Study to Evaluate Safety/Efficacy of a Single Preop Dose of AYX1 Injection to Treat Pain After Knee Replacement Surgery

Phase 2

Completed

Conditions: Post-surgical Pain

Interventions: Drug: AYX1 Injection 660 mg/6 mL
Drug: Placebo Injection 6 mL

Registration Number: NCT02807428

Lead Sponsor: Adynxx, Inc.

Brief Summary: The objectives of this study are to evaluate the safety and analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection in patients undergoing unilateral total knee arthroplasty.

Detailed Description: This is a multi-center, Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of AYX1 Injection administered intrathecally before surgery in patients undergoing primary unilateral total knee arthroplasty (TKA). Subjects will be randomized on the day of surgery to receive either intrathecal AYX1 Injection or intrathecal placebo just prior to surgery. Study assessments will be conducted during the inpatient period through 48 hours; follow-up visits will be performed through Study Day 90.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 210

Inclusion Criteria

Scheduled to undergo primary unilateral TKA with spinal anesthesia for painful osteoarthritis without congenital knee pathology
American Society of Anesthesiologists Physical Status Classification System ≤ 3
Medically stable as determined by the Investigator based on pre-study medical history, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
Body Mass Index of 18-45 kg/m2
Stable medical regimen for at least 1 week before randomization
Able to read and understand study instructions in English, and willing and able to comply with all study procedures

Exclusion Criteria

More than 2 other current focal areas of pain, any pain areas greater in intensity than the target knee, or any other active chronic pain conditions that would compromise operative knee pain evaluation
Inflammatory arthridities (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis), with the exception of clinically stable/non-active gout that does not affect the knee and does not interfere with walking
Surgery in either knee within 3 months prior to randomization, or surgery in either knee greater than 3 months prior to randomization with residual symptoms that would interfere with post-TKA study assessments; use of cryoneurolysis (including Iovera) on the current operative knee region within the 6 months prior to randomization and/or at any time through the duration of the study
Planned use of general anesthesia or potent inhalational agents, peripheral nerve block (e.g., femoral nerve block), neuroaxial (intrathecal or epidural) opioids, preoperative extended release/long acting opioids, or any use of ketamine preoperatively and/or at any time through the duration of the study
Use of more than 40 mg per day (on average) of oral morphine or its equivalent within 1 month prior to randomization
Use of gabapentin or pregabalin within 1 week prior to randomization or planned use post-operatively through Day 28
Use of systemic corticosteroids (IV or oral) within 3 months prior to randomization through Day 28; planned use of intra-articular steroid injections in the operative knee from the time of randomization through Day 28
Current neurologic disorder, which could confound the assessment of pain (e.g., Parkinson's, Multiple Sclerosis)
Untreated or inadequately treated (in the opinion of the Investigator) active depression
Mini Mental State Exam score < 24 at screening
History of alcohol-related complications within 1 year of randomization including, but not limited to, alcoholic withdrawal seizures, hallucinations, delirium tremens or detoxification treatment
Known or suspected history of illicit drug use within 1 year before randomization, or current or planned use of marijuana (including medical approved use) within 1 month before randomization and/or through the duration of the study
Any confirmed malignancy within the past year, with the exception of basal cell carcinoma or uncomplicated or stable skin cancers documented to not require further or immediate treatment
Women who are pregnant or nursing
Previous participation in any study involving AYX1 Injection

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AYX1 Injection 660 mg/6 mL	AYX1 Injection 660 mg/6 mL	Single Intrathecal (spinal) administration of AYX1 Injection (660 mg in 6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery.
Placebo Injection 6 mL	Placebo Injection 6 mL	Single Intrathecal (spinal) administration of Placebo Injection (6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Primary Outcome Measures

Name	Time	Method
Mean pain with walking during the 15 meter walk test Day 7 to Day 28	7-28 days post-surgery	Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during the outpatient period from Day 7 to Day 28

Secondary Outcome Measures

Name	Time	Method
Total use of postoperative opioid medications (morphine equivalents) post-discharge to Day 90	post-hospital discharge through 90 days post-surgery	Total use of postoperative opioid medications (morphine equivalents) post-discharge to Day 90
Percentage of subjects with NRS pain score ≥ 4 during the 15 meter walk at Day 90	at 90 days post-surgery	Percentage of subjects with the Numerical Rating Scale (NRS) pain score ≥ 4 during the 15 meter walk at Day 90
Mean pain rating (NRS) at rest Day 7 to Day 28	7-28 days post-surgery	Mean pain rating with the Numerical Rating Scale (NRS) at rest Day 7 to Day 28

Trial Locations

Locations (9): Mississippi Sports Medicine
🇺🇸
Jackson, Mississippi, United States
Arizona Research Center
🇺🇸
Phoenix, Arizona, United States
Alabama Orthopedic Center
🇺🇸
Birmingham, Alabama, United States
Shoals Medical Trials
🇺🇸
Sheffield, Alabama, United States
Pensacola Research Consultants
🇺🇸
Pensacola, Florida, United States
Phoenix Clinical Research
🇺🇸
Tamarac, Florida, United States
Antria, Inc.
🇺🇸
Indiana, Pennsylvania, United States
The Ohio State University Wexner Medical Center
🇺🇸
Columbus, Ohio, United States
CORE Orthopaedic Medical Center
🇺🇸
Encinitas, California, United States