A First in Human Study of TT5 in Single and Multiple Ascending Doses in Healthy Volunteers and Surgical Patients (TAFA-FIRST)

A First in Human, Three-part, Double Blind, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study to Investigate Safety and Pharmacokinetics of TT5 in Healthy Participants and Surgical Patients

This study is a First in Human, three-parts, double-blind, randomized, placebo-controlled, single and multiple ascending dose study. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TT5 at different doses in healthy and surgical participants.

Study Overview

• Status: Recruiting
• Conditions: Pain
• Intervention / Treatment: Drug: TT5; Drug: Placebo - TT5 vehicle

Detailed Description

The study will be divided into three parts:

Part A: Single Ascending Dose - healthy participants cohorts with up to 5 dose levels.

Part B: Multiple Ascending Doses - healthy participants cohorts with up to 3 dose levels.

Part C: Surgical patients cohorts with up to 3 dose levels.

The primary Objective is to investigate the safety and tolerability of TT5 in single and multiple ascending intravenous doses in healthy participants and in surgical patients.

The Secondary Objectives are To investigate the pharmacokinetics (PK) of TT5 after single and multiple ascending intravenous doses in healthy participants and after intravenous doses in surgical patients.

• To investigate the acute and chronic psychological subjective response of the healthy participants and surgical patients to TT5
• To assess the pharmacodynamics (PD) of TT5 after intravenous doses in surgical patients. Exploratory Objectives areto explore potential fluid biomarkers for TT5

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Olivier Blin, M.D., PhD; Phone Number: +33781637056; Email: Olivier.blin@tafalgie.fr

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Cmax & PARC
      • Contact: Natasha Payne; Phone Number: +61 8 7088 7900; Email: cmax@cmax.com.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Main inclusion criteria for Parts A and B:

• Non-smoker for the confinement period of the study.
• Medically healthy and without clinically significant abnormalities.
• Negative screen for alcohol and drugs of abuse.
• No history of psychiatric disorders.
• Female participants of non-childbearing potential must be post-menopausal or surgically sterile at least 3 months prior to dosing.
• Sexually active females of childbearing potential and non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
• Able to understand the study procedures and provide signed informed consent to participate in the study in English.

Main exclusion criteria for Parts A and B:

• History of clinically significant asthma, anaphylaxis, major medical, psychiatric illness or surgery.
• Acute or chronic clinically relevant systemic disease or disorder.
• Renal insufficiency
• History of drug or alcohol consumption abuse.
• Drinking excessive amounts of tea, coffee, chocolate and/or beverage containing caffeine.
• Have used any investigational drug or participated in any clinical trial within 4 weeks prior to screening.
• Unable to refrain from strenuous exercise.
• Participant who has received blood or plasma derivatives, who had a surgery or who has given blood within 4 weeks prior to the screening visit or has planned to give blood or sperm within the 90 days following the study.
• Pregnant or lactating female participant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TT5	Drug: TT5; Direct Intravenous administration of TT5 (5 ascending doses in Single Ascending Dose Part and 3 ascending doses administered during 7 days in Multiple Ascending Dose Part in healthy volunteers) Direct Intravenous administration of TT5 in surgical patients (4 doses administered on the same day) in surgical patients
Placebo Comparator: TT5 vehicle	Drug: Placebo - TT5 vehicle; Intravenous administration of vehicule, according to the same drug regimen than TT5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and serious adverse events (SAEs)	Number of AEs and SAEs:To investigate the safety and tolerability of TT5	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
Clinically significant changes in physical examinations	% of participants with clinically significant changes from baseline in physical examinations by measuring general appearance, head, eyes, ears, nose, throat (HEENT), neck (including thyroid and nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, and skin.	SAD cohorts: Baseline through Day 8; MAD cohorts: Baseline through Day 14
Clinically significant changes in vital signs	% of participants with clinically significant change from baseline in vital signs by measuring heart rate, blood pressure, temperature, and respiratory rate	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
Clinically significant changes in laboratory analysis	Mean and SD of clinically significant changes from baseline in laboratory analysis including hematology, coagulation, biochemistry, and urinalysis	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
Bond and Lader Visual Analog Scale (VAS)	VAS item values: To assess vigilance will using a Visual Analogic Scale namely the Bond-Lader VAS of Mood and Alertness	SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma AUC0-t measurement	Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) h*ng/ml	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma AUC0-inf measurement	Area under the concentration-time curve from time zero to infinity (AUC0-inf) h*ng/ml	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma Cmax measurement	Maximum concentration measurement in plasma (ng/ml)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma Tmax measurement	Time to maximum observed concentration in plasma (hours)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma T½ el measurement	Terminal elimination half-life (T½ el) in plasma (hours)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma Kel measurement	Terminal elimination rate constant (Kel) in plasma (fraction/h)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma Cl/F measurement	Apparent clearance (Cl/F) in plasma (mL/min)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Plasma Vz/F measurement	Apparent volume of distribution (Vz/F) in plasma (liters)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Urine CLr measurement	Renal clearance measurement in urine (mL/min)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Urine Aet1-t2 measurement	Amount excreted in urine (Aet1-t2) per interval (mL/min)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Urine Ae0-t measurement	Cumulative urinary excretion from time zero to time t (Ae0-t) ( (mL/min)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Urine Ae%dose measurement	% of drug recovered in urine (Ae%dose)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
ARCI	Total Score and Sub-scores of Addiction Research Center Inventory questionnaire to investigate subjective effects	SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Fluid Biomarkers concentration (pmol/ml)	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8

Collaborators and Investigators

• Sponsor: Tafalgie Therapeutics
• Investigators: Principal Investigator: Guy Ludbrook, MD, University of Adelaide and Royal Adelaide Hospital.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 10, 2026

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 23, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain
• Other Study ID Numbers: P-TT5-PH1-001

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No