| CTRI Number |
CTRI/2024/04/065519 [Registered on: 10/04/2024] Trial Registered Prospectively |
| Last Modified On: |
13/11/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Drug
Biological |
| Study Design |
Non-randomized, Multiple Arm Trial |
Public Title of Study
Modification(s)
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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) |
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Scientific Title of Study
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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 |
| Trial Acronym |
NIL |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2021-004931-10 |
EudraCT |
| 2023-510336-36-00 |
Other |
| NCT05744921 |
ClinicalTrials.gov |
| R3918-PNH-2050 Protocol Amendment 5 Dated 13 May 2025 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership- BIOTECH CLIENT DELIVERY MANAGEMENT |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
Bangalore
KARNATAKA
560103
India |
| Phone |
918067723000 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@parexel.com |
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Details of Contact Person
Public Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership- BIOTECH CLIENT DELIVERY MANAGEMENT |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
KARNATAKA
560103
India |
| Phone |
918067723000 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@parexel.com |
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Source of Monetary or Material Support
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| Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road
Tarrytown, NY 10591
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Primary Sponsor
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| Name |
Regeneron Pharmaceuticals, Inc. |
| Address |
777 Old Saw Mill River Road, Tarrytown, NY 10591 |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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| Name |
Address |
| PAREXEL International Clinical Research Private Limited |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU – 560103, Karnataka, INDIA |
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Countries of Recruitment
Modification(s)
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Canada
Colombia
Hungary
India
Italy
Japan
Jordan
Malaysia
Mexico
Peru
Philippines
Poland
Republic of Korea
Romania
Singapore
Spain
Taiwan
Thailand
Turkey
United Kingdom |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Neeraj Sidharthan |
Amrita Institute of Medical Sciences and Research Centre |
Room No.-NAP, Division- NAP, Department of Clinical Hematology and Stem Cell Transplant Unit, AIMS Ponekkara, P O, Kochi - 682041
Ernakulam
KERALA |
9946047464
neerajsidh@gmail.com |
| Dr Upendra Sharma |
Bhagwan Mahaveer Cancer Hospital and Research Center |
Room No-NAP, Division -NAP, Department of Hemato-Oncology
Jawaharlal Nehru Marg-302017
Jaipur
RAJASTHAN |
1412700107
drupendra.sharma@yahoo.co.in |
| Dr Shrinath Kshirsagar |
K. J. Somaiya Hospital and Research Centre |
3rd Floor, CTRU,
SS building, Somaiya Ayurvihar Complex, Eastern Express Highway, Sion (East)- 400022, India.
Mumbai
MAHARASHTRA |
2235306587
shrinath@somaiya.edu |
| Dr Shailendra Prasad Verma |
King Georges Medical University |
Room No-NAP, Department of clinical Hematology,
Shatabdi phase 2,
6th floor,KGMU,
Chowk-226003
Lucknow
UTTAR PRADESH |
05222258880
drspkgmu@rediffmail.com |
| Dr Chandran Kuruvattu |
Malabar Cancer Centre |
Room No-NAP, Division -NAP, Department of Clinical Hematology and Medical Oncology, P.O. Moozhikkara, Thalassery-670103
Kannur
KERALA |
04902355881
drchandrannair1989@gmail.com |
| Dr Gaurav Prakash |
Post Graduate Institute of Medical Education and Research |
Room no- 17-D, 4th Floor Division- F Block, Department of Clinical Hematology and Medical Oncology, Nehru Hospital, PGIMER, Sector-12-160012
Chandigarh
CHANDIGARH |
9914209678
drgp04@gmail.com |
| Dr Narendra Agrawal |
Rajiv Gandhi Cancer Institute and Research Centre |
Room No-NAP, Division -NAP, Department of Hemato-Oncology & BMT, Sector - 5, Rohini-110085.
