Study Assessing Pain Relief After Replacement of the Knee (SPARK)

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

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)

Study Overview

• Status: Terminated
• Conditions: Acute Postoperative Pain
• Intervention / Treatment: Drug: ATX-101; Drug: bupivacaine hydrochloride without epinephrine

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Prince of Wales Private Hospital
  • Queensland
    • Tugun, Queensland, Australia, 4224
      • John Flynn Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital / PARC Clinical Research
    • Adelaide, South Australia, Australia, 5000
      • St Andrew's Private Hospital
  • Victoria
    • Windsor, Victoria, Australia, 3181
      • The Avenue Private Hospital
• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K7
      • Durham Bone and Joint Specialists
    • London, Ontario, Canada, C9 124
      • London Health Sciences Centre - University Hospital
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Department of Trauma and Orthopaedic Surgery, Addenbrooke's Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Middlesex
    • Stanmore, Middlesex, United Kingdom, HA7 4LP
      • Royal National Orthopaedic Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham Elective Orthopaedic Service, Nottingham University Hospitals
  • Shropshire
    • Oswestry, Shropshire, United Kingdom, SY10 7AG
      • Robert Jones & Agnes Hunt Orthopaedic Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Chapel Allerton Hospital C/O The Leeds Teaching Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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.	NRS-R for pain intensity is an 11-item scale from 0 to10 where participants rank the level of pain intensity. The NRS scale goes from No Pain (0) to Worst Imaginable Pain (10).	from 30 minutes post-surgery through hour 168 (Day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subject Who Remain Opioid Free.	Opioid free is defined as no opioid rescue medication was recorded for the timepoint displayed and onwards.	Surgical Closure to Day 30
Total Post-surgical Use of Rescue Opioid Medications.	Total post-surgical use of rescue opioid medications (days).	Surgical Closure to Day 30, Opioid consumption is summarized descriptively every 24-hour period through Day 30
Time to First Rescue Opioid Medication.	Time to first postsurgical use of rescue opioid medication (days).	Surgical Closure to Day 30

Collaborators and Investigators

• Sponsor: Allay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): January 15, 2024

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: postoperative pain; bupivacaine; post-surgical pain total knee arthroplasty; total knee replacement ATX-101; bupivacaine implant
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Bupivacaine; Epinephrine
• Other Study ID Numbers: ATX-101-TKA-003

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes