Study Assessing Pain Relief After Replacement of the Knee

NCT06799845 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: ATX-101-TKA-004
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Total Knee Arthroplasty (Postoperative Pain)

Keywords

postoperative pain; post-surgical pain total knee arthroplasty; bupivacaine; bupivacaine implant; total knee replacement; ATX101; TKA; post-operative pain; postsurgical pain; post-surgical pain; postsurgical pain total knee arthroplasty

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• AUC for the NRS-R of pain intensity

  30 minutes through 336 hours (Day 15) compared to placebo

• AUC for the NRS-R of pain intensity

  from 30 minutes through 504 hours (Day 22) compared to placebo

• 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

  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

  at Day 15 compared to placebo

Study Arms (3)

ATX101

EXPERIMENTAL

Drug: ATX101

saline placebo

PLACEBO COMPARATOR

Drug: saline placebo

bupivacaine hydrochloride

ACTIVE COMPARATOR

Drug: bupivacaine hydrochloride

Interventions

ATX101 DRUG

ATX101 bupivacaine implants, total of 1,500 mg into the surgical site

ATX101

bupivacaine hydrochloride DRUG

bupivacaine hydrochloride 0.25% without epinephrine/adrenaline, total 125 mg in 50 mL via local periarticular infiltration

bupivacaine hydrochloride

saline placebo DRUG

normal saline (0.9%) sodium chloride, total volume of up to 17 mL via local periarticular infiltration

saline placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Allay Therapeutics, Inc.: lead

Study Sites (11)

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

Location

Atlanta Centre for Medical Research

Atlanta, Georgia, 30331, United States

Location

NextStage Clinical Research

Wichita, Kansas, 67214, United States

Location

Chesapeake Research Group, LLC

Pasadena, Maryland, 21122, United States

Location

First Surgical Hospital

Bellaire, Texas, 77401, United States

Location

Legent Orthopedic Hospital

Carrollton, Texas, 75006, United States

Location

Memorial Hermann Village

Houston, Texas, 77043, United States

Location

Endeavor Clinical Trials, LLC

San Antonio, Texas, 78240, United States

Location

NextStage Clinical Research

San Antonio, Texas, 78258, United States

Location

JBR Clinical Research, LLC

Salt Lake City, Utah, 84107, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Bupivacaine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• David Hewitt, MD

  Allay Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: surgical staff and pharmacist dispensing assigned treatment will not be blinded to the trial treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: January 29, 2025
• Study Start: February 3, 2025
• Primary Completion: October 3, 2025
• Study Completion: October 3, 2025
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)