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

Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03978208
• Other study ID #: ATB-346-P2B-DRF
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2019
• Est. completion date: December 29, 2019

Study information

• Verified date: July 2022
• Source: Antibe Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: December 29, 2019
• Est. primary completion date: December 29, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Drug:
• ATB-346 low dose
Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Other:
• Placebo
Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Drug:
• ATB-346 mid-dose
Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients
• ATB-346 standard dose
Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Locations

Country	Name	City	State
Canada	Aggarwal and Associates Limited	Brampton	Ontario
Canada	Manna Research (Burlington North)	Burlington	Ontario
Canada	Etobicoke Medical Centre	Etobicoke	Ontario
Canada	Dawson Clinical Research	Guelph	Ontario
Canada	True North Clinical Research Inc.	Halifax	Nova Scotia
Canada	Dr. Allen Greenspoon Medicine Professional Corporation	Hamilton	Ontario
Canada	Hamilton Medical Research Group	Hamilton	Ontario
Canada	Manna Research (Quebec)	Lévis	Quebec
Canada	KGK Science Inc	London	Ontario
Canada	Milestone Research Inc.	London	Ontario
Canada	Manna Research (Mirabel QC)	Mirabel	Quebec
Canada	Viable Clinical Research Corp	Mission	British Columbia
Canada	Malton Medical Clinic	Mississauga	Ontario
Canada	Centre Medical Acadie	Montréal	Quebec
Canada	Recherche GCP Research	Montréal	Quebec
Canada	SKDS Research Inc	Newmarket	Ontario
Canada	King Street Medical Clinic	Oshawa	Ontario
Canada	Manna Research (Montreal)	Pointe-Claire	Quebec
Canada	Centre de Recherche Saint-Louis	Quebec City	Quebec
Canada	Diex Recherche Quebec Inc.	Quebec City	Quebec
Canada	Bluewater Clinical Research Group Inc	Sarnia	Ontario
Canada	Viable Clinical Research Corp	Scarborough	Ontario
Canada	Diex Recherche Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Dr. Steven V. Zizzo Medicine Professional Corporation	Stoney Creek	Ontario
Canada	Manna Research (Stoney Creek)	Stoney Creek	Ontario
Canada	Ocean West Research Clinic	Surrey	British Columbia
Canada	Canadian Phase Onward Inc.	Toronto	Ontario
Canada	LMC Clinical Research Inc	Toronto	Ontario
Canada	Manna Research (Toronto)	Toronto	Ontario
Canada	James K. Lai MD Inc	Vancouver	British Columbia
Canada	Dr. MB Jones Inc	Victoria	British Columbia
Canada	Diex Recherche Victoriaville Inc.	Victoriaville	Quebec
Canada	Clinical Research& Arthritis Centre	Windsor	Ontario
Canada	Dr. Sabeen Anwar Medicine Professional Corporation	Windsor	Ontario
Canada	Devonshire Clinical Research Inc.	Woodstock	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Antibe Therapeutics Inc.	Veristat, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.