Health Condition 1: D595- Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
Conditions
Interventions
Intervention1: 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 (maint
Sponsors
Samsung Bioepis Co Ltd
PPD Pharmaceuticals India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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).Timepoint: 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
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of SB12 compared to Soliris® by -LDH profile over time -Number of units of packed red blood cells (pRBCs) transfused Timepoint: Efficacy endpoints •LDH profile over time •Number of units of pRBCs transfused throughout the study duration for each period ;To evaluate the immunogenicity of SB12 compared to Soliris®Timepoint: 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®Timepoint: PD endpoint •Terminal complement activity at Weeks 0 (Day 1),2,4,6,10,14,26,28,30,32,36,40,and 52 ;To evaluate the pharmacokinetic (PK) of SB12 compared to Soliris®Timepoint: 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 safety and tolerability of SB12 compared to Soliris®Timepoint: 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. | — |
Countries
China, India, Malaysia, Mexico, Republic of Korea, Romania, Taiwan, Thailand, Turkey, Ukraine
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed