Phase I Single-blind Clinical Trial to Evaluate the Safety and Local Immune Activation of a Toll-like Receptor 5 Agonist (FLAMOD) Administered by Aerosol

NCT06681402 | Completed Phase 1 DMC

• 2 other identifiers: C20-482024-515933-14-00
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-blind, randomized, placebo-controlled, dose-escalation phase I monocentric trial assessing a single administration of FLAMOD by aerosol in healthy subjects. The recruitment is performed by the Clinical Investigation Center of Tours. This trial is divided in two stages:

• the "start-up phase" consisting of a dose escalation to ensure the safety of FLAMOD while allowing sufficient information on the molecule activity to be accumulated
• the dose-finding phase estimating several dose-activity models and then selecting the one that best fits the data to then propose the dose for the next cohort of participants.

Conditions

Pneumonia

Keywords

Immunotherapy; Inhalation; Antibiotic resistance; Flagellin; Pneumonia

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of a single administration dose of FLAMOD

  The safety of FLAMOD is assessed via the proportion of Serious Adverse Events, critical safety events, serious adverse reactions, and cytokine release syndrome grade 2 and above. The tolerability of FLAMOD is assessed via the proportion of treated participants who experience laboratory abnormalities and/or Adverse Events as defined by Common Terminology Criteria for Adverse Events v5.0.

  From enrollment to the end of follow-up (at 2 weeks +/- 4 days post administration)

Secondary Outcomes (4)

• FLAMOD immune activating dose (IAD)

  From enrollment to visit 2 (24 hours + 3-day window post administration)

• Local immune-enhancing effect of FLAMOD on nasal epithelial lining fluid

  From enrollment to visit 2 (24 hours + 3-day window post administration)

• Local immune-enhancing effect of FLAMOD on nasal epithelial cells

  From enrollment to visit 2 (24 hours + 3-day window post administration)

• Systemic immune-enhancing effect of FLAMOD

  From enrollment to visit 2 (24 hours + 3-day window post administration)

Study Arms (2)

FLAMOD

EXPERIMENTAL

Drug: FLAMOD

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

FLAMOD DRUG

FLAMOD (GMP-grade flagellin) inhalation

FLAMOD

Placebo DRUG

Placebo inhalation

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• provision of signed and dated informed consent form
• stated willingness to comply with all trial procedures, clinic visits, blood draws, and availability for the duration of the trial
• human subjects who are between 18 and 65 years of age
• weight of at least 50 kg and body mass index (BMI) within the range of 18 - 30 kg/m²
• females of non-childbearing potential or of childbearing potential with effective contraception, males willing to practice contraception or having a partner using contraception (if having heterosexual intercourse)
• non-smoker subject (included e-cigarette smoking) since at least 3 months and able to not smoke during the whole trial
• maximum alcohol consumption defined as: i. no more than ten standard glasses per week; ii. no more than two standard glasses per day; iii. having alcohol-free day during the week
• volunteer should be healthy after a clinical examination
• affiliation with a social security scheme or beneficiary of such a scheme

You may not qualify if:

• febrile and/or suspected infection
• history of chronic pulmonary disease
• history of acute pulmonary disease in the past 6 months
• immunocompromised individuals, which includes immunodeficient patients (e.g., those with asplenism, acquired immune deficiency syndrome, or immunoglobulin deficiencies), patients with haematological diseases or solid cancers, solid organ or stem-cell transplant recipients, as well as patients with other conditions requiring immunosuppression (e.g., rheumatic and autoimmune diseases, inflammatory bowel disease, or multiple sclerosis)
• administration, less than 5 x t1/2 before FLAMOD's administration, of any medication or treatment that may alter the FLAMOD immune responses, such as but not limited to:
• systemic corticosteroids exceeding 10 mg/day of prednisone equivalent for more than 7 consecutive days or for 10 or more days in total, within 1 month prior to the visit 1. Inhaled and intranasal steroid preparations whatever the dose within 1 month prior to the visit 1.
• cytotoxic, antineoplastic, immunosuppressant drugs including: calcineurin inhibitors immunoglobulin, mTOR inhibitors, JAK inhibitors, unspecific immunosuppressors, TNF-alpha inhibitors, immunosuppressive monoclonal antibodies \[e.g., rituximab or infliximab\], any anti-cytokine biological treatment (e.g. TNF-alpha inhibitors, anti-IL6 agents, anti-IL1 agents); within 12 months prior to the visit 1.
• concurrent immunostimulant drugs or biologic agents including: growth factors, cytokines, interleukins, interferons; within 12 months prior to the visit 1.
• administration of vaccine within 1 month prior to visit 1.
• administration of anticoagulant treatments: warfarin (coumadin), fondaparinux, heparin (unfractionated Heparin), low molecular weight heparin (enoxaparin, dalteparin), direct oral anticoagulants (rivaroxaban, apixaban, edoxaban, dabigatran); within 1 week prior to the visit 1
• pregnant or lactating woman
• inability to tolerate a nebulization test with saline
• clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 150 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm)
• abnormal ECG that is, in the investigator's opinion, clinically significant including: heart rate \<50 BPM, PR interval \> 220 ms, QRS interval ≥ 120 ms, QTc interval \> 450 ms (QT corrected using Bazett's method), second or third-degree atrioventricular block, any rhythm, other than sinus rhythm, that is interpreted by the investigator to be clinically significant
• subjects whose baseline laboratory values are outside of the normal range, as shown in Appendix 3 - Normal laboratory values unless the abnormality is considered not to be of clinical relevance by the investigator

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• European Union: collaborator

Study Sites (1)

Centre hospitalier régional universitaire de de Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Pneumonia; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antoine Guillon, MD

  Centre Hospitalier Régional Universitaire de Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 8, 2024
• Study Start: April 14, 2025
• Primary Completion: April 17, 2026
• Study Completion: April 17, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)