Primary objective- To assess the tolerability and safety of SAR444336 after single and repeated ascending subcutaneous doses Secondary objectives- To assess the PK parameters of SAR444336 after single ascending subcutaneous doses (Part 1)- To assess…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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)
Secondary outcome
Plasma PK parameters: Cmax, tmax, AUClast, AUC, t1/2z, CL/F
Anti-SAR444336 antibodies
Background 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.
Study objective
Primary objective
- To assess the tolerability and safety of SAR444336 after single and repeated
ascending subcutaneous doses
Secondary objectives
- To assess the PK parameters of SAR444336 after single ascending subcutaneous
doses (Part 1)
- To assess the PK parameters of SAR444336 after repeated ascending
subcutaneous doses (Part 2)
- To assess anti-drug antibody (ADA) incidence after single and multiple dosing
Exploratory objectives
- To assess the immunophenotyping PD parameters in peripheral blood after
single and repeated ascending subcutaneous doses of SAR444336
- To obtain PD parameters after KLH challenge and repeat doses of SAR444336
(Part 2 only)
- To assess the epigenetics of Tregs
- To assess cytokines secretion in plasma
- To collect DNA samples
- To explore the functionality of Treg cells in vitro
Study design
Phase 1, multiple-center, first-in-human (FIH) study in 2 parts combined under
one study protocol:
• Part 1, SAD; double-blind (sponsor-unblinded), randomized,
placebo-controlled, sequential ascending single doses.
• Part 2, MAD; double-blind (sponsor-unblinded), randomized,
placebo-controlled, sequential ascending repeated doses
Intervention
Subcutaneous injections of SAR444336 or placebo (Part 1 single dose, part 2,
multiple dose for up to 28 days)
Subjects of part B will receive KLH as challenge drug
Study burden and risks
No benefit is expected for healthy volunteers participating in this study.
Considering the measures taken to minimize risk to participants enrolled in
this study, there is no unreasonable and significant risk of illness or injury
for the participants. In this FIH study, healthy participants between 18 and 55
years of age will be included (both men and women in Part 1, men only in Part
2). Specific criteria for inclusion of study participants considering the
mechanism of action of SAR444336 and potential risk associated with treatment,
but also study-specific procedures, will be applied.
Avenue Pierre Brossolette 1
Chilly-mazarin 91380
FR
Avenue Pierre Brossolette 1
Chilly-mazarin 91380
FR
Listed location countries
Age
Inclusion criteria
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
Exclusion criteria
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 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.
- 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 or urine test
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003021-30-NL |
| ClinicalTrials.gov | NCT05876767 |
| CCMO | NL78466.056.21 |