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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking union Medical Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genrix (Shanghai) Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: xiaofeng zeng, PHD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2022
• Primary Completion (Estimated): June 10, 2028
• Study Completion (Estimated): October 4, 2028

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: SLE; Autoimmune Diseases; IFNR
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: GR1603-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No