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

Last updated: April 24, 2025
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Overall Status: Active - Recruiting

Phase

1

Condition

Pneumonia

Treatment

FLAMOD

Placebo

Clinical Study ID

NCT06681402
C20-48
2024-515933-14-00
  • Ages 18-65
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • 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 effectivecontraception, males willing to practice contraception or having a partner usingcontraception (if having heterosexual intercourse)

  • non-smoker subject (included e-cigarette smoking) since at least 3 months and ableto not smoke during the whole trial

  • maximum alcohol consumption defined as: i. no more than ten standard glasses perweek; ii. no more than two standard glasses per day; iii. having alcohol-free dayduring the week

  • volunteer should be healthy after a clinical examination

  • affiliation with a social security scheme or beneficiary of such a scheme

Exclusion

Exclusion Criteria:

  • 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., thosewith asplenism, acquired immune deficiency syndrome, or immunoglobulindeficiencies), patients with haematological diseases or solid cancers, solid organor stem-cell transplant recipients, as well as patients with other conditionsrequiring immunosuppression (e.g., rheumatic and autoimmune diseases, inflammatorybowel disease, or multiple sclerosis)

  • administration, less than 5 x t1/2 before FLAMOD's administration, of any medicationor treatment that may alter the FLAMOD immune responses, such as but not limited to:

  • systemic corticosteroids exceeding 10 mg/day of prednisone equivalent for morethan 7 consecutive days or for 10 or more days in total, within 1 month priorto the visit 1. Inhaled and intranasal steroid preparations whatever the dosewithin 1 month prior to the visit 1.

  • cytotoxic, antineoplastic, immunosuppressant drugs including: calcineurininhibitors immunoglobulin, mTOR inhibitors, JAK inhibitors, unspecificimmunosuppressors, TNF-alpha inhibitors, immunosuppressive monoclonalantibodies [e.g., rituximab or infliximab], any anti-cytokine biologicaltreatment (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, orheart rate less than 50 or over 100 bpm)

  • abnormal ECG that is, in the investigator's opinion, clinically significantincluding: heart rate <50 BPM, PR interval > 220 ms, QRS interval ≥ 120 ms, QTcinterval > 450 ms (QT corrected using Bazett's method), second or third-degreeatrioventricular block, any rhythm, other than sinus rhythm, that is interpreted bythe investigator to be clinically significant

  • subjects whose baseline laboratory values are outside of the normal range, as shownin Appendix 3 - Normal laboratory values unless the abnormality is considered not tobe of clinical relevance by the investigator

  • positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody,or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests

  • positive urine nicotine test

  • positive urine multi-drug test

  • abnormal chest x-ray

  • clinically significant abnormality of baseline spirometry tests: forced vitalcapacity (FVC) <90% predicted; forced expiratory volume in one second (FEV1) <80%predicted; FEV1/FVC ratio <80% or diffusion capacity of the lung for carbon monoxide (DLCO) <70% predicted

  • history or presence of drug or chronic alcohol abuse

  • history of severe psychiatric disorders that may affect participation in the trial

  • significant concurrent illness and any other condition that, in the opinion of theinvestigator, would compromise the safety or rights of a volunteer participating inthe trial or render the subject unable to comply with the protocol

  • person subject to a legal protection measure

  • subject in the exclusion period of a previous study

  • known allergy or intolerance to study drug (including any of its constituents, e.g.FLAMOD and polysorbate 80)

Study Design

Total Participants: 60
Treatment Group(s): 2
Primary Treatment: FLAMOD
Phase: 1
Study Start date:
April 14, 2025
Estimated Completion Date:
April 30, 2026

Connect with a study center

  • Centre hospitalier régional universitaire de de Tours

    Tours, 37044
    France

    Active - Recruiting

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