Efficacy and Safety of G001 in Patients With Osteoarthritis (OA) of the Knee

Phase 2

Completed

Conditions: Osteoarthritis, Knee

Interventions: Drug: G001 Topical Gel
Drug: Vehicle

Registration Number: NCT05007808

Lead Sponsor: BUZZZ Pharmaceuticals Limited

Brief Summary: Phase 2 multicenter, double-blind, randomized, parallel-group, vehicle-controlled study to evaluate the efficacy, safety, and local tolerability of G001 topical gel compared to matching Vehicle topical gel in patients with symptomatic OA of the knee.

Each patient's participation is approximately 7 weeks (\~1 week screening, 4 weeks of treatment, and 2 weeks of post-treatment follow-up). Eligible patients with adequate OA pain in the index knee are randomized (1:1 allocation ratio) at the Baseline/Flare Visit 1.

Following screening, prior NSAID and/or acetaminophen use is discontinued to allow for washout and symptom flare. Patients are instructed to rate their worst daily and nightly pain in their daily diary, as well as to document all study drug applications and any rescue medication (acetaminophen) use for breakthrough pain. Acetaminophen may be used as rescue medication only, except within 12 hours prior to the Baseline Visit and within 12 hours prior to any post-baseline efficacy assessments (Weeks 2, 4, and 5). Patients are instructed to return to the clinic 3 to 7 days after the last study drug application for Flare Visit 2, and within approximately 2 weeks after the last study drug application for end-of-study evaluations.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 210

Inclusion Criteria

Documented diagnosis of OA of the knee, meeting American College of Rheumatology (ACR) criteria for classification of idiopathic (primary) OA for at least 6 months prior to Screening
Radiologic evidence of OA of the knee of grade 2 (mild) or grade 3 (moderate) according to Kellgren and Lawrence Radiographic Grading
Worst daily pain (within 24 hours prior to Screening and Baseline) in the index knee between 4 and 8 on the 11-point pain NRS
On stable analgesic therapy

At Baseline:

Development of a flare of pain following washout of stable analgesic (NSAID and/or acetaminophen) therapy

Exclusion Criteria

Radiologic evidence of severe OA of the knee (Kellgren and Lawrence grade 4)
Secondary OA of the index knee
Any other arthritis, included but not limited to rheumatoid arthritis, psoriatic arthritis, etc.
History of pseudo-gout or inflammatory flare-ups
History of severe neurological conditions
Any other chronic pain conditions (e.g., back pain) or disabling conditions affecting the joints
Patients who are non-ambulatory or require the use of crutches or a walker, or started using a cane within 30 days prior to Screening
Any history of major surgery to the index knee, minor knee surgery, or injury to the index knee within 1 year prior to Screening
Knee arthroscopy (index knee) within 3 months prior to Screening
Planned or candidate for knee replacement or knee reconstruction surgery
Received intra-articular viscosupplementation/hyaluronate, joint lavage, or other invasive therapies to the index knee in the past 90 days
Treatment with or need for any of the following: (1) oral or intramuscular corticosteroids within the past 90 days; (2) intra-articular corticosteroid injection into the index knee within the past 90 days, or into any other joint within the past 30 days; (3) current use of topical corticosteroids on the index knee
Prior stable therapy with an opioid analgesic, or anticipated need for opioid analgesic use during the study
Use of sedative hypnotic medication, antidepressants with known analgesic effect, antipsychotics, antiepileptics, and anti-Parkinson drugs within the past 14 days
Regular use of medication for headaches
Anticipated use of any oral or topical NSAID (apart from the study drug) during the study
Known sensitivity to the study drug (or any of its ingredients), or NSAIDs, or presence of contraindications, warnings, or precautions

At Baseline:

Worst daily pain (within the past 24 hours) in the contralateral knee assessed as >2 on the 11-point pain NRS scale
Non-compliance with the daily diary requirement during the Screening period.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G001 Topical Gel	G001 Topical Gel	G001 Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks.
Vehicle Topical Gel	Vehicle	Vehicle Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in WOMAC Pain Subscale Score at Week 4/EOT	Week 4	Changes from Baseline in WOMAC Pain Subscale Score (5-item scale, score range 0-20, with higher scores indicating worse outcome)

