Study Assessing Pain Relief After Replacement of the Knee (SPARK 2)

A Phase 2B, Randomized, Double Blind, Placebo and Active Comparator Controlled, Multicenter, Safety, and Efficacy Trial of ATX101 in Adults Undergoing Total Knee Arthroplasty

The goal of the ATX101-TKA-004 clinical trial aims to evaluate the efficacy and safety of ATX101 1,500 mg in participants undergoing primary unilateral total knee arthroplasty. The study will compare the effectiveness of ATX101 with a saline placebo and bupivacaine, an active comparator. Additionally, it will assess opioid consumption among participants receiving ATX101 versus those given the saline placebo and bupivacaine. The trial will also focus on the safety and tolerability of ATX101 in the participants.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty (Postoperative Pain)
• Intervention / Treatment: Drug: ATX101; Drug: saline placebo; Drug: bupivacaine hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, LLC
  • Florida
    • Tamarac, Florida, United States, 33321
      • Phoenix Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Centre for Medical Research
  • Kansas
    • Wichita, Kansas, United States, 67214
      • NextStage Clinical Research
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Surgical Hospital
    • Carrollton, Texas, United States, 75006
      • Legent Orthopedic Hospital
    • Houston, Texas, United States, 77043
      • Memorial Hermann Village
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Trials, LLC
    • San Antonio, Texas, United States, 78258
      • NextStage Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Primary indication of TKA is knee pain due to osteoarthritis or post-traumatic arthritis
• Scheduled to undergo primary unilateral TKA 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
• Capable, able, and willing to comply with all trial visits and procedures. Participant must also be able to use trial required e-diary and demonstrate completion compliance during the screening period
• English or Spanish speaking, willing, and capable of providing written informed consent

Key Exclusion Criteria:

• Has a planned concurrent surgical procedure (e.g. bilateral TKA) at the time of surgery or a planned surgical procedure before the last trial visit
• Has had any previous open surgery, (e.g., ORIF for fracture, osteotomy, arthroplasty, unicompartmental knee arthroplasty, or TKA), in the trial knee at any time in the past or arthroscopic surgery within 12 months. Has had any previous surgery 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
• Unable to abstain from opioid use for knee pain (including codeine) within 2 weeks (14 days) of surgery
• Has a Body Mass Index (BMI) ≥45 kg/m²
• Is unwilling or unable to discontinue use of medications or products that can impact pain control from the Screening Visit until the last trial visit (e.g. cannabidiol (CBD) oil, Kratom)
• 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 participant or confound the postsurgical assessments or might confound or interfere with the outcome of the trial
• Has received/used an investigational drug, product, or device for a clinical trial within 30 days of screening. COVID-19 vaccines (approved or under emergency use authorization locally) are permitted if the participant is not in a clinical trial for the vaccine
• Has a positive drug screen at the Screening Visit or on the day of surgery
• Has participated in an ATX101 clinical trial
• Pregnant, breastfeeding, or planning to become pregnant during the trial or before the last trial visit

Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: saline placebo	Drug: saline placebo; normal saline (0.9%) sodium chloride, total volume of up to 17 mL via local periarticular infiltration
Experimental: ATX101	Drug: ATX101; ATX101 bupivacaine implants, total of 1,500 mg into the surgical site
Active Comparator: bupivacaine hydrochloride	Drug: bupivacaine hydrochloride; bupivacaine hydrochloride 0.25% without epinephrine/adrenaline, total 125 mg in 50 mL via local periarticular infiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) for the Numerical 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 through 168 hours (Day 8) compared to placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total post-surgical consumption of opioid medications		from 30 minutes through 336 hours (Day 15) compared to placebo
AUC for the 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).	30 minutes through 336 hours (Day 15) compared to placebo
AUC for the 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 through 504 hours (Day 22) compared to placebo
AUC for the 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 through 336 hours (Day 15) compared to active comparator
Difference in NRS-A pain intensity scores during the Timed Up and Go (TUG) Test	The NRS with activity (NRS-A) for pain intensity is an 11-item scale from 0 to 10 where participants rank the level of pain intensity after an activity. The NRS scale goes from No Pain (0) to Worst Imaginable Pain (10).	at Day 15 compared to placebo

Collaborators and Investigators

• Sponsor: Allay Therapeutics, Inc.
• Investigators: Study Director: David Hewitt, MD, Allay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Actual): October 3, 2025
• Study Completion (Actual): October 3, 2025

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: total knee replacement; postoperative pain; bupivacaine; post-surgical pain total knee arthroplasty; bupivacaine implant; post-operative pain; post-surgical pain; TKA; postsurgical pain; ATX101; postsurgical pain total knee arthroplasty
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Bupivacaine
• Other Study ID Numbers: ATX-101-TKA-004

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.: No