Efficacy and Safety of ATB-346 Versus Placebo in Osteoarthritis Patients

A Double-Blind, Placebo-Controlled, Phase 2B Study to Assess the Efficacy and Safety of a 14-Day Dosing Regimen of 3 Doses of ATB-346 Versus Placebo, Orally Administered Once Daily to Patients Diagnosed With Osteoarthritis of the Knee

The primary objective of this study is to evaluate the efficacy of a 14-day dosing regimen of ATB-346 at doses of 150 mg, 200 mg and 250 mg compared to placebo in reducing osteoarthritis knee pain as measured by changes in the post-treatment WOMAC subscale pain score relative to each patient's pretreatment baseline WOMAC assessment.Safety will be assessed via measurements of vital signs and clinical laboratory tests at baseline and at various time points during the study, patient monitoring, and by the documentation of adverse events.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: ATB-346 low dose; Drug: ATB-346 mid-dose; Drug: ATB-346 standard dose; Other: Placebo

Detailed Description

The primary objective of this study is to evaluate the efficacy of a 14-day dosing regimen of once daily administration of ATB-346 at doses of 150 mg, 200 mg and 250 mg compared to placebo in reducing osteoarthritis knee pain as measured by changes in the post-treatment WOMAC subscale pain score relative to each patient's pretreatment baseline WOMAC assessment.A total of 360 evaluable patients are planned in this study: 250 mg (n=120); 200 mg (n=120); 150 mg (n=60); placebo (n=60).

Safety will be assessed via measurements of vital signs and clinical laboratory tests at baseline and at various time points during the study, patient monitoring, and by the documentation of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Mission, British Columbia, Canada, V2V 1C6
      • Viable Clinical Research Corp
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Ocean West Research Clinic
    • Vancouver, British Columbia, Canada, V5Z 1K3
      • James K. Lai MD Inc
    • Victoria, British Columbia, Canada, V8V 4A1
      • Dr. MB Jones Inc
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1M7
      • True North Clinical Research Inc.
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • Burlington, Ontario, Canada, L7M 4Y1
      • Manna Research (Burlington North)
    • Etobicoke, Ontario, Canada, M8Z 5W4
      • Etobicoke Medical Centre
    • Guelph, Ontario, Canada, N1H 1B1
      • Dawson Clinical Research
    • Hamilton, Ontario, Canada, L8L 5G8
      • Dr. Allen Greenspoon Medicine Professional Corporation
    • Hamilton, Ontario, Canada, L8M 1K7
      • Hamilton Medical Research Group
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research Inc.
    • London, Ontario, Canada, N6A 5R8
      • KGK Science Inc
    • Mississauga, Ontario, Canada, L4V 1P1
      • Malton Medical Clinic
    • Newmarket, Ontario, Canada, L3Y 5G8
      • SKDS Research Inc
    • Oshawa, Ontario, Canada, L1H 1G6
      • King Street Medical Clinic
    • Sarnia, Ontario, Canada, N7t 4X3
      • Bluewater Clinical Research Group Inc
    • Scarborough, Ontario, Canada, M1P 2T7
      • Viable Clinical Research Corp
    • Stoney Creek, Ontario, Canada, L8J 0B6
      • Dr. Steven V. Zizzo Medicine Professional Corporation
    • Stoney Creek, Ontario, Canada, L8J 3W2
      • Manna Research (Stoney Creek)
    • Toronto, Ontario, Canada, M3J 0K2
      • Canadian Phase Onward Inc.
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Clinical Research Inc
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research (Toronto)
    • Windsor, Ontario, Canada, N8X 1T3
      • Dr. Sabeen Anwar Medicine Professional Corporation
    • Windsor, Ontario, Canada, N8X 2C9
      • Clinical Research& Arthritis Centre
    • Woodstock, Ontario, Canada, N4S 5P5
      • Devonshire Clinical Research Inc.
  • Quebec
    • Lévis, Quebec, Canada, G6W 0M5
      • Manna Research (Quebec)
    • Mirabel, Quebec, Canada, J7J 2K8
      • Manna Research (Mirabel QC)
    • Montréal, Quebec, Canada, H1M 1B1
      • Recherche GCP Research
    • Montréal, Quebec, Canada, H4N 2W2
      • Centre Medical Acadie
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • Manna Research (Montreal)
    • Quebec City, Quebec, Canada, G1N 4V3
      • Diex Recherche Quebec Inc.
    • Quebec City, Quebec, Canada, G1W 4R4
      • Centre de recherche Saint-Louis
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke Inc.
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Diex Recherche Victoriaville Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis greater than 2 years duration requiring the use of regular therapies, e.g. oral or topical anti-inflammatories, acetaminophen, topical capsaicin
• Between the ages of 40 to 75
• BMI ≤40
• Patients must be unlikely to procreate or agree to the use of acceptable contraceptive regimens from first drug administration , during the study, and for at least 30 days after the last dose
• Patients must not have used aspirin or naproxen-containing medications for 7 days prior to study entry
• Patients must not have used any anti-inflammatory medications or acetaminophen for 5 days prior to study entry
• Patients must show a ≥10-point increase in WOMAC Visual Analog Score between their screening visit and baseline study entry visit