New Delhi
DELHI |
01147022437
narendra_ag1@rediffmail.com |
| Dr Sanjeev |
Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) |
Room No.-NAP, Division- I Block, Department of Hematology, SGPSIMS, Raebareli Road-226014
Lucknow
UTTAR PRADESH |
91-9670187769
dr.sanjeev.ranchi@gmail.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences, Dr. Neeraj Sidharthan |
Submittted/Under Review |
| Institutional Ethics Committee, Bhagwan Mahaveer Cancer Hospital and Research Centre, Dr. Upendra Sharma |
Approved |
| Institutional Ethics Committee, K. J. Somaiya Medical College, Hospital, Dr Shrinath Kshirsagar |
Approved |
| Institutional Ethics Committee, King Georges Medical University, Dr S P Verma |
Approved |
| Institutional Ethics committee, Malabar Cancer Centre, Dr. Chandran Kuruvattu |
Submittted/Under Review |
| Institutional Ethics Committee, Post Graduate Institute of Medical Education and Research, Dr. Gaurav Prakash |
Submittted/Under Review |
| Institutional Ethics Committee, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Dr. Sanjeev |
Submittted/Under Review |
| Institutional Review Board, Rajiv Gandhi Cancer Institute and Research centre, Dr. Narendra Agrawal |
Submittted/Under Review |
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Regulatory Clearance Status from DCGI
Modification(s)
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D595||Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli], |
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Intervention / Comparator Agent
Modification(s)
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| Type |
Name |
Details |
| Intervention |
C5 Polymorphism Patients |
Pozelimab + Cemdisiran administered per the protocol.
Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ ravulizimab. Note: Loading dose of pozelimab administered IV on Day 1. |
| Intervention |
PNH Transition Patients |
Pozelimab + Cemdisiran administered per the protocol.
Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531]) |
| Comparator Agent |
There is no comparator for this study. |
There is no comparator for this study. |
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Inclusion Criteria
Modification(s)
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
(A) 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.
(B) 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 more than equals to 2 IN TO 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 |
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| ExclusionCriteria |
| Details |
(A) Patients Entering from the Parent Study -
1. 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 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
(B) 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 Inclusion OR Exclusion Criteria apply
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Method of Generating Random Sequence
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Other |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
(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) |
(1) Up to week 108
(2) Up to week 108
(3) Up to week 108
(4) Up to week 108
(5) Up to week 108
(6) Up to week 108
(7) Baseline to week 36
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Secondary Outcome
Modification(s)
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| Outcome |
TimePoints |
| Adequate control of hemolysis (LDH less than or equal to 1.5 IN TO ULN) |
Post-baseline through week 108 |
| Transfusion avoidance, defined as not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values |
Post-baseline through week 36,
48, 76 and 108
|
| Breakthrough hemolysis (defined as LDH greater than or equal to 2 IN TO ULN [subsequent to initial achievement of LDH less than or equal to 1.5 IN TO ULN] concomitant with signs or symptoms associated with hemolysis) |
Post-baseline through week 36, 48, 76 and 108 |
| Hemoglobin stabilization- Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per of greater than or equal to 2 g per dL |
Post-baseline through week 36, 48, 76 and 108 |
| Percent change in LDH |
From baseline to weeks 48, 76, and 108 |
| Change in fatigue as measured by the FACIT-Fatigue scale |
From baseline to weeks
36, 48, 76, and 108
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| Change in physical function (PF) scores on the EORTC QLQ-C30 |
From baseline to weeks 36, 48, 76 and 108 |
| Change in GHS OR quality of life scale on the EORTC QLQ C30 |
From baseline to weeks 36, 48, 76, and 108 |
| Normalization of LDH |
From post-baseline through week 108 |
Rate of red blood cell (RBC) transfusion
|
Postbaseline
through weeks 36, 48, 76, and 108
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| Number of units of RBC transfusion |
Postbaseline
through weeks 36, 48, 76, and 108
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| Percentage of days with LDH less than or equal to 1.5 IN TO upper limit of normal |
Post-baseline through Weeks 36, 48, 76, and 108 |
| Change in hemoglobin levels |
From baseline to weeks 36, 48, 76, and 108 |
| Change in total complement hemolytic activity assay |
Through week 108 |
| Percent change in CH50 |
Through week 108 |
| Concentrations of total pozelimab in serum |
Through week 108 |
| Concentrations of cemdisiran in plasma |
Through week 24 |
| Incidence of treatment-emergent anti-drug antibodies to pozelimab |
Through week 108 |
| Incidence of treatment-emergent anti-drug antibodies to cemdisiran |
Through week 108 |
| Concentration of total complement component 5 (C5) in plasma |
Through week 108 |
| Percent change of concentration of total C5 in plasma |
Through week 108 |
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Target Sample Size
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Total Sample Size="202"
Sample Size from India="25"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
|
01/05/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
07/03/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="6"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
Modification(s)
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This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as study drugs in this section. This study is looking at several other research questions, including: - How effective is the pozelimab + cemdisiran combination? - What side effects may happen from taking the study drugs? - How much of each study drug is in your blood at different times? - Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects). |