Study Assessing Pain Relief After Replacement of the Knee

Study Overview
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Brief Summary
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This is a Phase 2B randomized, double blind, active controlled, multi-center clinical trial to evaluate the safety and efficacy of ATX-101 in participants following total knee arthroplasty. The following is short title and acronym for the study: Study Assessing Pain Relief after Replacement of the Knee (SPARK)

Official Title
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A Phase 2B, Randomized, Double Blind, Active Comparator, Multicenter, Safety, and Efficacy Trial of ATX-101 in Subjects Undergoing Total Knee Arthroplasty

Conditions
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Acute Postoperative Pain

Intervention / Treatment
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* Drug: ATX-101
* Drug: ATX-101
* Drug: bupivacaine hydrochloride without epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary indication of total knee arthroplasty is knee pain due to osteoarthritis or post-traumatic arthritis. Scheduled to undergo primary unilateral total knee arthroplasty with a cemented prosthesis, without use of a surgical drain, and under bupivacaine spinal anesthesia (dextrose is permitted). American Society of Anesthesiology (ASA) Physical Classification System of class 1, 2 or 3. Exclusion Criteria: Has a planned concurrent surgical procedure. Has had any previous arthroplasty, unicompartmental knee arthroplasty or total knee arthroplasty in the study knee or previous arthroplasty, unicompartmental knee arthroplasty, or total knee arthroplasty in the contralateral knee within 6 months prior to screening. Has been administered any type of intra-articular injection within 3 months of surgery in the trial knee. Immunocompromised or has a known history of Hepatitis B, human immunodeficiency virus (HIV), or Hepatitis C. Routinely take opioid analgesics and are expected to require opioid analgesics in the postsurgical period that is not strictly related to the trial. Unable to abstain from opioid use for knee pain within 14 days of surgery. Has been administered systemic steroids within 14 days prior to surgery. Has been administered any local anesthetic within 5 days prior to the scheduled surgery. Screening electrocardiogram (ECG) with significant abnormalities associated with significant heart disease. Has a contraindication or a known suspected history of allergy, hypersensitivity or idiosyncratic reaction to trial medications. Has uncontrolled depression, anxiety, psychiatric, or neurological disorder that might interfere with trial study assessments. Has a medical condition or receiving medication such that, in the opinion of the investigator, participating in the trial would pose a health risk to the subject or might interfere with the study outcome. Has a known or suspected history of drug or alcohol abuse. A subject with a history of alcohol use disorder that has ≥10 years sobriety will be permitted. Has received/used an investigational drug, product, or device for a clinical trial within 30 days of screening. COVID-19 vaccines are permitted if the subject is not in a clinical trial for the vaccine. Has a Body Mass Index (BMI) ≥45 kg/m2.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 2B, randomized, double blind, active comparator multicenter trial in participants undergoing total knee arthroplasty.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATX-101 Dose A<br>ATX-101 Dose A | Drug: ATX-101<br>* ATX-101 (bupivacaine) implant, one-time administration into the surgical site<br>|
| Experimental: ATX-101 Dose B<br>ATX-101 Dose B | Drug: ATX-101<br>* ATX-101 (bupivacaine) implant, one-time administration into the surgical site<br>|
| Active Comparator: bupivacaine hydrochloride<br>bupivacaine hydrochloride without epinephrine via local infiltration and/or nerve block | Drug: bupivacaine hydrochloride without epinephrine<br>* bupivacaine hydrochloride (125 mg) without epinephrine via local infiltration and/or nerve block<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) for the Numeric Rating Scale at Rest (NRS-R) of pain intensity. |  | from 30 minutes post-surgery through hour 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) for the Numeric Rating Scale at Rest (NRS-R) of pain intensity. |  | from 30 Minutes post-surgery through Hour 168, Hour 240, and Hour 336 | 
| Percentage of subjects who remain opioid free. |  | from Hour 72 post-surgery through Day 30 | 
| Total post-surgical consumption of opioid medications. |  | from surgical closure through Day 30 | 
| Area under the curve for the Numeric Rating Scale at Rest (NRS-R) of pain intensity. |  | from surgical closure for each 24-hour period through Hour 336 | 
| Percentage of subject who remain opioid free. |  | Surgical Closure to Day 30 | 
| Total post-surgical use of rescue opioid medications. |  | Surgical Closure to Day 30 | 
| Time to first postsurgical use of rescue opioid medication. |  | Surgical Closure to Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative pain, post-surgical pain total knee arthroplasty, total knee replacement ATX-101, bupivacaine, bupivacaine implant