Study Assessing Pain Relief after Replacement of the Knee (SPARK)
Research type
Research Study
Full title
A Phase 2B, Randomized, Double Blind, Active Comparator, Multicenter, Safety, and Efficacy Trial of ATX 101 in Subjects Undergoing Total Knee Arthroplasty (SPARK)
IRAS ID
1006134
Contact name
Sharon Hall
Contact email
Sponsor organisation
Allay Therapeutics Inc.
Clinicaltrials.gov Identifier
Research summary
Research Summary
This study is for people who are having knee replacement surgery.
The main aims of the study are to:
1. see how well two different amounts (dose) of ATX-101 placed in the knee to control pain in the weeks after knee replacement surgery compares to injections of the same medicine injected around the tissues or the nerves in the knee
2. test the safety and if people in the study have side effects.
3. decide what dose of ATX-101 works best for pain relief after knee surgery, based on point 1 above
4. compare the amounts of opioids people participating in the study take over a one-month period
The test drug, ATX-101 is a medicine in a wafer that is placed in the body during surgery (implant) that the dissolves over time (bioabsorbable) to release the medicine. ATX-101 is made to provide pain relief after knee replacement surgery. The active ingredient in ATX-101 is bupivacaine hydrochloride. Each ATX-101 wafer contains 500 mg of bupivacaine.
Bupivacaine is a local anaesthetic, a pain numbing medication, which was discovered in 1957 and is on the World Health Organization's List of Essential Medicines. These are considered the most effective and safe medicines needed in a health system.
People who participate in this study will be randomly assigned (by chance) to get one of the treatments and they will not know what treatment they will receive. All research staff apart from the team doing the knee surgery, will also not know what treatment each person in the study has been given.
The trial has two parts. People will only participate in either Part A or Part B, but not both.
People in Part A will get either: one of two doses of ATX-101 (1000mg or 1500mg) or bupivacaine injection. People in Part B of the study will get ATX-101 of the dose that will be decided after the results from Part A have been reviewed or bupivacaine injection. The study treatment will be placed in the knee during the surgery.Summary of Results
In Part A, ATX-101 appears to be generally safe and well tolerated. No new or unexpected events were observed. There were no signs or symptoms of local anesthetic systemic toxicity. An assessment of wound healing did not show a higher incidence in the ATX-101 group. All cardiac abnormalities that were identified were considered unlikely or not related to the investigational product. The efficacy associated with the combined ATX-101 group and the 1,500 mg dose group alone demonstrated similar efficacy versus standard of care bupivacaine over the first 24 hours and superiority over standard of care bupivacaine in the two weeks following TKA. Pharmacokinetic analyses demonstrated that ATX-101 extended controlled release for approximately 3 weeks with the 1500 mg dose providing higher exposure than bupivacaine and the ATX-101 1000 mg dose. Interim analysis provided support for determination of the dose, sample size, and duration of the primary endpoint for the design of Part B of the study. The safety profile, including the PK profile and cardiovascular monitoring results, as well as the efficacy results from Part A support moving forward with the 1,500 mg dose in further studies, as well as reduced inpatient observation/monitoring. Development of ATX-101 will continue with the 1,500 mg dose in a new phase 2B study
REC name
South Central - Oxford C Research Ethics Committee
REC reference
22/SC/0385
Date of REC Opinion
13 Dec 2022
REC opinion
Further Information Favourable Opinion