A Phase Ib/II Study of Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection in Chinese Participants With Acute Gout

A Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection in Chinese Participants With Acute Gout

The purpose of this study is to determine the target dose of phase II and to evaluate the safety, tolerability, pharmacokinetics and efficacy of recombinant anti-IL-1β humanized monoclonal antibody injection at different doses in Chinese participants with acute gout.

Study Overview

• Status: Recruiting
• Conditions: Acute Gout
• Intervention / Treatment: Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 100 mg (phase Ib); Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 200 mg (phase Ib); Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 300 mg (phase Ib); Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 200 mg (phase II); Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection low dose 300 mg (phase II); Drug: Compound Betamethasone Injection (phase II); Other: Placebo (phase II)

Detailed Description

The phase Ib study is a multi-center, open label, dose escalation study examining the effect of recombinant anti-IL-1β humanized monoclonal antibody injection and to determine the target dose of phase II for the treatment of acute flare in Chinese gout patients in whom non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine are contraindicated, are not tolerated, or do not provide an adequate response. There are 3 dose groups (100 mg、200 mg and 300 mg) in phase Ib and 10 participants in each group.

The phase II study is a dose-ranging, multi-center, randomized, double-blind, double-dummy, active-controlled, parallel-group study examining the effect of 2 dose regimens (200 mg and 300 mg, based on the outcome of phase Ib) of recombinant anti-IL-1β humanized monoclonal antibody injection versus compound betamethasone injection for the treatment of acute flare in Chinese gout patients in whom NSAIDs and/or colchicine are contraindicated, are not tolerated, or do not provide an adequate response. The phase II recommended dose of SSGJ-613 in subjects with acute gouty was determined according to the phase Ib interim analysis results.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qinghong Zhou, MD; Phone Number: +86 18911301578; Email: zhouqinghong@3sbio.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Site 02
      • Contact: Lingli Dong, MD; Phone Number: +86 027-83665518; Email: tjhdongll@163.com
  • Shandong
    • Linyi, Shandong, China, 276100
      • Not yet recruiting
      • Site 03
      • Contact: Zhenchun Zhang, MD; Phone Number: +86 0539-8096886; Email: zzclyh@126.com
      • Principal Investigator: Zhenchun Zhang
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Site 01
      • Contact: Hejian Zou, MD; Phone Number: +86 13311881366; Email: hjzou@fudan.edu.cn
      • Principal Investigator: Hejian Zou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be 18 Years to 65 Years, both male and female
• Meeting the American College of Rheumatology (ACR) 2015 criteria for the classification of acute arthritis of primary gout.
• Presence of acute gout flare for no longer than 7 days
• Baseline pain intensity > or = to 50 mm on the 0-100 mm VAS
• Contraindicated for, intolerant or unresponsive to NSAIDs, colchicine or both

Exclusion Criteria:

