Dose Finding Study of STR-324

A Proof of Concept Randomized, Double-blind, Parallel Group, Controlled Dose-finding and Safety Study of STR-324 in Post-operative Pain

This study aims to evaluate the analgesic effect and the safety of 4 doses of STR-324 administered as an infusion, with or without initial bolus, to patients suffering from post-operative pain.

The sensitivity of the pain model used in the trial will be evaluated with a standard group treated with morphine under the usual care conditions.

Study Overview

• Status: Recruiting
• Conditions: Pain, Acute
• Intervention / Treatment: Drug: Morphine; Drug: Morphine HCl; Drug: STR-324

Detailed Description

The first step (single-blind standard group) aims to verify the sensitivity of the study pain model in the proposed surgery to confirm the validity of the surgery according to their pain and enrolment rate. 12 patients are planned to be enrolled.

The second step (dose-finding study) is a randomized, double-blind, parallel groups, controlled clinical trial involving a total of 106 patients divided into two groups in which patients will be randomized between STR-324 and morphine HCl:

• Group 1: Titration initiated with a bolus
• Group 2: Titration without initial bolus.

• Study Type: Interventional
• Enrollment (Anticipated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Annie-Claude Benichou; Phone Number: +33 4 78 42 95 26; Email: clinical@bioalaxia.eu
• Study Contact Backup: Name: Pascale Vermare; Phone Number: +33 4 37 53 26 60; Email: clinical@bioalaxia.eu

Study Locations

• Netherlands
  • Leiden, Netherlands, H05-22
    • Recruiting
    • Leiden University Medical Center
    • Contact: Monique Van Velzen; Phone Number: +31 71 526 2301; Email: M.van_Velzen@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Selection criteria:

1. Patient aged ≥18 to <65 years old, at screening;
2. Having signed an informed consent prior to any study-related procedure;
3. Patients planned to undergo a major laparoscopic abdominal or pelvic surgery;
4. Surgery to be performed without local or regional anaesthesia nor infiltration;
5. Body mass index (BMI) between 18 and 30 kg/m² inclusive at screening, and with a minimum weight of 50 kg;
6. Women of childbearing potential must agree to use at least one effective contraceptive method upon enrolment and for 1 cycle following the last dose of the investigational product.

Inclusion Criteria:

The criteria for definitive enrolment must be checked in the Post-Anaesthesia Care Unit (PACU) at the inclusion visit:

1. NRS-measured pain intensity ranging from 4 to 8 inclusive at baseline PACU measurement;
2. With a sedation score ≤ S1 (awake or intermittently sleepy) at the time of pain assessment.

Exclusion Criteria:

1. Patient contra-indicated for morphine administration;
2. Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, major anxiety, or depression). Subjects who take stable doses (same dose >30 days) of antidepressants and/or anti-anxiety drugs may be included;
3. Women who are pregnant or breastfeeding;
4. History of alcohol, opiate or other drug abuse.
5. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment might interfere with the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator. Minor deviations of values from the normal range may be accepted, if judged by the Investigator to have no clinical relevance;
6. Clinically significant abnormalities, as judged by the investigator, in laboratory test results;
7. Participation in an investigational drug or device study within 1 month prior to dosing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard group; Standard treatment (morphine) administered according to usual practice	Drug: Morphine; Repeated bolus according to pain score
Experimental: Test group: Infusion with bolus; STR-324 or morphine HCl infusion started with a initial bolus	Drug: Morphine HCl; Infusion of morphine HCl solution for intravenous administration; Drug: STR-324; Infusion of solution for intravenous administration
Experimental: Test group: Infusion without bolus; STR-324 or morphine HCl infusion started without a initial bolus	Drug: Morphine HCl; Infusion of morphine HCl solution for intravenous administration; Drug: STR-324; Infusion of solution for intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative Change of Pain Intensity	Pain Intensity will be assessed by a Numerical Rating Scale (NRS) before and during analgesic infusion. Change of Pain Intensity assessed by the Numerical Rating Scale (NRS) after initiation of the post-op analgesia and before switch to standard treatment. The following parameter will be assessed: - Qualitative: a decrease of 2 units minimum from baseline and/or achievement of a pain score ≤ 3 is considered successful, responder=Yes.	On and/or after study drug, with fixed timepoints at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes. If re-titration is required/performed, additional 5-minutes interval timepoints shall be added.
Quantitative Change of Pain Intensity	Pain Intensity will be assessed by a Numerical Rating Scale (NRS) before and during analgesic infusion. Change of Pain Intensity assessed by the Numerical Rating Scale (NRS) after initiation of the post-op analgesia and before switch to standard treatment. The following parameter will be assessed: - Quantitative: maximum value of the pain score difference versus baseline.	On and/or after study drug, with fixed timepoints at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes. If re-titration is required/performed, additional 5-minutes interval timepoints shall be added.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events collection	Any untoward medical occurrence in a patient or a clinical investigation subject, which does not necessarily have a causal relationship with the study treatment.	AEs collected directly after surgery until at least 30 days after the day of surgery.

Collaborators and Investigators

• Sponsor: Alaxia SAS

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 13, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: STR-324-CL-072; 2019-003019-80 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

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