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

Primary Purpose

Pain, Postoperative

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Brivoligide Injection 660 mg/6 mL

Placebo 6 mL

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring Knee replacement, TKA, Total Knee Arthroplasty

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Brivoligide Injection 660 mg/6 mL

Placebo 6 mL

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Numerical Rating Scale (NRS) Pain at Rest

Least squares mean pain rating (NRS) at rest Day 7 to Day 28

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

Least squares mean pain rating (NRS) with passive knee flexion to 90 degrees from Day 7 to Day 28

Total Postoperative Opioid Use

Total use of postoperative opioid medications (morphine equivalents) to Day 42

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

Time to achieve NRS pain score ≤ 3 for worst pain

Full Information

NCT ID

NCT03797612

First Posted

January 6, 2019

Last Updated

July 9, 2020

Sponsor

Adynxx, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03797612

Brief Title

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

Official Title

A Phase 2 Randomized Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Single Intrathecal Preoperative Administration of Brivoligide Injection in Patients With a Pain Catastrophizing Scale Score ≥16 Undergoing Unilateral Total Knee Arthroplasty

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Study initiation delayed due to COVID 19

Study Start Date

January 2021 (Anticipated)

Primary Completion Date

January 2022 (Anticipated)

Study Completion Date

February 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Adynxx, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

The objective of this study is to evaluate the safety and postoperative pain reducing efficacy of a single preoperative intrathecal administration of brivoligide injection in patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing unilateral total knee arthroplasty. Potential subjects will be prescreened for PCS scores of 16 or greater in advance; pre-qualified patients will be invited to the investigative site for informed consent and full screening within 30 days of randomization. Patients providing informed consent and meeting all study eligibility criteria will be enrolled in the study on the day of surgery (Day 1). Safety assessments will be performed through Day 28; efficacy assessments will be conducted at the follow-up visits and daily via electronic diary by subjects through Day 42. Follow up visits will occur on Days 7, 14, 21, 28, and 42.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pain, Postoperative

Keywords

Knee replacement, TKA, Total Knee Arthroplasty

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Brivoligide Injection 660 mg/6 mL

Arm Type

Experimental

Arm Description

Arm Title

Placebo 6 mL

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Brivoligide Injection 660 mg/6 mL

Other Intervention Name(s)

AYX1 Injection 660 mg/6 mL

Intervention Description

Single preoperative intrathecal injection

Intervention Type

Drug

Intervention Name(s)

Placebo 6 mL

Intervention Description

Single preoperative intrathecal injection

Primary Outcome Measure Information:

Title

Numerical Rating Scale (NRS) Pain with Walking 15 Meters

Description

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

Time Frame

Day 7 to Day 28

Secondary Outcome Measure Information:

Title

Numerical Rating Scale (NRS) Pain at Rest

Description

Least squares mean pain rating (NRS) at rest Day 7 to Day 28

Time Frame

Day 7 to Day 28

Title

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

Description

Least squares mean pain rating (NRS) with passive knee flexion to 90 degrees from Day 7 to Day 28

Time Frame

Day 7 to Day 28

Title

Total Postoperative Opioid Use

Description

Total use of postoperative opioid medications (morphine equivalents) to Day 42

Time Frame

Postoperative through Day 42

Title

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

Description

Time to achieve NRS pain score ≤ 3 for worst pain

Time Frame

Postoperative through Day 42

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Facility Information:

Facility Name

Research Site

City

Sheffield

State/Province

Alabama

ZIP/Postal Code

35660

Country

United States

Facility Name

Research Site

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85023

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data will not be made available to other researchers.

Learn more about this trial

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

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