• Secondary gout (such as gout caused by chemotherapy, transplant gout, etc.)
• Evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
• Presence of severe renal function impairment
• Intolerance of subcutaneous and intramuscular injection
• Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment
• History of malignant tumor within 5 years before screening
• Live vaccinations within 3 months prior to the start of the study
• Use of forbidden therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSGJ-613 100 mg (phase Ib); Dose Arm 1 (phase Ib): SSGJ-613 100 mg subcutaneous (s.c) once. The s.c. injection could be administered into the abdomen or thigh.	Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 100 mg (phase Ib); 100 mg subcutaneous (s.c) once; Other Names: SSGJ-613 100 mg (phase Ib)
Experimental: SSGJ-613 200 mg (phase Ib); Dose Arm 2 (phase Ib): SSGJ-613 200 mg subcutaneous (s.c) once. The s.c. injection could be administered into the abdomen or thigh.	Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 200 mg (phase Ib); 200 mg subcutaneous (s.c) once; Other Names: SSGJ-613 200 mg (phase Ib)
Experimental: SSGJ-613 300 mg (phase Ib); Dose Arm 3 (phase Ib): SSGJ-613 300 mg subcutaneous (s.c) once. The s.c. injection could be administered into the abdomen or thigh.	Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 300 mg (phase Ib); 300 mg subcutaneous (s.c) once; Other Names: SSGJ-613 300 mg (phase Ib)
Experimental: SSGJ-613 200 mg (phase II); Dose Arm 4 (phase II): SSGJ-613 200 mg subcutaneous (s.c) once. The s.c. injection could be administered into the abdomen or thigh. Randomized patients will receive one s.c. injection of SSGJ-613 and placebo matching compound betamethasone injection (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection is recommended to be administered deeply into the gluteal muscle.	Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection 200 mg (phase II); one s.c. injection of SSGJ-613 once, on Day 1.; Other Names: SSGJ-613 200 mg (phase II)
Experimental: SSGJ-613 300 mg (phase II); Dose Arm 5 (phase II): SSGJ-613 300 mg subcutaneous (s.c) once. The s.c. injection could be administered into the abdomen or thigh. Randomized patients will receive one s.c. injection of SSGJ-613 and placebo matching compound betamethasone injection (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection is recommended to be administered deeply into the gluteal muscle.	Drug: Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection low dose 300 mg (phase II); one s.c. injection of SSGJ-613 once, on Day 1.; Other Names: SSGJ-613 300 mg (phase II)
Active Comparator: Compound Betamethasone Injection 1 mL (phase II); Dose Arm 6 (phase II): Compound betamethasone injection 1 mL intramuscularly (i.m) once. The i.m. injection is recommended to be administered deeply into the gluteal muscle. Randomized patients will receive compound betamethasone injection 1 mL i.m. once and placebo matching SSGJ-613 s.c. once, on Day 1.	Drug: Compound Betamethasone Injection (phase II); 1 mL i.m. once on Day 1; Other: Placebo (phase II); Participants will receive Placebo matching SSGJ-613 to maintain the blinding of the Investigational Medicinal Products.; Other Names: PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	To investigate the safety characteristics.	From baseline through 24 weeks
Phase Ib: Incidence and Severity of Abnormalities in Vital Signs/Physical Examinations, Laboratory Examinations and Other Relevant Examinations	To investigate the safety characteristics.	From baseline through 24 weeks
Phase II: The Change in Pain Intensity in the Target Joint From Baseline to 72 Hours Post Dose as Measured on a 0-100 mm Visual Analog Scale (VAS)	The change in pain intensity from baseline to 72 hours post dose as measured on a 0-100 mm Visual Analog Scale (VAS): 0= no pain and 100= severe pain. Change from baseline = (post-baseline measurement - baseline).	Baseline, at 72 hrs post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Pharmacokinetic (PK) Cmax	PK parameters (Cmax) following single dose.	From baseline through 24 weeks
Phase Ib: Pharmacokinetic (PK) Tmax	PK parameters (Tmax) following single dose.	From baseline through 24 weeks
Phase Ib: Pharmacokinetic (PK) AUC 0-t	PK parameters (AUC 0-t) following single dose.	From baseline through 24 weeks
Phase Ib: Pharmacokinetic (PK) AUC 0-∞	PK parameters (AUC 0-∞) following single dose.	From baseline through 24 weeks
Phase Ib: Pharmacokinetic (PK) t1/2	PK parameters (t1/2) following single dose.	From baseline through 24 weeks
Phase Ib: The Pain Intensity in the Target Joint at 6, 12, 24, 48, 72 Hours, 4, 5, 6, 7 Days, and 4, 8, 12, 16, 20, 24 Weeks Post Dose as Measured on a 0-100 mm Visual Analog Scale (VAS)	The pain intensity post dose as measured on a 0-100 mm Visual Analog Scale (VAS): 0= no pain and 100= severe pain.	At 6, 12, 24, 48, 72 Hours, 4, 5, 6, 7 Days, and 4, 8, 12, 16, 20, 24 Weeks post-dose
Phase II: The Pain Intensity in the Target Joint at 6, 12, 24, 48, 72 Hours, 4, 5, 6, 7 Days, and 4, 8, 12 Weeks Post Dose as Measured on a 0-100 mm Visual Analog Scale (VAS)	The pain intensity post dose as measured on a 0-100 mm Visual Analog Scale (VAS): 0= no pain and 100= severe pain.	At 6, 12, 24, 48, 72 Hours, 4, 5, 6, 7 Days, and 4, 8, 12 Weeks post-dose
The Change in Pain Intensity in the Target Joint From Baseline to 6, 12, 24, 48 Hours Post Dose as Measured on a 0-100 mm Visual Analog Scale (VAS)	The change in pain intensity from baseline to 6, 12, 24, 48 hours post dose as measured on a 0-100 mm Visual Analog Scale (VAS): 0= no pain and 100= severe pain. Change from baseline = (post-baseline measurement - baseline).	Baseline, at 6, 12, 24, 48 hrs post-dose
The Time to At Least 50% Reduction of Baseline Pain Intensity in the Target Joint Within 7 Days after study drug administration	The time to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group, is estimated using the Kaplan Meier method. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100).	Baseline, within 7 days after study drug administration
The Time to Complete Pain Remission of Baseline Pain Intensity in the Target Joint Within 12 Weeks after study drug administration	The time to complete pain remission in Pain intensity from baseline as measured by a 5-point Likert scale for each treatment group, is estimated using the Kaplan Meier method. Participants scored their pain intensity in the target joint on a 5-point Likert scale: None, mild, moderate, severe, extremely severe.	Baseline, within 12 weeks after study drug administration
Percentage of Participants Taking Rescue Medication Within 7 Days After Study Drug Administration	Participants who had difficulty in tolerating their pain after the 12 and 72 hours post-dose pain assessments were allowed to take rescue medication.	7 days after study drug administration

Collaborators and Investigators

• Sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
• Investigators: Study Director: Qinghong Zhou, MD, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.; Principal Investigator: Hejian Zou, MD, Shanghai Huanshan Hospital Fudan University-Rheumatology

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Arthritis, Gouty; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Antibodies; Immunoglobulins; Betamethasone; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: SSGJ-613-AG-Ib/II-01

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