Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single and Repeated Doses of SAR444336 in Healthy Adult Participants

Healthy Volunteer Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study of the Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single and Repeated Subcutaneous Doses of SAR444336 in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05876767
• Other study ID #: TDU17072-TDR17161
• Status: Completed
• Phase: Phase 1
• Start date: October 15, 2021
• Est. completion date: December 12, 2023

Study information

• Verified date: July 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase 1 study will assess the safety and tolerability, and characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of SAR444336 in healthy subjects following single- and repeated-dose administrations as a first step in clinical development prior to administering this new investigational medicinal product (IMP) to patients.

Description:

The anticipated study duration per participant is up to 10 weeks in Part 1.

• Screening: 2 to 28 days prior to dosing (Day -28 to Day -2)

• Treatment period: Day -1 to Day 29 post dose including

• Institutionalization: Day -1 until Day 8

• Ambulant period including repeat PK and PD blood sampling and ambulant visits: Day 9 to Day 29

• Follow-up period: Day 30 to Day 43

The anticipated study duration per participant is up to 17 weeks in Part 2.

• Screening: 2 to 28 days prior to dosing (Day -28 to Day -2)

• Treatment period: Day -1 to Day 57 (Q2W/3 doses or Q4W/2 doses) or Day -1 to Day 85 (Q4W/3 doses), or Day -1 to Day 50 (Q3W) including

• Institutionalization: Day -1 until Day 3

• Ambulant period including repeat PK and PD blood sampling, ambulant visits and 24 hours institutionalization after 2nd and/or 3rd dose: Day 4 to Day 57 (Q2W/3 doses, Q4W/2 doses), Day 4 to Day 85 (Q4W/3 doses) or Day 50 (Q3W)

• Follow-up period: Day 58 to Day 71 (Q2W/3 doses or Q4W/2 doses), Day 71 to Day 85 (Q4W/3 doses) or Day 51 to Day 64 (Q3W)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 12, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male and female participants between 18 and 55 years of age inclusive.

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.

• Laboratory values within normal range unless the abnormality is considered not clinical relevant by the investigator. The following parameters, however, must be within normal range: platelet count, and CRP. ALT, AST, total bilirubin (unless the participant has documented or suspected Gilbert syndrome) should be <1.25 ULN and serum creatinine should be < ULN.

• Eosinophils <500 cells/µL

• Normal vital signs after 10 minutes resting in supine position

• Standard 12-lead ECG parameters after 10 minutes resting in supine position in the normal ranges and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant.

• Body weight between 50 - 110 kg (inclusive) and body mass index (BMI) between 18 - 30 kg/m2 (inclusive) at screening.

• Only for part 2: Fitzpatrick skin type I - III

Exclusion Criteria:

• Any disease associated with immune system dysfunction.

• Known polyethylene glycol allergy

• Only for Part 2: Known seafood allergy

• Any current active viral, bacterial or fungal infection or any medically relevant infection having occurred within 3 weeks before inclusion.

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, autoimmune, systemic, ocular, or infectious disease, or signs of acute illness that would pose an unacceptable risk to the subject in the opinion of the investigator.

• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only, more than twice a month).

• Blood donation >500 mL within 2 months before inclusion.

• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure =30 mmHg within 3 minutes when changing from supine to standing position.

• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician, except for history of mild allergic diseases which are not active at the time of inclusion and considered not clinically relevant in the opinion of the investigator.

• History or presence of drug or alcohol abuse.

• Smoking regularly more than 10 cigarettes or equivalent per week, unable to stop smoking during the study (occasional smoker can be enrolled).

• Excessive consumption of beverages containing xanthine bases.

• Presence or history of any atopic disease.

• for Part 1: Non-live booster COVID-19 vaccination within 14 days before randomization. First (and second, if applicable) COVID-19 vaccinations are not allowed within 4 weeks before randomization.

• for Part 2: Non-live vaccines including Covid-19: last administration of a vaccine within 4 weeks before randomization.

• Live vaccines: Last administration of a vaccine within 3 months before randomization; Immunomodulatory medication within 60 days before screening.

• Only for Part 2: Participants with known previous exposure to KLH.

• Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication; any vaccination within the last 28 days (except COVID-19 booster vaccination) and any biologics (antibody or its derivatives) given within 4 months before inclusion.

• Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-HIV1 and anti HIV2 Ab.

• Positive result on urine drug screen.

• Positive alcohol breath test.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• SAR444336
Single or repeated dose subcutaneous injection
• Placebo
Single or repeated dose subcutaneous injection

Locations

Country	Name	City	State
Netherlands	Investigational Site Number :5280002	Groningen
Netherlands	Investigational Site Number :5280001	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of subjects with treatment-emergent adverse events (TEAEs)	Clinical laboratory evaluations including eosinophils, procalcitonin, and c-reactive protein (CRP), Vital signs, 12-lead electrocardiogram (ECG)	Until Day 43
Primary	Part 2: Number of subjects with treatment-emergent adverse events (TEAEs)	Clinical laboratory evaluations including eosinophils, procalcitonin, and c-reactive protein (CRP), Vital signs, 12-lead electrocardiogram (ECG)	Until Day 85
Secondary	Plasma PK parameters: Cmax	Maximum plasma concentration observed	Until Day 29 and Day 85
Secondary	Plasma PK parameters: tmax	Time to reach Cmax	Until Day 29 and Day 85
Secondary	Plasma PK parameters: AUClast	Area under the plasma concentration versus time curve over the dosing interval from time 0 until the last concentration above the limit of quantification	Until Day 29 and Day 85
Secondary	Plasma PK parameters: AUC	Area under the plasma concentration versus time curve extrapolated to infinity	Until Day 29 and Day 85
Secondary	Plasma PK parameters: t1/2z	Terminal half-life	Until Day 29 and Day 85
Secondary	Plasma PK parameters: CL/F	Apparent total body clearance after a single extravascular dose	Until Day 29 and Day 85
Secondary	Anti-SAR444336 antibodies		Until Day 29 and Day 85