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

Sponsor

Genrix (Shanghai) Biopharmaceutical Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06015230

Collaborator

(none)

136

Enrollment

Location

Arms

78.9

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Systemic	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	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 8, 2022

Anticipated Primary Completion Date :

Jun 10, 2028

Anticipated Study Completion Date :

Oct 4, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Cmax(phaseⅠb） [up to week 16]
Pharmacokinetic indices
AUC0-t(phaseⅠb） [up to week 16]
Pharmacokinetic indices
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
CLz(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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking union Medical Hosipital	Beijing	Beijing	China	100730

Sponsors and Collaborators

Genrix (Shanghai) Biopharmaceutical Co., Ltd.

Investigators

Principal Investigator: xiaofeng zeng, PHD, Peking Union Medical College Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genrix (Shanghai) Biopharmaceutical Co., Ltd.

ClinicalTrials.gov Identifier:

NCT06015230

Other Study ID Numbers:

GR1603-002

First Posted:

Aug 29, 2023

Last Update Posted:

Aug 29, 2023

Last Verified:

Jun 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Genrix (Shanghai) Biopharmaceutical Co., Ltd.

IFNR

Autoimmune Diseases

SLE

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic

Study Results

No Results Posted as of Aug 29, 2023