Clinical trial NCT03978208: Efficacy and Safety of ATB-346 Versus Placebo in Osteoarthritis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis
Keywords: Knee
WOMAC
NSAID
Pain
Lead sponsor: Antibe Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Veristat, Inc.
First posted: 2019-06-07
Enrollment: 381
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 5-item pain intensity measure
timeFrame: Previous 48 hours
Secondary outcomes:
measure: 2-item stiffness intensity measure
timeFrame: Previous 48 hours
measure: 17-item difficulty performing daily activities measure
timeFrame: Previous 48 hours
measure: Measurement of whole blood cyclo-oxygenase activity
timeFrame: After 1, 4 and 14 days of treatment dosing.
measure: Number of patients with genetic variations in the drug modifying enzyme CYP2C9 that may alter the metabolism of ATB-346 will be investigated.
timeFrame: Samples will be retained through study completion and analyzed within 1 year of study initiation.
measure: Number of participants with treatment-related adverse events
timeFrame: Pre-study and days 4, 14 and 24.
Other outcomes:
Locations:
city: Mission
country: Canada
facility: Viable Clinical Research Corp
state: British Columbia
city: Surrey
country: Canada
facility: Ocean West Research Clinic
state: British Columbia
city: Vancouver
country: Canada
facility: James K. Lai MD Inc
state: British Columbia
city: Victoria
country: Canada
facility: Dr. MB Jones Inc
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research Inc.
state: Nova Scotia
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
state: Ontario
city: Burlington
country: Canada
facility: Manna Research (Burlington North)
state: Ontario
city: Etobicoke
country: Canada
facility: Etobicoke Medical Centre
state: Ontario
city: Guelph
country: Canada
facility: Dawson Clinical Research
state: Ontario
city: Hamilton
country: Canada
facility: Dr. Allen Greenspoon Medicine Professional Corporation
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Medical Research Group
state: Ontario
city: London
country: Canada
facility: Milestone Research Inc.
state: Ontario
city: London
country: Canada
facility: KGK Science Inc
state: Ontario
city: Mississauga
country: Canada
facility: Malton Medical Clinic
state: Ontario
city: Newmarket
country: Canada
facility: SKDS Research Inc
state: Ontario
city: Oshawa
country: Canada
facility: King Street Medical Clinic
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Scarborough
country: Canada
facility: Viable Clinical Research Corp
state: Ontario
city: Stoney Creek
country: Canada
facility: Dr. Steven V. Zizzo Medicine Professional Corporation
state: Ontario
city: Stoney Creek
country: Canada
facility: Manna Research (Stoney Creek)
state: Ontario
city: Toronto
country: Canada
facility: Canadian Phase Onward Inc.
state: Ontario
city: Toronto
country: Canada
facility: LMC Clinical Research Inc
state: Ontario
city: Toronto
country: Canada
facility: Manna Research (Toronto)
state: Ontario
city: Windsor
country: Canada
facility: Dr. Sabeen Anwar Medicine Professional Corporation
state: Ontario
city: Windsor
country: Canada
facility: Clinical Research& Arthritis Centre
state: Ontario
city: Woodstock
country: Canada
facility: Devonshire Clinical Research Inc.
state: Ontario
city: Lévis
country: Canada
facility: Manna Research (Quebec)
state: Quebec
city: Mirabel
country: Canada
facility: Manna Research (Mirabel QC)
state: Quebec
city: Montréal
country: Canada
facility: Recherche GCP Research
state: Quebec
city: Montréal
country: Canada
facility: Centre Medical Acadie
state: Quebec
city: Pointe-Claire
country: Canada
facility: Manna Research (Montreal)
state: Quebec
city: Quebec City
country: Canada
facility: Diex Recherche Quebec Inc.
state: Quebec
city: Quebec City
country: Canada
facility: Centre de Recherche Saint-Louis
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc.
state: Quebec
city: Victoriaville
country: Canada
facility: Diex Recherche Victoriaville Inc.
state: Quebec
Study officials:
affiliation: Veristat
name: Deepen Patel, MD
role: STUDY_DIRECTOR
References: