Clinical trial NCT05366764: First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-05-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs) /TEAEs
timeFrame: From baseline up to Day 71
Secondary outcomes:
measure: Pharmacokinetic (PK) assessment: Cmax
timeFrame: From baseline up to Day 71
measure: Pharmacokinetic (PK) assessment: AUClast
timeFrame: From baseline up to Day 71
measure: Pharmacokinetic (PK) assessment: AUC
timeFrame: From baseline up to Day 71
measure: Change in Nitric Oxide (FeNO) level
timeFrame: Day 1 and Day 29
measure: Presence of Anti-SAR443765 antibodies (ADA)
timeFrame: From baseline up to Day 71
measure: Total (free + bound) serum target concentrations of TSLP
timeFrame: From baseline up to Day 71
measure: Total (free + bound) serum target concentrations of IL-13
timeFrame: From baseline up to Day 71
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Belfast
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Deiteren A, Krupka E, Bontinck L, Imberdis K, Conickx G, Bas S, Patel N, Staudinger HW, Suratt BT. A proof-of-mechanism trial in asthma with lunsekimig, a bispecific NANOBODY molecule. Eur Respir J. 2025 Apr 24;65(4):2401461. doi: 10.1183/13993003.01461-2024. Print 2025 Apr.