Exclusion Criteria:

• Females who are pregnant or breastfeeding
• Seated and resting pulse rate less than 50 beats per minute (bpm) or more than 100 bpm at screening
• Seated and resting blood pressure below 100/60 mmHg or higher than 140/90 mmHg at screening
• History of significant hypersensitivity to naproxen, other non-steroidal anti-inflammatory agents, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Patients with a history of GI bleeding or ulceration
• Patients refractory to NSAIDs
• Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or know to potentiate or predispose patients to undesired effects
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease as determined by the investigator
• Suicidal tendency, history of/or disposition to seizures, state of confusion
• History of hepatic disease
• Maintenance therapy with any drug, including gastroprotective agents such as proton pump inhibitors, H2 receptor antagonists, sucralfate, etc., or significant history of drug dependency or alcohol abuse (>3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the previous 30 days before Day 1 of this study
• Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort) in the previous 30 days before Day 1 of this study
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive H. Pylori Urea Breathe Test
• Positive urine screening of alcohol and/or drugs of abuse at the screening visit
• Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAg) or anti-Hepatitis C Virus (HCV) tests
• Females who are pregnant according to a positive serum pregnancy test
• Patients who took an Investigational Product (in another clinical trial) in the previous 30 days before Day 1 of this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo Comparator; ATB-346 150 mg overencapsulated tablet taken by mouth once daily for 14 days	Drug: ATB-346 low dose; Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients; Other Names: Active comparator
Active Comparator: ATB-346 mid-dose; ATB-346 200 mg overencapsulated tablet taken by mouth once daily for 14 days	Drug: ATB-346 mid-dose; Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients; Other Names: Active comparator
Active Comparator: ATB-346 standard dose; ATB-346 250 mg overencapsulated tablet taken by mouth once daily for 14 days	Drug: ATB-346 standard dose; Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients; Other Names: Active comparator
Placebo Comparator: Active Comparator; Overencapsulated placebo tablet taken by mouth once daily for 14 days	Other: Placebo; Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients; Other Names: Non-active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-item pain intensity measure	Self reported pain intensity over the past 48 hours. Each item is scored 0-10 (0 = no pain; 10 = pain as bad as can be), yielding a total between 0 and 50	Previous 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-item stiffness intensity measure	Self reported pain intensity over the past 48 hours. Each item is scored 0-10 (0 = no pain; 10 = pain as bad as can be), yielding a total between 0 and 20	Previous 48 hours
17-item difficulty performing daily activities measure	Self reported pain intensity over the past 48 hours. Each item is scored 0-10 (0 = no pain; 10 = pain as bad as can be), yielding a total between 0 and 170	Previous 48 hours
Measurement of whole blood cyclo-oxygenase activity	Thromboxane B2 (TXB2) blood levels (pg/mL) will be measured after 1, 4 and 14 days of treatment. samples taken on days 1, 4 and 14. Decreases (measured in pg/mL) in the blood levels of thromboxane B2 are a direct measure of the effect of treatment on cyclo-oxygenase activity and the reduced production of this inflammatory mediator, i.e., thromboxane B2.	After 1, 4 and 14 days of treatment dosing.
Number of patients with genetic variations in the drug modifying enzyme CYP2C9 that may alter the metabolism of ATB-346 will be investigated.	CYP2C9 isoforms will be measured in one blood sample taken prior to study drug dosing.	Samples will be retained through study completion and analyzed within 1 year of study initiation.
Number of participants with treatment-related adverse events	The safety of ATB-346 will be monitored via on study and two week post study physician and clinical laboratory assessments.	Pre-study and days 4, 14 and 24.

Collaborators and Investigators

• Sponsor: Antibe Therapeutics Inc.
• Collaborators: Veristat, Inc.
• Investigators: Study Director: Deepen Patel, MD, Veristat

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2019
• Primary Completion (Actual): December 29, 2019
• Study Completion (Actual): December 29, 2019

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: June 4, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Pain; Knee; WOMAC; NSAID
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: ATB-346-P2B-DRF

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