A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY, OF SA237 AS MONOTHERAPY IN PATIENTS WITH NEUROMYELITIS OPTICA (NMO) AND NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD),
- Clements University Hospital
- Parkland Health & Hospital System
- UT Southwestern Ambulatory Services
Benjamin Greenberg, M.D.
This Phase 3 pivotal study is a multicenter randomized, double-blind, placebo-controlled parallel assignment study followed by an open-label extension period. Patients will be randomized to two groups (2:1, Group a or B) and will receive subcutaneous Sa237 (Group a) or placebo (Group B) at Weeks 0, 2 and 4, and Q4W thereafter. The number of patients who are negative for anti-aQP4 antibody at screening will be limited to 30% of total study population. The randomization will be stratified by prior therapy for prevention of nMo/nMoSD attack (B-cell depleting therapy or immunosuppressants/others) and the most recent attack in the last one year prior to screening (first attack or relapse).
Patients who experience a relapse in the double-blind period or complete the double-blind period without any relapse can enter the open-label extension period. in the extension period, patients will receive open-label treatment with 120 mg Sa237 SC at Wks 0, 2 and 4 and every 4 weeks (Q4W) thereafter, for approximately 1 year (last administration is Wk 48). For patients who experience a relapse in the double-blind period, appropriate rescue therapy for relapse will be conducted and Sa237 should start in the stable disease condition (Day 31 or later but not more than 60 days, where Day 1 is defined as the day of onset of relapse in the double-blind period).
Those patients who complete the double-blind period (up to 48 weeks) without experiencing relapse will be instructed to return to the study site 4 weeks ((+-)7 days) after the last dosing in order to undergo the Day 1 assessments for the extension period. For those patients who enter the extension period after a relapse, the Day 1 assessments of the extension phase will occur 31-60 days after the onset of relapse. The extension period is expected to last approximately 1 year (last administration is Wk 48).
Those patients who experience 2 relapses in the extension period, both with a more severe intensity than the last relapse prior to baseline must be discontinued from treatment . it is the investigator's decision whether the patient can continue in the extension period. if the relapses aren't as severe as the relapse prior to baseline they can remain in the extension period without being limited to the total number of relapses.
efficacy outcome Variables
1. Primary endpoint
a. Time to First Relapse (TFR) in the double-blind period.
2. Secondary endpoints
a. Change in Visual analogue Scale for Pain (VaS) score for pain
b. Change in Functional assessment of Chronic illness Therapy (FaCiT) fatigue score
c. Change Health Status Measurements using Short Form-36 (SF-36) score
d. Change in eQ-5D score (The eQ-5D scale is a generic measure of health related quality of life that rates subject health state)
e. Change in Timed 25-Foot Walk (T25W) score
f. The proportion of relapse-free patients
g. annualized Relapse Rate (aRR)
h. Change in Modified Rankin Scale (mRS) score
i. Change in Zarit Burden interview (ZBi) score
j. Change in expanded Disability Status Scale (eDSS) score
k. Change in visual acuity (Snellen chart)
l. Change in low-contrast visual acuity (byLow-contrast Sloan Letter Chart - LCSLC)
Safety outcome Variables
a. incidence and severity of aes, Saes and aeSis.
b. Vital signs, physical exam, clinical laboratory tests, eCG, suicidality (Columbia-Suicide Severity Rating Scale - C-SSRS).
a. MRi scans of the brain, optic nerve and spinal cord
MRi for exploratory evaluation is optional and will be conducted at selected sites.
Pharmacodynamic (PD)outcome Variables
d. anti-aQP4 antibodies
Pharmacokinetic (PK) outcome Variables
a. Serum Sa237 concentration
2. immunogenicity outcome Variables
a. incidence of anti-Sa237 antibodies
b. ( PD) ,(PK), clinical response, and safety during the study by anti-Sa237 antibody status
1. Patients must be diagnosed as either:
a. NMO as defined all of the following criteria:
I. Optic neuritis
II. Acute myelitis
III. At least two of three supportive criteria:
*Contiguous spinal cord lesion identified on an MRI scan extending over 3 vertebral segments
*Brain MRI not meeting diagnostic criteria for multiple sclerosis
b. NMOSD as defined by either of following criteria with anti-AQP4 antibody seropositive status at screening.
*Idiopathic single or recurrent events of longitudinally extensive myelitis (>=3 vertebral segment spinal cord MRI lesion)
*Optic neuritis, single, recurrent or simultaneous bilateral
2. Clinical evidence of at least 1 documented relapse (including first attack) in the last 12 months prior to screening.
3. EDSS score from 0 to 6.5 inclusive at screening.
4. Age 18 to 74 years, inclusive at the time of informed consent.
5. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol.