Clinical trial NCT05007808: Efficacy and Safety of G001 in Patients With Osteoarthritis (OA) of the Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: osteoarthritis
knee
topical therapy
pain
Lead sponsor: BUZZZ Pharmaceuticals Limited
Sponsor class: INDUSTRY
Collaborators: name: Veristat, Inc.
First posted: 2021-08-16
Enrollment: 210
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in WOMAC Pain Subscale Score at Week 4/EOT
timeFrame: Week 4
Secondary outcomes:
measure: Worst Daytime Pain Severity Scores (11-point Pain NRS), Based on Daily Diary Recordings
timeFrame: Week 4
measure: Worst Nighttime Pain Severity Score (11-point NRS), Based on Daily Diary Recordings
timeFrame: Week 4
measure: Percent Reduction From Baseline in Worst Daytime Pain
timeFrame: Week 4
measure: Percent Reduction From Baseline in Worst Nighttime Pain
timeFrame: Week 4
measure: Change From Baseline in WOMAC Physical Function Subscale Score at Week 4/EOT
timeFrame: Week 4
measure: Change From Baseline in WOMAC Total Score at Week 4/EOT
timeFrame: Week 4
measure: Change From Baseline in WOMAC Stiffness Subscale Score at Week 4/EOT
timeFrame: Week 4
measure: Change From Baseline in WOMAC Total and Subscale Scores at Week 2
timeFrame: Week 2
measure: Change From Week 4 to Week 5 in WOMAC Total and Subscale Scores
timeFrame: Week 4 to Week 5
measure: Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Over Time
timeFrame: Weeks 2, 4 and 5
measure: Change From Baseline in Investigator Global Assessment (IGA) of Disease Activity Over Time
timeFrame: Weeks 2, 4 and 5
measure: PGA of Overall Treatment Benefit (OTB)
timeFrame: Weeks 2 and 4
measure: IGA of Overall Treatment Benefit (OTB)
timeFrame: Weeks 2 and 4
measure: Rescue Medication Use
timeFrame: 5 weeks
measure: Number of Rescue Medication Doses
timeFrame: 5 weeks
Other outcomes:
measure: Number of Participants With AEs, Study Drug-related AEs, Serious AEs, and AEs Leading to Study Drug Discontinuation
timeFrame: 6 weeks
measure: Frequency and Severity of Application Site AEs
timeFrame: 6 weeks
measure: Skin Irritation Test Scores (Berger/Bowman Scoring Scale)
timeFrame: Weeks 2, 4, and 6
measure: ECG Abnormalities in QT, QTc, QRS, or PR Intervals
timeFrame: 4 weeks
measure: Changes From Baseline in Safety Laboratory Test Results
timeFrame: 6 weeks
measure: Changes in Vital Signs Measurements
timeFrame: 6 weeks
measure: Changes in Physical Examination
timeFrame: 6 weeks
Locations:
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
city: Lévis
country: Canada
facility: Manna Research
city: Montréal
country: Canada
facility: Recherche GCP Research
city: Quebec City
country: Canada
facility: Alpha recherche Clinique (1)
city: Quebec City
country: Canada
facility: Alpha Recherche Clinique (2)
city: Quebec City
country: Canada
facility: Centre de Recherche Saint-Louis
city: Quebec City
country: Canada
facility: G.R.M.O. (Groupe de Recherche en Maladie Osseuses) Inc.
city: Quebec City
country: Canada
facility: Recherche Clinique Sigma Inc.
city: Sudbury
country: Canada
facility: Medicor Research Inc.
city: Toronto
country: Canada
facility: Canadian Phase Onward Inc.
Study officials:
affiliation: Buzzz Pharma
name: Deirdre O'Keeffe, PhD
role: STUDY_DIRECTOR
References: