Total Knee Arthroplasty (Postoperative Pain)Phase 2SPARK2NCT06799845
Phase 2B Study Assessing Pain Relief After Replacement of the Knee
A Phase 2 study testing ATX101 and bupivacaine hydrochloride in people with Total Knee Arthroplasty (Postoperative Pain), run by Allay Therapeutics, Inc. at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Total Knee Arthroplasty (Postoperative Pain)
- What is being tested?
- ATX101 and bupivacaine hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 226 participants
- Where
- 11 sitesUnited States
- Study dates
- 3 Feb 2025to 3 Oct 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Atlanta Centre for Medical Research
Atlanta, Georgia, 30331
First Surgical Hospital
Bellaire, Texas, 77401
Legent Orthopedic Hospital
Carrollton, Texas, 75006
Memorial Hermann Village
Houston, Texas, 77043
Woodland International Research Group, LLC
Little Rock, Arkansas, 72211
Chesapeake Research Group, LLC
Pasadena, Maryland, 21122
JBR Clinical Research, LLC
Salt Lake City, Utah, 84107
Endeavor Clinical Trials, LLC
San Antonio, Texas, 78240
NextStage Clinical Research
San Antonio, Texas, 78258
Phoenix Clinical Research
Tamarac, Florida, 33321
NextStage Clinical Research
Wichita, Kansas, 67214
About this study
Official title: 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.
- Being tested
- ATX101, bupivacaine hydrochloride, saline placebo
- 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
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATX101Drug
ATX101 bupivacaine implants, total of 1,500 mg into the surgical site
bupivacaine hydrochlorideDrug
bupivacaine hydrochloride 0.25% without epinephrine/adrenaline, total 125 mg in 50 mL via local periarticular infiltration
saline placeboDrug
normal saline (0.9%) sodium chloride, total volume of up to 17 mL via local periarticular infiltration
| Study group | Role | What they receive |
|---|---|---|
| ATX101 | Experimental | Not described Receives: Drug: ATX101 |
| saline placebo | Placebo comparator | Not described Receives: Drug: saline placebo |
| bupivacaine hydrochloride | Active comparator | Not described Receives: Drug: bupivacaine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain Intensity From 30 Minutes Through 168 Hours (Day 8) Compared to Placebo
Numeric Rating Scale at Rest (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).
Measured: from 30 minutes through 168 hours (Day 8)
Secondary outcomes (5)
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
Numeric Rating Scale at Rest (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).
Measured: From 30 minutes through 336 hours (Day 15)
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 504 Hours (Day 22) Compared to Placebo
Numeric Rating Scale at Rest (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).
Measured: From 30 minutes through 504 hours (Day 22)
Total Post-surgical Consumption of Opioid Medications From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
Total post-surgical consumption of rescue opioid medications in morphine milligrams equivalent (MME) dose from 30 minutes through 336 hours (Day 15)
Measured: From 30 minutes through 336 hours (Day 15)
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Active Comparator
Numeric Rating Scale at Rest (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).
Measured: From 30 minutes through 336 hours (Day 15)
Difference in NRS-A Pain Intensity Scores During the Timed Up and Go (TUG) Test at Day 15 Compared to Placebo
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).
Measured: Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start3 Feb 2025
- Primary completion3 Oct 2025
- Study completion3 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Total Knee Arthroplasty (Postoperative Pain)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allay Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Hewitt, MD, Study director, Allay Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799845
- Sponsor's protocol ID
- ATX-101-TKA-004
- Acronym
- SPARK2
- Status last verified
- Oct 2026
- First submitted
- 24 Jan 2025
- Last updated
- 19 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2B, Randomized, Double Blind, Placebo and Active Comparator Controlled, Multicenter, Safety, and Efficacy Trial of ATX101 in Adults Undergoing Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT06799845
- Acronym / sponsor ID
- SPARK2 / ATX-101-TKA-004
- Keywords
- postoperative pain, post-surgical pain total knee arthroplasty, bupivacaine, bupivacaine implant, total knee replacement, ATX101, TKA, post-operative pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- Allay Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Feb 2025 (actual)
- Primary completion
- 3 Oct 2025 (actual)
- Study completion
- 3 Oct 2025 (actual)
- First posted
- 29 Jan 2025 (actual)
- Results
- Posted 19 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ATX101 | Experimental | Drug: ATX101 |
| saline placebo | Placebo comparator | Drug: saline placebo |
| bupivacaine hydrochloride | Active comparator | Drug: bupivacaine hydrochloride |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATX101ATX101 bupivacaine implants, total of 1,500 mg into the surgical site | Drug | ATX101 |
| bupivacaine hydrochloridebupivacaine hydrochloride 0.25% without epinephrine/adrenaline, total 125 mg in 50 mL via local periarticular infiltration | Drug | bupivacaine hydrochloride |
| saline placebonormal saline (0.9%) sodium chloride, total volume of up to 17 mL via local periarticular infiltration | Drug | saline placebo |
Primary outcome
Area Under the Curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain Intensity From 30 Minutes Through 168 Hours (Day 8) Compared to Placebo
Time frame: from 30 minutes through 168 hours (Day 8)
Numeric Rating Scale at Rest (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).
5 secondary outcomes
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
Time frame: From 30 minutes through 336 hours (Day 15)
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 504 Hours (Day 22) Compared to Placebo
Time frame: From 30 minutes through 504 hours (Day 22)
Total Post-surgical Consumption of Opioid Medications From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
Time frame: From 30 minutes through 336 hours (Day 15)
AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Active Comparator
Time frame: From 30 minutes through 336 hours (Day 15)
Difference in NRS-A Pain Intensity Scores During the Timed Up and Go (TUG) Test at Day 15 Compared to Placebo
Time frame: Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Enrolling by invitation
Early Outcome of Simultaneous Bilateral Total Knee Replacement With and Without Tourniquet
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Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Hewitt, MD study director
Allay Therapeutics, Inc.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATX101 and bupivacaine hydrochloride in people with Total Knee Arthroplasty (Postoperative Pain), run by Allay Therapeutics, Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain Intensity From 30 Minutes Through 168 Hours (Day 8) Compared to Placebo (time frame: from 30 minutes through 168 hours (Day 8)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.