Study to Evaluate a Preop Dose of Brivoligide Injection for Pain After Knee Replacement in Patients With High PCS Scores

NCT03797612 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ADYX-005
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of brivoligide injection administered intrathecally before surgery in patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing primary unilateral total knee arthroplasty.

Conditions

Pain, Postoperative

Keywords

Knee replacement; TKA; Total Knee Arthroplasty

Outcome Measures

Primary Outcomes (1)

• Numerical Rating Scale (NRS) Pain with Walking 15 Meters

  Least squares mean pain rating (NRS) with walking during the 15-meter walk Day 7 to Day 28

  Day 7 to Day 28

Secondary Outcomes (4)

• Numerical Rating Scale (NRS) Pain at Rest

  Day 7 to Day 28

• Numerical Rating Scale (NRS) Pain with 90 Degrees Passive Knee Flexion

  Day 7 to Day 28

• Total Postoperative Opioid Use

  Postoperative through Day 42

• Time to Numerical Rating Scale (NRS) Pain ≤ 3 for Worst Pain

  Postoperative through Day 42

Study Arms (2)

Brivoligide Injection 660 mg/6 mL

EXPERIMENTAL

Subjects randomized to the active treatment group will receive a single 660 mg/6 mL intrathecal administration of brivoligide injection as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.

Drug: Brivoligide Injection 660 mg/6 mL

Placebo 6 mL

PLACEBO COMPARATOR

Subjects randomized to the placebo group will receive a single 6 mL intrathecal injection of placebo as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.

Drug: Placebo 6 mL

Interventions

Brivoligide Injection 660 mg/6 mL DRUG

Single preoperative intrathecal injection

Also known as: AYX1 Injection 660 mg/6 mL

Brivoligide Injection 660 mg/6 mL

Placebo 6 mL DRUG

Single preoperative intrathecal injection

Placebo 6 mL

Eligibility Criteria

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

You may qualify if:

• Score of 16 or greater on the PCS scale
• Scheduled for primary unilateral TKA with spinal anesthesia as the primary anesthetic for painful osteoarthritis without congenital knee pathology
• American Society of Anesthesiologists Physical Status Classification System ≤ 3
• Medically stable for elective surgery with spinal anesthetic as determined by the Investigator
• Body mass index of 18-45 kg/m2
• Stable medical regimen at least 1 week before randomization
• Able to read and understand study instructions in English or Spanish, and willing to comply with all study procedures

You may not qualify if:

• Target knee \> 20 degrees valgus or varus deformity, evidence of significant bone loss or ligamentous laxity, or existing major hardware that requires removal during TKA
• Inflammatory arthridities (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis), with the exception of clinically stable/non-active gout
• Undergoing concomitant surgical procedures or non-elective TKA, or contralateral knee is likely to require TKA within 6 weeks (or would interfere with study assessments)
• Use of cryoneurolysis (including Iovera) on the current operative knee region within 6 months prior to randomization and/or at any time through the duration of the study
• Planned use of general anesthesia as the primary anesthetic; planned use of neuroaxial (intrathecal or epidural) opioids, or any use of extended release/long acting opioids or 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
• Current neurologic disorder, which could confound the assessment of pain (e.g., Parkinson's, Multiple Sclerosis)
• Unstable mental condition and/or evidence of an uncooperative attitude in the opinion of the Investigator; subjects diagnosed with schizophrenia, prescribed antipsychotic medications or MAOIs
• Women who are pregnant or nursing
• Subjects engaged in pending or active litigation, or seeking disability compensation; subjects whose cases have been settled or finally decided are not excluded
• Participation in a clinical trial with the last dose or intervention within 1 month of randomization, or planned participation in a clinical trial during this study
• Previous participation in any study involving brivoligide injection

Sponsors & Collaborators

• Adynxx, Inc.: lead

Study Sites (2)

Research Site

Sheffield, Alabama, 35660, United States

Location

Research Site

Phoenix, Arizona, 85023, 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 Design

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

Study Record Dates

• First Submitted: January 6, 2019
• First Posted: January 9, 2019
• Study Start: January 1, 2021
• Primary Completion: January 1, 2022
• Study Completion: February 1, 2022
• Last Updated: July 13, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)