Secondary Outcome Measures

Name	Time	Method
Worst Daytime Pain Severity Scores (11-point Pain NRS), Based on Daily Diary Recordings	Week 4	Changes from Baseline to Week 4 in Worst Daytime Pain Severity Scores on a 0-10 scale, with higher scores indicating worse outcome
Worst Nighttime Pain Severity Score (11-point NRS), Based on Daily Diary Recordings	Week 4	Changes from Baseline to Week 4 in Worst Nighttime Pain Severity Scores recorded on a 0-10 scale, with higher scores indicating worse outcome
Percent Reduction From Baseline in Worst Daytime Pain	Week 4	Percentage of Patients Achieving ≥ 20%, ≥ 30%, and ≥ 50% Reduction from Baseline in Worst Daytime Pain at Week 4/EOT
Percent Reduction From Baseline in Worst Nighttime Pain	Week 4	Percentage of Patients Achieving ≥ 20%, ≥ 30%, and ≥ 50% Reduction from Baseline in Worst Nighttime Pain at Week 4/EOT
Change From Baseline in WOMAC Physical Function Subscale Score at Week 4/EOT	Week 4	WOMAC Physical Function Subscale (17-item, score range 0-68, with higher scores indicating worse outcome)
Change From Baseline in WOMAC Total Score at Week 4/EOT	Week 4	WOMAC Osteoarthritis Index Total score (24-item, score range 0-96, with higher scores indicating worse outcome)
Change From Baseline in WOMAC Stiffness Subscale Score at Week 4/EOT	Week 4	WOMAC Stiffness Subscale (2-item, range of scores 0-8, with higher scores indicating worse outcome)
Change From Baseline in WOMAC Total and Subscale Scores at Week 2	Week 2	Change from Baseline to Week 2 in: WOMAC Osteoarthritis Index Total score (24-item, score range 0-96, with higher scores indicating worse outcome) WOMAC Pain Subscale score (5-item, score range 0-20, with higher scores indicating worse pain) WOMAC Stiffness Subscale score (2-item, score range 0-8, with higher scores indicating worse stiffness) WOMAC Physical Function Subscale score (17-item, score range 0-68, with higher scores indicating worse physical function)
Change From Week 4 to Week 5 in WOMAC Total and Subscale Scores	Week 4 to Week 5	Change from Week 4/EOT to Week 5/Flare Visit 2 (FV2) in: WOMAC Osteoarthritis Index Total score (24-item, score range 0-96, with higher scores indicating worse outcome) WOMAC Pain Subscale score (5-item, score range 0-20, with higher scores indicating worse pain) WOMAC Stiffness Subscale score (2-item, score range 0-8, with higher scores indicating worse stiffness) WOMAC Physical Function Subscale score (17-item, score range 0-68, with higher scores indicating worse physical function)
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Over Time	Weeks 2, 4 and 5	PGA of Disease Activity (DA) was assessed on a 5-point Likert scale (0 = very good; 1 = good; 2 = fair; 3 = poor; and 4 = very poor), with higher scores indicating worse outcome. Change from Baseline in PGA of disease activity scores was calculated and the response was classified into 3 categories according to the following rules: Improved - defined as either of the following: * For baseline Grade ≥ 2: a reduction of ≥ 2 grades from baseline * For baseline Grade = 1: a change in grade from 1 to 0 Worsened - defined as either of the following: * For baseline Grade ≤ 2: an increase of ≥ 2 grades from baseline * For baseline Grade = 3: a change in grade from 3 to 4 No Change - defined as neither Improved nor Worsened
Change From Baseline in Investigator Global Assessment (IGA) of Disease Activity Over Time	Weeks 2, 4 and 5	IGA of Disease Activity (DA) was assessed on a 5-point Likert scale (0 = very good; 1 = good; 2 = fair; 3 = poor; and 4 = very poor), with higher scores indicating worse outcome. Change from Baseline in IGA of disease activity scores was calculated and the response was classified into 3 categories according to the following rules: Improved - defined as either of the following: * For baseline Grade ≥ 2: a reduction of ≥ 2 grades from baseline * For baseline Grade = 1: a change in grade from 1 to 0 Worsened - defined as either of the following: * For baseline Grade ≤ 2: an increase of ≥ 2 grades from baseline * For baseline Grade = 3: a change in grade from 3 to 4 No Change - defined as neither Improved nor Worsened
PGA of Overall Treatment Benefit (OTB)	Weeks 2 and 4	PGA of overall treatment benefit was completed using a 5-point Likert scale (0 = very good; 1 = good; 2 = fair; 3 = poor; and 4 = very poor) after 2 and 4 weeks of treatment, with higher scores indicating worse outcome.
IGA of Overall Treatment Benefit (OTB)	Weeks 2 and 4	IGA of overall treatment benefit was completed using a 5-point Likert scale (0 = very good; 1 = good; 2 = fair; 3 = poor; and 4 = very poor) after 2 and 4 weeks of treatment, with higher scores indicating worse outcome.
Rescue Medication Use	5 weeks	Only acetaminophen was permitted as rescue medication (up to 500 mg per dose and 2000 mg/day to manage breakthrough pain). No rescue medication use was allowed within 12 hours before an efficacy assessment.
Number of Rescue Medication Doses	5 weeks	Only acetaminophen was permitted as rescue medication (up to 500 mg per dose and 2000 mg/day to manage breakthrough pain). No rescue medication use was allowed within 12 hours before an efficacy assessment.

Trial Locations

Locations (10): Alpha Recherche Clinique (2)
🇨🇦
Quebec City, Canada
Recherche GCP Research
🇨🇦
Montréal, Canada
Medicor Research Inc.
🇨🇦
Sudbury, Canada
Manna Research
🇨🇦
Lévis, Canada
Aggarwal and Associates Limited
🇨🇦
Brampton, Canada
Centre de Recherche Saint-Louis
🇨🇦
Quebec City, Canada
Alpha recherche Clinique (1)
🇨🇦
Quebec City, Canada
Recherche Clinique Sigma Inc.
🇨🇦
Quebec City, Canada
G.R.M.O. (Groupe de Recherche en Maladie Osseuses) Inc.
🇨🇦
Quebec City, Canada
Canadian Phase Onward Inc.
🇨🇦
Toronto, Canada