A Study to Compare SB12 (Proposed Eculizumab Biosimilar) to Soliris in Subjects With Paroxysmal Nocturnal Haemoglobinuria

Study Overview
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Brief Summary
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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.

Detailed Description
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Subjects will be randomised in a 1:1 ratio to either treatment sequence. Subjects randomly assigned to treatment with SB12 or Soliris® will receive 600 mg of eculizumab IV every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks until Week 52. 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.

Official Title
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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

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: SB12 (proposed eculizumab biosimilar)
* Drug: Soliris (eculizumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 or older Eculizumab-naïve patients with PNH Presence of the PNH white blood cell (WBC) clone ≥ 10% Documented LDH level ≥ 1.5 x ULN at Screening History of transfusion for anaemia within 12 months prior to Screening or having PNH-related symptoms at Screening Subjects must be vaccinated against Neisseria meningitides Exclusion Criteria: Previous treatment with any complement pathway inhibitors ANC ≤ 500/mm3 or Platelet count < 70,000/mm3 History of meningococcal disease History of bone marrow transplantation Known or suspected active bacterial/viral/fungal infection within 30 days Stable use of erythropoietic, corticosteroids, heparin, warfarin before randomisation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence I<br>Subjects who are randomised to initially receive SB12 will be switched to receive Soliris® at Week 26 | Drug: SB12 (proposed eculizumab biosimilar)<br>* 600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter<br>Drug: Soliris (eculizumab)<br>* 600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter<br>|
| Experimental: Treatment Sequence II<br>Subjects who are randomised to initially receive Soliris® will be switched to receive SB12 at Week 26 | Drug: SB12 (proposed eculizumab biosimilar)<br>* 600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter<br>Drug: Soliris (eculizumab)<br>* 600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemolysis as measured by Lactate dehydrogenase (LDH) | Parallel comparison | Week 26 | 
| Hemolysis as measured by LDH | Crossover comparison | Week 52 |