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First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants

Phase 1
Completed
Conditions
Asthma
Interventions
Registration Number
NCT05366764
Lead Sponsor
Sanofi
Brief Summary

This is a 3-part, parallel group treatment, Phase 1, randomized, double-blind, placebo-controlled study to assess the safety, tolerability and pharmacokinetics after sequential single and multiple ascending doses of SAR443765 in healthy adult participants, and after a single dose of SAR443765 in participants with mild-to-moderate asthma.

Detailed Description

The anticipated study duration per participant is up to 14 weeks

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
Inclusion Criteria
  • Diagnosis of asthma for at least 12 months and confirmed at screening based on the Global Initiative for Asthma (GINA) 2020 Guidelines
  • Controlled asthma defined as no more than 1 canister of rescue inhaler per month over the last 3 months prior to baseline
  • Elevated FeNO level defined as ≥25 ppb
  • Participants, using as-needed SABA, ICS-naïve or with existing stable treatment (at least for 3 months prior to screening) with low to medium daily dose ICS (≤500 mcg of fluticasone propionate or comparable ICS daily dosage) potentially in combination with a LABA and/or LAMA as second controller, and/or with stable daily leukotriene receptor antagonist, leukotriene synthesis inhibitor and/or chromones
  • Prebronchodilator forced expiratory volume in 1 second (FEV1) ≥60% of predicted normal
  • Reversibility of at least 12% and 200 mL in FEV1 or forced vital capacity (FVC) after administration of 4 puffs (400 mcg) of albuterol/salbutamol or levalbuterol/levosalbutamol during screening or documented history of a reversibility test that meets this criteria within 5 years prior to screening or documented positive response to methacholine challenge (a decrease in FEV1 by 20% [PC20] of <8 mg/mL) within 5 years prior to screening visit
  • Body weight between 50.0 and 105.0 kg, inclusive, if male, and between 40.0 and 95.0 kg, inclusive, if female, body mass index between 18.0 and 32.0 kg/m2
  • Male participants are eligible to participate if they use condom during study period
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective
  • A WOCBP must have a negative highly sensitive pregnancy test within 36 hours before the first administration of study intervention
Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

  • Any clinically relevant abnormal findings in medical history, physical examination, vital signs, 12-lead ECG.
  • Chronic lung disease, or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
  • History of life-threatening asthma, asthma exacerbation or use of systemic steroid within 3 months prior to screening visit
  • Worsening of asthma or respiratory infection within the last 6 weeks prior screening visit.
  • Symptomatic postural hypotension,history or presence of drug or alcohol abuse, current smoker or previous smoker with a smoking history >10 pack-years.
  • Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day).

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR443765Salbutamol or levosalbutamolSingle dose administration of SAR443765
PlaceboSalbutamol or levosalbutamolPlacebo to match SAR443765
PlaceboPlaceboPlacebo to match SAR443765
SAR443765SAR443765Single dose administration of SAR443765
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs) /TEAEsFrom baseline up to Day 71

Incidence of adverse events (AEs) and treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures
NameTimeMethod
Change in Nitric Oxide (FeNO) levelDay 1 and Day 29

Change from Baseline in FeNO level at Day 29

Pharmacokinetic (PK) assessment: AUClastFrom baseline up to Day 71

Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast

Presence of Anti-SAR443765 antibodies (ADA)From baseline up to Day 71

Number of participant with SAR443765 antibodies

Total (free + bound) serum target concentrations of IL-13From baseline up to Day 71

Change from baseline in total serum target concentrations of IL-13

Pharmacokinetic (PK) assessment: CmaxFrom baseline up to Day 71

Observed maximum plasma concentration

Pharmacokinetic (PK) assessment: AUCFrom baseline up to Day 71

Area under the serum concentration versus time curve extrapolated to infinity

Total (free + bound) serum target concentrations of TSLPFrom baseline up to Day 71

Change from baseline in total serum target concentrations of TSLP

Trial Locations

Locations (2)

Investigational Site Number : 2760001

🇩🇪

Berlin, Germany

Investigational Site Number : 8260001

🇬🇧

Belfast, United Kingdom

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