CTRI/2019/05/019148 [Registered on: 15/05/2019] Trial Registered Prospectively
Last Modified On:
13/02/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A study to compare SB12 (proposed eculizumab biosimilar) with Soliris® in patients with the disease Paroxysmal Nocturnal Haemoglobinuria
Scientific Title of Study
A Phase III Randomised, Double-blind, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity between SB12 (proposed eculizumab biosimilar) and Soliris® in Subjects with Paroxysmal Nocturnal Haemoglobinuria
Trial Acronym
SB12-3003
Secondary IDs if Any
Secondary ID
Identifier
SB12 3003, Protocol Version 3 dated 12 Dec 2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Amrita Institute of Medical Sciences and Research Centre (AIMS)
Department of Medical Oncology and Hematology
Peeliyadu Road, Ponekkara, Edappally
Kochi, Kerala – 682 041
Ernakulam KERALA
9946047464
neerajsidharthan@aims.amrita.edu
Dr Prabu Pandurangan
Apollo Speciality Hospital
Apollo Hospitals,
Apollo Hospitals Enterprise Limited,
21, Greams Lane, Off, Greams Road, Chennai - 600 006
Chennai TAMIL NADU
9003224487
drprabhu_p@apollohospitals.com
Dr Rahul Bhargava
Fortis Memorial Research Institute
Fortis Memorial Research Institute,
Sector 44, Gurgaon – 122002
Gurgaon HARYANA
9958174994
bhargava777@gmail.com
Dr Prakas Mandal
Nil Ratan Sircar Medical College and Hospital
Hematology Department, 138-A.J.C Bose Road, Kolkata - 700014, West Bengal. India. Kolkata WEST BENGAL
9433345001 03322123785 prakas70@gmail.com
Dr Gaurav Prakash
Postgraduate Institute of Medical Education and Research
Postgraduate Institute of Medical Education and
Research,
Sector-12, Chandigarh – 160 012
Chandigarh CHANDIGARH
600 mg every 7 days for the first 4 weeks (initial phase) and 900 mg for the fifth
week, followed by 900 mg every 14 ± 2 days until Week 52 (maintenance phase).
Intervention
SB12
(proposed eculizumab biosimilar)
600 mg every 7 days for the first 4 weeks (initial phase) and 900 mg for the fifth
week, followed by 900 mg every 14 ± 2 days until Week 52 (maintenance phase)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Male or female aged 18 or older at the time of signing the informed consent form (ICF), if local regulations are different in this regard, follow the local regulations.
2. Documented diagnosis of PNH.
3. Presence of the PNH white blood cell (WBC) clone more than or equal to 10% by high-sensitivity flow cytometry at Screening.
4. Documented LDH level more than or equal to 1.5 × upper limit of normal (ULN) at Screening.
5. History of transfusion for anaemia within 12 months prior to Screening or having PNH-related symptoms (e.g., fatigue, haemoglobinuria, abdominal pain, chest pain, shortness of breath [dyspnoea], dysphagia, erectile dysfunction) at Screening.
6. All subjects must be vaccinated against Neisseria meningitidis within 3 years prior to or on Day 1 in accordance with current local guidelines or Soliris ® Summary of Product Characteristics (SmPC) to reduce the risk of meningococcal infection.
7. Female subjects who are not pregnant or nursing at Screening and on initiation of study drug (Day 1) and who are not planning to become pregnant from Screening until 5 months after the last dose of study drug.
8. Subjects and their partners of childbearing potential (female or male) who agree to use of a highly effective contraceptive method (e.g., established use of oral, injected or implanted hormonal contraceptive, placement of an intrauterine device or intrauterine system, male sterilisation, or true abstinence [see Section 8.4.1]) from Screening until 5 months after the last dose of study drug.
9. Subjects must be able to understand the implications of taking part in the study and be willing to follow the study instructions and requirements fully.
10. Subjects must be able to provide informed consent, which must be obtained prior to any study related procedures.
ExclusionCriteria
Details
1. Previous treatment with a complement pathway inhibitor (including eculizumab).
2. Known hypersensitivity to the investigational product (IP) or any of the ingredients or excipients of the IP.
3. Known contraindication/hypersensitivity for meningococcal vaccine or the antibiotic to be used in the study.
4. Abnormal haematological parameters at Screening defined as the following:
a. Absolute neutrophil count (ANC) less than
or equal to 500/mm3
b. Platelet count less than 70,000/mm3
5. History of meningococcal disease.
6. History of bone marrow transplantation.
7. History of serious thrombotic event (e.g., stroke, myocardial infarction, pulmonary embolism, etc.).
8. Known or suspected active bacterial, virus, fungal infection within 30 days prior to initiation of study drug (Day 1).
