Clinical Study to Investigate the Safety, Tolerability, and Pharmacokinetics of GR1603 in SLE

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase Ⅰb/Ⅱ, Randomized, Double-blind, Placebo-controlled Study to Investigate the Tolerability, Safety,Pharmacokinetics and Efficacy of an Intravenous Treatment Regimen of GR1603 in Subjects With Systemic Lupus Erythematosus

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Biological: low dose GR1603 in phase Ⅰb
* Biological: high dose GR1603 in phaseⅠb
* Biological: low dose GR1603 in phase Ⅱ
* Biological: high dose GR1603 in phase Ⅱ
* Biological: Placebo in phase Ⅱ


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group 1-Ⅰb<br>6 subjects in GR1603 low dose，2 subjects in placebo | Biological: low dose GR1603 in phase Ⅰb<br>* 6 subjects in GR1603 low dose，2 subjects in placebo<br>|
| Experimental: Treatment group 2-Ⅰb<br>6 subjects in GR1603 high dose，2 subjects in placebo | Biological: high dose GR1603 in phaseⅠb<br>* 6 subjects in GR1603 high dose，2 subjects in placebo<br>|
| Experimental: treatment group 3-Ⅱ<br>low dose GR1603 monthly | Biological: low dose GR1603 in phase Ⅱ<br>* low dose GR1603 monthly<br>|
| Experimental: treatment group 4-Ⅱ<br>high dose GR1603 monthly | Biological: high dose GR1603 in phase Ⅱ<br>* high dose GR1603 monthly<br>|
| Placebo Comparator: treatment group 5-Ⅱ<br>placebo | Biological: Placebo in phase Ⅱ<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events(phase Ib) | to characterise the safety and tolerability of GR1603,including abnormal vital signs,laboratory tests,electrocardiogram and physical examination | 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 | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| AUC0-t(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| AUC0-∞(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| AUCss(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| Tmax(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| t1/2z(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| Vz(phaseⅠb） | Pharmacokinetic indices | up to week 16 | 
| CLz(phaseⅠb） | Pharmacokinetic indices | 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; | 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 | 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 | 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 | up to week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, IFNR, Autoimmune Diseases