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

NCT ID: NCT02807428

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2017-12-19

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.

Conditions

Post-surgical Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

AYX1 Injection 660 mg/6 mL

Intervention Type: DRUG

6 mL solution for intrathecal injection with 660 mg of AYX1 (Brivoligide)

Placebo Injection 6 mL

Single Intrathecal (spinal) administration of Placebo Injection (6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Group Type: PLACEBO_COMPARATOR

Placebo Injection 6 mL

Intervention Type: DRUG

6 mL solution for intrathecal injection; vehicle formulation designed to mimic AYX1 Injection (with no active drug)

Interventions

AYX1 Injection 660 mg/6 mL

6 mL solution for intrathecal injection with 660 mg of AYX1 (Brivoligide)

Intervention Type: DRUG

Placebo Injection 6 mL

6 mL solution for intrathecal injection; vehicle formulation designed to mimic AYX1 Injection (with no active drug)

Intervention Type: DRUG

Other Intervention Names

Brivoligide 660 mg/6 mL

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adynxx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald C Manning, MD, PhD

Role: STUDY_DIRECTOR

Adynxx, Inc.

Locations

Alabama Orthopedic Center

Birmingham, Alabama, United States

Shoals Medical Trials

Sheffield, Alabama, United States

Arizona Research Center

Phoenix, Arizona, United States

CORE Orthopaedic Medical Center

Encinitas, California, United States

Pensacola Research Consultants

Pensacola, Florida, United States

Phoenix Clinical Research

Tamarac, Florida, United States

Mississippi Sports Medicine

Jackson, Mississippi, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Antria, Inc.

Indiana, Pennsylvania, United States

Countries

United States

Other Identifiers

ADYX-004

Identifier Type: -

Identifier Source: org_study_id