Paroxysmal Nocturnal Hemoglobinuria
Conditions
Brief summary
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
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.
Interventions
DRUGSB12 (proposed eculizumab biosimilar)
600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter
DRUGSoliris (eculizumab)
600 mg IV every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter
Sponsors
Samsung Bioepis Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lactate Dehydrogenase (U/L) at Week 26 | Week 26 |
| Time-adjusted AUEC of LDH From Week 14 to Week 26 and From Week 40 to Week 52 | From Week 14 to Week 26 and from Week 40 to Week 52 |
Countries
India, Malaysia, Mexico, Romania, South Korea, Taiwan, Thailand, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Soliris to SB12 Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomized to initially receive Soliris were switched to receive SB12 at Week 26. | 25 |
| SB12 to Soliris Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomized to initially receive SB12 were switched to receive Soliris at Week 26. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 1 |
| Period 1 | Death | 1 | 0 |
| Period 1 | Pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | SB12 to Soliris | Total | Soliris to SB12 |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 13.44 | 38.1 years STANDARD_DEVIATION 13.55 | 36.3 years STANDARD_DEVIATION 13.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 27 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 18 Participants | 11 Participants |
| Sex: Female, Male Female | 8 Participants | 22 Participants | 14 Participants |
| Sex: Female, Male Male | 17 Participants | 28 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 1 / 47 |
| other Total, other adverse events | 18 / 47 | 11 / 47 |
| serious Total, serious adverse events | 3 / 47 | 2 / 47 |
Outcome results
Primary
Lactate Dehydrogenase (U/L) at Week 26
Time frame: Week 26
Population: Per-Protocol Set for LDH at a Single Time Point
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SB12 | Lactate Dehydrogenase (U/L) at Week 26 | 284.20 U/L | Standard Deviation 456.73 |
| Soliris | Lactate Dehydrogenase (U/L) at Week 26 | 249.72 U/L | Standard Deviation 103.67 |
95% CI: [-47.66, 116.62]
Primary
Time-adjusted AUEC of LDH From Week 14 to Week 26 and From Week 40 to Week 52
Time frame: From Week 14 to Week 26 and from Week 40 to Week 52
Population: Per-Protocol Set for AUEC of LDH
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SB12 | Time-adjusted AUEC of LDH From Week 14 to Week 26 and From Week 40 to Week 52 | 279.65 U/L | Standard Deviation 325.37 |
| Soliris | Time-adjusted AUEC of LDH From Week 14 to Week 26 and From Week 40 to Week 52 | 258.73 U/L | Standard Deviation 95.09 |
90% CI: [0.95, 1.23]