contact Person Email
- diaconu_luminita@yahoo.com
- Site Name
- Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
- Department Name
- Hematology
- Contact Person Name
- IOANA- CODRUTA RUS
- Contact Person Email
- codruta_21@yahoo.com
Spain
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 04-11-2025
- Processing Time Days
- 357
- Number Of Sites
- 4
- Number Of Participants
- 4
Sites
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Hematology
- Contact Person Name
- Anna Gaya Valls
- Contact Person Email
- agayav@clinic.cat
- Site Name
- Hospital Universitario Basurto
- Department Name
- Hematology
- Contact Person Name
- Cristina Barrenetxea
- Contact Person Email
- cristina.barrene@gmail.com
- Site Name
- Hospital General Universitario Morales Meseguer
- Department Name
- Hematology Service
- Contact Person Name
- Maria Luisa Lozano Almela
- Contact Person Email
- mllozano@um.es
- Site Name
- Hospital Universitario De Salamanca
- Department Name
- Hematology Service
- Contact Person Name
- Maria Belén Vidriales Vicente
- Contact Person Email
- mbvidri@usal.es
Greece
- Earliest CTIS Part Ii Submission Date
- 12-11-2024
- Latest Decision Or Authorization Date
- 04-11-2025
- Processing Time Days
- 357
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Geniko Nosokomeio Thessalonikis George Papanikolaou
- Department Name
- Hematology
- Contact Person Name
- Chrysavgi Lalayanni
- Contact Person Email
- luizana6@gmail.com
Sponsor
Primary sponsor
- Full Name
- Regeneron Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Ppd Inc.
- Responsibilities
- CRO
- Name
- PPD Global Ltd.
- Responsibilities
- CRO
- Name
- Pharmaceutical Product Development LLC
- Name
- Parexel International (IRL) Limited
- Responsibilities
- Sites contract management
Third parties
- {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Iqvia Holdings Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Study logo creation, design, branding, site toolkit and 2D animation.","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Yourway Transport Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"Specialty Lab Services","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Specialty Lab Services","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Sites contract management","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
- {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Cemdisiran
- Active Substance
- CEMDISIRAN
- Modality
- Oligonucleotide
- Routes Of Administration
- SUBCUTANEOUS INJECTION
- Route
- SUBCUTANEOUS INJECTION
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Investigational Product Name
- Pozelimab
- Active Substance
- POZELIMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- SUBCUTANEOUS USE
- Route
- SUBCUTANEOUS USE
- Authorisation Status
- Authorised
- Combination Treatment
- Yes
Related trials
Other published trials that may interest you.
- POZELIMAB for Paroxysmal nocturnal hemoglobinuria
- pegcetacoplan for Paroxysmal nocturnal hemoglobinuria
- DANICOPAN for Paroxysmal nocturnal hemoglobinuria
- CROVALIMAB for Paroxysmal nocturnal hemoglobinuria
- (S)-4,5-DIHYDRO-2-[2-HYDROXY-4-(3,6-DIOXAHEPTYLOXY)PHENYL]-4-METHYL-4-THIAZOLECARBOXYLIC ACID for Transfusion-dependent alpha thalassemia | Transfusion-dependent beta thalassemia | Low-risk myelodysplastic syndromes