9. Known history of human immunodeficiency virus (HIV) infection or have positive results at Screening.
10. Concomitant use of any of the following medications is prohibited if the following conditions apply.
a. Erythropoietin, systemic corticosteroids, low-molecular-weight heparins, iron supplements,and androgen therapy that has not been
on a stable dose for at least 4 weeks prior to initiation of study drug (Day 1).
b. Warfarin with an unstable international normalized ratio (INR) for at least 4 weeks prior to initiation of study drug (Day 1).
c. Cyclosporine that has not been on a stable dose for at least 8 weeks prior to initiation of study drug (Day 1).
11. Subjects who have received or participated in another investigational drug, device, or procedures within 30 days or within 5 half-lives of that IP prior to Screening, whichever is greater.
12. History of malignancy within 5 years prior to Screening, except for curatively treated carcinoma in situ of uterine cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
13. Any other cardiac, hepatic, immunologic, pulmonary, rheumatoid disease, other conditions causing rise in LDH (e.g., tumours, muscular dystrophies, liver and bile disease, etc.), or the disorder which, at the discretion of the Investigator, will put the subjects at risk if they are enrolled.
14. Other unspecified reasons that, at the discretion of the Investigator or Sponsor, make the subjects unsuitable for enrollment.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
The primary objective of this study is to demonstrate comparable clinical efficacy of SB12 and Soliris®, by evaluating the lactate dehydrogenase (LDH) in subjects with paroxysmal nocturnal haemoglobinuria (PNH).
1. LDH level (U/L) at Week 26
2. Area under the effect curve (AUEC) of LDH from Week 14 to Week 26 and from Week 40 to Week 52
Secondary Outcome
Outcome
TimePoints
To evaluate the efficacy of SB12 compared to Soliris® by
-LDH profile over time
-Number of units of packed red blood cells (pRBCs) transfused
Efficacy endpoints
•LDH profile over time
•Number of units of pRBCs transfused throughout the study duration for each period
To evaluate the safety and tolerability of SB12 compared to Soliris®
Safety endpoints
•Incidence of adverse events (AEs) and serious AEs (SAEs)
•Incidence of infection-related AEs
-Meningococcal infection
-Other systemic infections
•Incidence of infusion-related reactions (IRRs)
•Safety of subjects will be monitored by 12-lead electrocardiogram (ECG), vital sign assessment, and physical examination. Haematological, biochemical, and urinalysis laboratory parameters will be also measured.
To evaluate the pharmacokinetic (PK) of SB12 compared to Soliris®
PK endpoint
•Concentration prior to infusion (trough serum concentration [Ctrough]) at Weeks 0 (Day 1),2,4,6,10,14, 18,22,26,28,30,32,36,40,44, 48,and 52
To evaluate the immunogenicity of SB12 compared to Soliris®
Immunogenicity endpoints
•Incidence of anti-drug antibodies (ADAs) at Weeks 0 (Day 1),2,4,6,10,14,18,22,26,28, 30,32,36,40,44,48,52, and EOS/ET
•Incidence of neutralising antibodies (NAbs) at Weeks 0 (Day 1),2,4,6,10,14,18,22,26,28,30,32,36,40,44,48,52, and EOS/ET
To evaluate the pharmacodynamic (PD) of SB12 compared to Soliris®
Total Sample Size="50" Sample Size from India="15" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The primary objective of this study is to demonstrate comparable clinical efficacy of SB12 and Soliris®, by evaluating the lactate dehydrogenase (LDH) in subjects with paroxysmal nocturnal haemoglobinuria (PNH). This is a randomised Phase III, double-blind, multicentre, cross-over study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB12 and Soliris® in subjects with PNH. Subjects will be randomised in a 1:1 ratio to treatment sequence I (SB12 to Soliris®) or treatment sequence II (Soliris® to SB12). Subjects who are randomised to initially receive SB12 will be switched to receive Soliris® and subjects who are randomised to initially receive Soliris® will be switched to receive SB12 at Week 26.