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

NCT02807428 | Completed Phase 2 FDA Drug

• 1 other identifier: ADYX-004
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 9

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.

Conditions

Post-surgical Pain

Keywords

post-surgical pain; total knee arthroplasty; total knee replacement

Outcome Measures

Primary Outcomes (1)

• Mean pain with walking during the 15 meter walk test Day 7 to Day 28

  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

  7-28 days post-surgery

Secondary Outcomes (3)

• Percentage of subjects with NRS pain score ≥ 4 during the 15 meter walk at Day 90

  at 90 days post-surgery

• Mean pain rating (NRS) at rest Day 7 to Day 28

  7-28 days post-surgery

• Total use of postoperative opioid medications (morphine equivalents) post-discharge to Day 90

  post-hospital discharge through 90 days post-surgery

Study Arms (2)

AYX1 Injection 660 mg/6 mL

EXPERIMENTAL

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

Drug: AYX1 Injection 660 mg/6 mL

Placebo Injection 6 mL

PLACEBO COMPARATOR

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

Drug: Placebo Injection 6 mL

Interventions

AYX1 Injection 660 mg/6 mL DRUG

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

Also known as: Brivoligide 660 mg/6 mL

AYX1 Injection 660 mg/6 mL

Placebo Injection 6 mL DRUG

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

Placebo Injection 6 mL

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adynxx, Inc.: lead

Study Sites (9)

Alabama Orthopedic Center

Birmingham, Alabama, 35209, United States

Location

Shoals Medical Trials

Sheffield, Alabama, 35660, United States

Location

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

CORE Orthopaedic Medical Center

Encinitas, California, 92024, United States

Location

Pensacola Research Consultants

Pensacola, Florida, 32503, United States

Location

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

Location

Mississippi Sports Medicine

Jackson, Mississippi, 39202, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Antria, Inc.

Indiana, Pennsylvania, 15701, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

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

Study Officials

• Donald C Manning, MD, PhD

  Adynxx, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: February 20, 2017
• Primary Completion: October 23, 2017
• Study Completion: December 19, 2017
• Last Updated: October 17, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)