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

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 Mastectomy With Immediate Tissue Expander or Implant Placement

This is a multiple center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of brivoligide injection administered intrathecally before surgery in patients with high Pain Catastrophizing Scale (PCS) scores undergoing mastectomy with immediate tissue expander or implant placement.

Study Overview

• Status: Withdrawn
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Brivoligide Injection 660 mg/6 mL; Drug: Placebo 6 mL

Detailed Description

Potential subjects will be prescreened for PCS score; 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).

Subjects will receive study drug just prior to anesthesia induction. Study assessments will be entered by subjects in the electronic diary from Day 1 through Day 21. Follow-up visits will occur on Days 7 and 21 (± 2 days).

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Score of 16 or greater on the PCS scale
• Scheduled to undergo unilateral or bilateral mastectomy with immediate tissue expander or implant placement
• American Society of Anesthesiologists Physical Status Classification System ≤ 3
• Medically stable for this surgery with general anesthesia and intrathecal administration of study drug as determined by the Investigator
• Body mass index of 18-45 kg/m2
• Have a stable medical regimen (for prescribed medications) for ≥ 7 days before randomization
• Able to read and understand study instructions in English or Spanish, and willing and able to comply with all study procedures

Exclusion Criteria:

• Prior breast surgery in the index breast (either breast for bilateral surgery) in the last two years, other than biopsies and small/moderate volume lumpectomies
• Induction chemotherapy or plans for adjunctive chemotherapy or any radiotherapy within 21 days of surgery
• Known spinal deformities or cutaneous infection in the lumbar area that would preclude intrathecal administration of study drug
• Planned use of liposomal formulated or long-acting local anesthetics, extended release opioid formulations (e.g., Oxycontin), long half-life opioids (e.g., methadone), or drugs with potential for adverse cognitive or memory effects (e.g., ketamine, scopolamine, or propranolol) 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
• Unstable mental condition which would prevent the patient from understanding the nature and scope of the study and/or evidence of an uncooperative attitude in the opinion of the Investigator
• Women who are pregnant or nursing
• Participation in a clinical trial with the last dose or intervention within 1 month of randomization, or planned treatment in a clinical trial during this study
• Previous participation in any study involving brivoligide injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brivoligide Injection 660 mg/6 mL; Subjects randomized to the brivoligide treatment group will receive a single 660 mg/6 mL intrathecal administration of brivoligide injection while in the lateral decubitus position at lumbar interspace L3/4 or higher. After injection subjects will be placed supine in a 15-degree head down tilt (Trendelenburg position) for 5 minutes and then returned to supine horizontal for surgery.	Drug: Brivoligide Injection 660 mg/6 mL; Single preoperative intrathecal injection; Other Names: AYX1 Injection 660 mg/6 mL
Placebo Comparator: Placebo 6 mL; Subjects randomized to the placebo group will receive a single 6 mL intrathecal administration of placebo while in the lateral decubitus position at lumbar interspace L3/4 or higher. After injection subjects will be placed supine in a 15-degree head down tilt (Trendelenburg position) for 5 minutes and then returned to supine horizontal for surgery.	Drug: Placebo 6 mL; Single preoperative intrathecal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain with general movement involving the chest and upper body	Least Squares (LS) Mean pain rating with general movement involving the chest and upper body on the 0 - 10 Numerical Rating Scale (0 = No Pain; 10 = Worst Pain)	Day 3 to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at rest	Least Squares (LS) Mean pain rating at rest on the 0 - 10 Numerical Rating Scale (0 = No Pain; 10 = Worst Pain)	Day 3 to Day 14
Pain with deep full inspiration and forceful effective cough	Least Squares (LS) Mean pain rating with deep full inspiration and forceful effective cough on the 0 - 10 Numerical Rating Scale (0 = No Pain; 10 = Worst Pain)	Day 3 to Day 14
Pain with ipsilateral arm abduction	Least Squares (LS) Mean pain rating with ipsilateral arm abduction on the 0 - 10 Numerical Rating Scale (0 = No Pain; 10 = Worst Pain)	Day 14 to Day 21
Total use of postoperative opioid medications	Total use (median) of postoperative opioid medications (morphine equivalents)	Day 3 to Day 14
Total use of postoperative opioid medications	Total use (median) of postoperative opioid medications (morphine equivalents)	Day 1 through Day 21
Change from baseline for the BREAST-Q	Change from baseline to Day 21 for the BREAST-Q	Screening to Day 21

Collaborators and Investigators

• Sponsor: Adynxx, Inc.
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Mastectomy
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: ADYX-006; 1UG3DA048375-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No