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

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of SAR443765 in Healthy Adult Participants and of a Single Dose of SAR443765 in Participants With Mild-to-moderate Asthma

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: SAR443765; Drug: Salbutamol or levosalbutamol; Drug: Placebo

Detailed Description

The anticipated study duration per participant is up to 14 weeks

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number :2760001
• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Investigational Site Number :8260001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR443765; Single dose administration of SAR443765	Drug: SAR443765; solution for injection; Drug: Salbutamol or levosalbutamol; metered dose inhaler
Placebo Comparator: Placebo; Placebo to match SAR443765	Drug: Salbutamol or levosalbutamol; metered dose inhaler; Drug: Placebo; solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) /TEAEs	Incidence of adverse events (AEs) and treatment-emergent adverse events (TEAEs)	From baseline up to Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) assessment: Cmax	Observed maximum plasma concentration	From baseline up to Day 71
Pharmacokinetic (PK) assessment: AUClast	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast	From baseline up to Day 71
Pharmacokinetic (PK) assessment: AUC	Area under the serum concentration versus time curve extrapolated to infinity	From baseline up to Day 71
Change in Nitric Oxide (FeNO) level	Change from Baseline in FeNO level at Day 29	Day 1 and Day 29
Presence of Anti-SAR443765 antibodies (ADA)	Number of participant with SAR443765 antibodies	From baseline up to Day 71
Total (free + bound) serum target concentrations of TSLP	Change from baseline in total serum target concentrations of TSLP	From baseline up to Day 71
Total (free + bound) serum target concentrations of IL-13	Change from baseline in total serum target concentrations of IL-13	From baseline up to Day 71

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 4, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: PDY16622; 2021-000356-19 (EudraCT Number); U1111-1265-6232 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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