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
- Conditions
- autoimmune disorders10003816inflammatory disorders
- Registration Number
- NL-OMON54131
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 104
Part 1
- 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.
- 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.
Part 2
- Male 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.
- 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.
- Fitzpatrick skin type I - III
Part 1
- Any disease associated with immune system dysfunction.
- Known polyethylene glycol 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.
- Non-live vaccines including: last administration of a vaccine within 4 weeks
before randomization; non-live COVID-19 (booster) vaccination within 14 days
before randomization. First (and second, if applicable) COVID-19 vaccinations
are not allowed within 4 weeks before randomization.
- Live vaccines: Last administration of a vaccine within 3 months before
randomization.
- Immunomodulatory medication within 60 days before screening.
- 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 or urine test.
Part 2
- Participants are excluded from the study if any of the following criteria
apply:
- Any disease associated with immune system dysfunction.
- Known seafood allergy
- Known polyethylene glycol 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 w
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Number of subjects with treatment-emergent adverse events (TEAEs)<br /><br>Clinical laboratory evaluations including eosinophils, procalcitonin, and<br /><br>c-reactive protein (CRP)<br /><br>Vital signs<br /><br>12-lead electrocardiogram (ECG)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Plasma PK parameters: Cmax, tmax, AUClast, AUC, t1/2z, CL/F<br /><br>Anti-SAR444336 antibodies</p><br>