A Study to Investigate the Tolerability, Safety,Pharmacokinetics and efficacy of GR1603 in subjects with Systemic Lupus Erythematosus ； GR1603 injection is a monoclonal antibody targeting IFNAR1, which can block IFNAR binding to type I interferons such as IFNα and be used to treat systemic lupus erythematosus.
This is a Phase Ib/Ⅱ,double blind, multiple-dose study to evaluate the pharmacokinetics (PK), safety，tolerability and efficacy of intravenously administered GR1603 in participants with active SLE despite receiving standard of care . Phase Ib is a multi-dose escalation phase in which 16 subjects are scheduled to enroll. A total of 120 subjects were randomly assigned to GR1603 injection low dose group, high dose group or placebo group in phase Ⅱ.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
136
6 subjects in GR1603 low dose，2 subjects in placebo
6 subjects in GR1603 high dose，2 subjects in placebo
low dose GR1603 monthly
Peking union Medical Hosipital
Beijing, Beijing Municipality, China
Adverse events(phase Ib)
to characterise the safety and tolerability of GR1603,including abnormal vital signs,laboratory tests,electrocardiogram and physical examination
Time frame: up to week 16
Number of participants who achieved BICLA response (phase Ⅱ)
BICLA respnse:reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B
Time frame: week 24
Cmax(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
AUC0-t(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
AUC0-∞(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
AUCss(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
Tmax(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
t1/2z(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
Vz(phaseⅠb）
Pharmacokinetic indices
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high dose GR1603 monthly
Placebo
Time frame: up to week 16
CLz(phaseⅠb）
Pharmacokinetic indices
Time frame: up to week 16
Number of participants who achieved SRI (4)(phase Ⅱ)
An SRI (4) responder defined as a participant who had a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to 4 points;
Time frame: up to week 28
Number of participants who achieved BICLA response(phase Ⅱ)
BICLA respnse:reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B
Time frame: up to week 28
Number of participants with a ≥50% reduction in CLASI activity score (phase Ⅱ)
CLASI:Cutaneous Lupus Erythematosus Disease Area and Severity Index
Time frame: up to week 28
Flare rate(phase Ⅱ）
A flare was defined as either 1 or more new BILAG-2004 A or 2 or more new BILAG-2004 B items compared to the previous visit
Time frame: up to week 28