Clinical Study of Genakumab for Injection in Patients With Acute Gout

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of single subcutaneous injection of Genakumab for Injection in patients with acute gout

Detailed Description
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Phase Ib: single arm, open lable, single dose, dose escalation,design. There are 3 dose groups with 10 participant s in each group. Phase II: randomized, double-blind, active control design.There are 2 dose groups of Genakumab for Injection with 30 participant s in each group and 1 group of Compound Betamethasone Injection with 30 praticipants.

Official Title
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The Phase Ib/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Genakumab for Injection in Patients With Acute Gout

Conditions
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Acute Gout

Intervention / Treatment
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* Drug: Genakumab for Injection
* Drug: Placebo for Genakumab for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years ≤ age ≤65 years Meeting the American College of Rheumatology (ACR) 2015 preliminary criteria for the classification of acute arthritis of primary gout Contraindication, intolerance or lack of efficacy for NSAIDs and/or colchicine Body mass index of less than or equal to 45 kg/m2 Onset of current acute gout flare within 5 days prior to study entry Baseline pain intensity ≥ 50 mm on the 0-100 mm visual analog scale (VAS) History of gout flare prior to study entry Exclusion criteria: evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis Presence of severe renal function impairment Use of specified pain relief medications or biologics ( corticosteroids, narcotics, paracetamol/acetominophen, ibuprofen, colchicine, IL-blocker, and tumor necrosis factor inhibitor) within specified periods prior to study entry Live vaccinations within 3 months prior to randomization Requirement for administration of antibiotics against latent tuberculosis (TB) Any active or recurrent bacterial, fungal, or viral infection QTc>450ms for male, QTc>470ms for female

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Group A : 50mg by single subcutaneous injection; Group B : 100mg by single subcutaneous injection Group C : 195mg by single subcutaneous injection;Group D : 100mg by single subcutaneous injection Group E : 195mg by single subcutaneous injection; Group F: 1ML Compound Betamethasone Injection by single intramuscular injection
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genakumab for injection 50mg (Ib)<br>subcutaneous injection, single dose | Drug: Genakumab for Injection<br>* 150 mg/1ml/bottle<br>|
| Experimental: Genakumab for injection 100mg (Ib)<br>subcutaneous injection, single dose | Drug: Genakumab for Injection<br>* 150 mg/1ml/bottle<br>|
| Experimental: Genakumab for injection 195mg (Ib)<br>subcutaneous injection, single dose | Drug: Genakumab for Injection<br>* 150 mg/1ml/bottle<br>|
| Experimental: Genakumab for injection 100mg (II)<br>Genakumab for injection, subcutaneous injection, single dose Placebo for Compound Betamethasone Injection, intramuscular injection, single dose | Drug: Genakumab for Injection<br>* 150 mg/1ml/bottle<br>|
| Experimental: Genakumab for injection 195mg (II)<br>Genakumab for injection, subcutaneous injection, single dose Placebo for Compound Betamethasone Injection, intramuscular injection, single dose | Drug: Genakumab for Injection<br>* 150 mg/1ml/bottle<br>|
| Active Comparator: Compound Betamethasone Injection 1ml (II)<br>Compound Betamethasone Injection, 1 ml, intramuscular injection, single dose Placebo for Genakumab for injection, 100mg, subcutaneous injection, single dose | Drug: Placebo for Genakumab for Injection<br>* The placebo contains other excipients except Genakumab, and its appearance is consistent with that of Genakumab for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Blood samples will be collected at indicated time points for pharmacokinetic analysis. | baseline, 24hours, 48hours, 120hours, Day 7, Day 14, Day 21, Day 28, Day 56, Day 84, Day 112 | 
| pain intensity change from baseline to 72 hours post dose as measured on a 0-100 mm Visual Analog Scale (VAS) | 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain | 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Adverse events (AEs) were defined as any unfavourable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards | up to 16 weeks | 
| High Sensitivity C-reactive Protein (hsCRP) | High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (except Visit 2 and Visit 4 ) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. | at 72 hours and 7 days, 4, 8 and 12 weeks post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute gout