Proof-of-concept Study to Assess the Efficacy, Tolerability and Safety of a Single Intraarticular Dose of GZ389988 Versus Placebo in Patients With Painful Osteoarthritis of the Knee

Phase 2

Completed

• Conditions: Osteoarthritis
• Interventions: Drug: placebo; Drug: GZ389988; Drug: acetaminophen or paracetamol; Drug: fixed combination of paracetamol + codeine; Drug: fixed combination of paracetamol + tramadol hydrochloride

• Registration Number: NCT02845271
• Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary

Primary Objective:

To assess the efficacy of a single intraarticular dose of GZ389988 compared to placebo for relief of knee pain in patients with osteoarthritis (OA) of the knee.

Secondary Objectives:

To assess the safety and tolerability of a single intraarticular dose of GZ389988 in patients with painful OA of the knee.

To assess the pharmacokinetic parameters of a single intraarticular dose of GZ389988 in patients with painful OA of the knee.

Detailed Description

Screening will be performed within 21 days of dosing. Following the single dose of study medication, the study period for each patient will be 84 ± 7 days up to the end-of-study visit.

Total duration for one patient will be up to 16 weeks (up to the end-of-study visit), not including the long-term observational safety follow-up phone call for 12 additional weeks.

The collection of primary endpoint data up to Week 4 for futility analysis is optional. Assuming a possible step-down in dose due to safety/tolerability reasons, the total expected maximum number of included patients could be increased up to a maximum of 182 patients.

Study Timeline

• Study First Submitted: 2016-07-19
• Study Start: 2016-07-21
• Study First Submitted QC: 2016-07-22
• Study First Posted: 2016-07-27
• Primary Completion: 2017-06-28
• Study Completion: 2017-09-13
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GZ389988	fixed combination of paracetamol + tramadol hydrochloride	Single intraarticular injection of GZ389988 in the knee joint
Placebo	placebo	Single intraarticular injection of placebo for GZ389988 in the knee joint
Placebo	acetaminophen or paracetamol	Single intraarticular injection of placebo for GZ389988 in the knee joint
Placebo	fixed combination of paracetamol + codeine	Single intraarticular injection of placebo for GZ389988 in the knee joint
GZ389988	GZ389988	Single intraarticular injection of GZ389988 in the knee joint
GZ389988	acetaminophen or paracetamol	Single intraarticular injection of GZ389988 in the knee joint
GZ389988	fixed combination of paracetamol + codeine	Single intraarticular injection of GZ389988 in the knee joint
Placebo	fixed combination of paracetamol + tramadol hydrochloride	Single intraarticular injection of placebo for GZ389988 in the knee joint

Primary Outcome Measures

Name	Time	Method
Change from baseline in weekly mean score of Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 pain subscore (walking pain) collected daily in the target knee, as measured by the Visual Analogue Scale (VAS) 0-100	Averaged over 4 weeks (up to Day 28)

Secondary Outcome Measures

Name	Time	Method
Change from baseline in weekly mean score of WOMAC A1 pain sub-score (walking pain) collected daily in the target knee, as measured by the VAS 0-100	Averaged over 12 weeks (up to Day 84)
Change from baseline in weekly mean score of WOMAC A1 pain sub-score collected daily in the target knee	At 1, 2, 3, 4, 6, 8, 10, and 12 weeks
Change from baseline in weekly mean score of overall knee pain collected daily in the target knee	At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks
Change from baseline in Patient Global Assessment (PGA) of disease status	At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks
Change from baseline in WOMAC index (total score for pain, stiffness, and physical function subscales), pain, stiffness and physical function sub-scores	Averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks
Patient Global Impression of Change (PGIC)	Over the last 4 weeks at Day 28 (1 to 4 weeks), Day 56 (5 to 8 weeks), and Day 84 (9 to 12 weeks)
Patient Global Assessment of Response to Therapy (PGART)	Over the last 4 weeks at Day 28 (1 to 4 weeks), Day 56 (5 to 8 weeks), and Day 84 (9 to 12 weeks)
Rate of response to therapy according to Outcome Measures in Rheumatology committee (OMERACT) and the Osteoarthritis Research Society International (OARSI)	By Day 28, Day 56, and Day 84	OMERACT and OARSI responder criteria are based on the symptomatic variables pain and function, or pain, function and patient's global assessment
WOMAC A1 responder rate based on percentage of patients with reduction in pain intensity of at least 30% and 50% at endpoint compared to baseline	Over 4 weeks (up to Day 28) and 12 weeks (up to Day 84) and at 1, 2, 3, 4, 6, 8, 10, and 12 weeks
Time to first WOMAC A1 response for ≥30% reduction in pain intensity	At 1, 2, 3, 4, 6, 8, 10, 12 weeks
Time to first WOMAC A1 response for 50% reduction in pain intensity	At 1, 2, 3, 4, 6, 8, 10, 12 weeks
Amount of rescue medication intake	Up to Day 84

Trial Locations

Locations (2)

Investigational Site Number 276001; 🇩🇪 Berlin, Germany

Investigational Site Number 276002; 🇩🇪 Luebeck, Germany