Lupus Erythematosus, Systemic
Conditions
Keywords
IFNR, Autoimmune Diseases, SLE
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALlow dose GR1603 in phase Ⅰb
6 subjects in GR1603 low dose，2 subjects in placebo
BIOLOGICALhigh dose GR1603 in phaseⅠb
6 subjects in GR1603 high dose，2 subjects in placebo
BIOLOGICALlow dose GR1603 in phase Ⅱ
low dose GR1603 monthly
BIOLOGICALhigh dose GR1603 in phase Ⅱ
high dose GR1603 monthly
BIOLOGICALPlacebo in phase Ⅱ
Placebo
Sponsors
Genrix (Shanghai) Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SLE according to the ACR 1997 ≥24 weeks * Active moderate to severe SLE * At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
Exclusion criteria
* Active severe or unstable neuropsychiatric SLE * Clinically significant laboratory test * Clinically significant active infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events(phase Ib) | up to week 16 | to characterise the safety and tolerability of GR1603,including abnormal vital signs,laboratory tests,electrocardiogram and physical examination |
| Number of participants who achieved BICLA response (phase Ⅱ) | week 24 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| AUCss(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| Tmax(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| t1/2z(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| Vz(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| Cmax(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| Number of participants who achieved SRI (4)(phase Ⅱ) | up to week 28 | 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; |
| Number of participants who achieved BICLA response(phase Ⅱ) | up to week 28 | 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 |
| Number of participants with a ≥50% reduction in CLASI activity score (phase Ⅱ) | up to week 28 | CLASI:Cutaneous Lupus Erythematosus Disease Area and Severity Index |
| Flare rate(phase Ⅱ） | up to week 28 | 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 |
| CLz(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
| AUC0-t(phaseⅠb） | up to week 16 | Pharmacokinetic indices |
Countries
China
Outcome results
None listed