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

Phase 2 Multicenter, Double-blind, Randomized, Parallel-Group, Vehicle-Controlled Study to Evaluate the Efficacy, Safety, and Local Tolerability of G001 in Patients With Osteoarthritis (OA) of the Knee

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: G001 Topical Gel; Drug: Vehicle

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Heather M Karabaich; Phone Number: 508-306-6352; Email: heather.karabaich@veristat.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G001 Topical Gel; G001 Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks.	Drug: G001 Topical Gel; Non-steroidal anti-inflammatory drug for topical administration
Placebo Comparator: Vehicle Topical Gel; Vehicle Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks.	Drug: Vehicle; Vehicle Gel for topical administration

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worst Daytime Pain Severity Scores (11-point Pain NRS), Based on Daily Diary Recordings	Changes from Baseline to Week 4 in Worst Daytime Pain Severity Scores on a 0-10 scale, with higher scores indicating worse outcome	Week 4
Worst Nighttime Pain Severity Score (11-point NRS), Based on Daily Diary Recordings	Changes from Baseline to Week 4 in Worst Nighttime Pain Severity Scores recorded on a 0-10 scale, with higher scores indicating worse outcome	Week 4
Percent Reduction From Baseline in Worst Daytime Pain	Percentage of Patients Achieving ≥ 20%, ≥ 30%, and ≥ 50% Reduction from Baseline in Worst Daytime Pain at Week 4/EOT	Week 4
Percent Reduction From Baseline in Worst Nighttime Pain	Percentage of Patients Achieving ≥ 20%, ≥ 30%, and ≥ 50% Reduction from Baseline in Worst Nighttime Pain at Week 4/EOT	Week 4
Change From Baseline in WOMAC Physical Function Subscale Score at Week 4/EOT	WOMAC Physical Function Subscale (17-item, score range 0-68, with higher scores indicating worse outcome)	Week 4
Change From Baseline in WOMAC Total Score at Week 4/EOT	WOMAC Osteoarthritis Index Total score (24-item, score range 0-96, with higher scores indicating worse outcome)	Week 4
Change From Baseline in WOMAC Stiffness Subscale Score at Week 4/EOT	WOMAC Stiffness Subscale (2-item, range of scores 0-8, with higher scores indicating worse outcome)	Week 4
Change From Baseline in WOMAC Total and Subscale Scores at 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)	Week 2
Change From Week 4 to Week 5 in WOMAC Total and Subscale Scores	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)	Week 4 to Week 5
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Over Time	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	Weeks 2, 4 and 5
Change From Baseline in Investigator Global Assessment (IGA) of Disease Activity Over Time	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	Weeks 2, 4 and 5
PGA of Overall Treatment Benefit (OTB)	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.	Weeks 2 and 4
IGA of Overall Treatment Benefit (OTB)	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.	Weeks 2 and 4
Rescue Medication Use	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.	5 weeks
Number of Rescue Medication Doses	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.	5 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs, Study Drug-related AEs, Serious AEs, and AEs Leading to Study Drug Discontinuation	Number and percentage of participants with adverse events (AEs), study drug-related AEs, serious AEs, and AEs leading to study drug discontinuation	6 weeks
Frequency and Severity of Application Site AEs	Number and percentage of participants with application site AEs	6 weeks
Skin Irritation Test Scores (Berger/Bowman Scoring Scale)	The Numerical Total Score is the sum of the Dermal Response score (from 0=No evidence of irritation to 7=Strong reaction spreading beyond the application site) and the numeric equivalent of Other Effects score (from 0=Slightly glazed appearance to 3=Small petechial erosions and/or scabs). The Numerical Total Score range is from 0 to 10, with higher scores indicating worse outcome/skin irritation.	Weeks 2, 4, and 6
ECG Abnormalities in QT, QTc, QRS, or PR Intervals	Number and percentage of participants with clinically significant (CS) abnormal results in QT, QTc, QRS, or PR intervals at Week 4/EOT	4 weeks
Changes From Baseline in Safety Laboratory Test Results	Mean changes (descriptive) and shifts from normal baseline to laboratory values outside reference ranges	6 weeks
Changes in Vital Signs Measurements	Mean changes (descriptive) from baseline	6 weeks
Changes in Physical Examination	Number and percentage of participants with clinically significant abnormal findings	6 weeks

Collaborators and Investigators

• Sponsor: BUZZZ Pharmaceuticals Limited
• Collaborators: Veristat, Inc.
• Investigators: Study Director: Deirdre O'Keeffe, PhD, Buzzz Pharma

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Actual): January 4, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: osteoarthritis; pain; knee; topical therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 2020-G001-P2

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: Yes
• Studies a U.S. FDA-regulated device product: No