A randomized, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending single and multiple doses of SAR446422 in healthy, adult participants
A randomized, placebo-controlled, sequential, participant- and Investigator-masked Phase 1 study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics ( PD) of ascending single and multiple doses of SAR446422 in female and male healthy participants 18 to 55 years of age
Sanofi-Aventis Australia Pty Ltd
120 participants
Dec 5, 2023
Interventional
Conditions
Summary
This is a randomized, placebo-controlled, sequential, participant- and Investigator-masked Phase 1 study to assess the safety, tolerability, PK, and PD of ascending single and multiple doses of SAR446422 in female and male healthy participants 18 to 55 years of age. Number of participants: Up to 120 participants will be randomized to study intervention at a single study site. Part1-SAD17875: approximately 9 dose level cohorts with 8 participants per cohort (6 active and 2 placebo). The last cohort will be optional. Part2-MAD17876: approximately 4 dose level cohorts with 12 participants per cohort (9 active and 3 placebo). The last cohort will be optional.
Eligibility
Inclusion Criteria10
- Participants who are overtly healthy as determined by medical evaluation including medical/surgical history, physical examination, laboratory tests, and cardiac monitoring. Body weight between 50.0 and 110.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, BMI between 18.0 and 32.0 kg/m2, inclusive.
- A female participant not pregnant or breastfeeding, and one of the following conditions applies:
- Is a woman of non-child-bearing potential (WONCBP) or
- Is a woman of child-bearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective
- A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulation) within 36 hours before the first administration of study intervention.
- Male participants who agree to:
- refrain from donating sperm;
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent;
- OR
- Must agree to use contraception/barrier.
Exclusion Criteria9
- Participants are excluded from the study if any of the following criteria apply:
- Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), immunological or infectious disease, or signs of acute illness.
- Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Anaphylaxis from any cause. Known hypersensitivity to any component of the IMP formulation. Previous exposure to KLH or hypersensitivity to shellfish. History of mild, controlled allergy may be included at Investigator’s discretion.
- Any immunization with a non-live vaccine, including against COVID-19, within 4 weeks of enrollment (SAD study Cohort 1 and 2, MAD study) or within 2 weeks of enrollment (SAD study Cohort 3 and higher).
- Any immunization with a live vaccine within 3 months of enrollment.
- Symptomatic herpes zoster within 3 months prior to Screening.
- History of recurrent oral or genital herpes.
- Evidence of active or latent TB as documented by medical history and examination, chest X-rays or a positive QuantiFERON-TB Gold Plus test.
- History of invasive opportunistic infections such as histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, aspergillosis, irrespective of resolution.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
SAR446422 • Formulation: Powder for solution for injection and infusion supplied in a single-use glass vial. Each vial contains 100 mg SAR446422. A precoating solution supplied with SAR446422 is used to coat infusion bags in order to prevent adsorption of SAR446422 to the bag. • Routes of administration: Intravenous (IV) infusion or Subcutaneous ( SC) injection. • Dose regimen: Part 1: - The single ascending dose (SAD) study will include up to 9 cohorts treated with ascending doses, each cohort with single dose, including 5 cohorts of IV infusion with an expected dose range of 0.3 to 30 mg IV infusion followed by up to 4 cohorts with an expected dose range of 75 to 500 mg or less SC injection. Part 2: - The multiple ascending dose (MAD) study will include up to 4 cohorts treated with ascending SC doses with expected doses of up to 30, 60, or 120 mg. Dosing will be SC injection Q2W(Every 2 Weeks) with a total of 3 doses. In the optional MAD cohort (MAD4), any dose lower or higher than in MAD1 through MAD3 may be selected as long as the resulting predicted exposure is lower than the highest exposure in SAD study. - SC administration for cohort 6 and higher in part1, and part2, since it will be mode of administration in later clinical development, For the safety feature, Cohort1-5 in part1 is planned to be administrated by IV infusion. The infusion duration is planned approx. 60mins, there will be an opportunity to stop infusion if acute AEs are observed. - The doses in SAD study and MAD study may be changed based on emerging safety data and PK(Pharmacokinetics), PD(Pharmacodynamics) and ADA (Anti-Drug Antibodies) results . the same group of participants will undertake only one part A nurse will administer the dosage. KLH (keyhole limpet hemocyanin) KLH (Immucothel (Biosyn Corporation) will be used for immunization and DTH challenge in SAD17875 and MAD17876. • Formulation: 54.63 mg powder containing 1 mg KLH and one ampoule with 1 mL solvent, for injection after reconstitution • Routes of administration: IM (intramuscular injection) for immunization and ID (intradermal) for the DTH (delayed-type hypersensitivity) challenge. • Dose regimen: - for immunization, 100 µg of subunit KLH adsorbed to 900 µg aluminum hydroxide (acting as adjuvant for KLH immunization) will be injected IM on Days -12 and 3 (SAD17875 Cohort 3 and higher) and Days 8 and 22 (MAD17876) in the left deltoid muscle. While the planned interval between the first KLH/aluminum IM injection and IMP administration is 12 days, this interval can be as short as 10 days and as long as 14 days. - for the DTH challenge in SAD17875 (Cohort 3 and higher), on Day 17, 1 µg KLH (no adjuvant) will be injected ID in the left forearm (for imaging) and another 1 µg KLH (no adjuvant) will be injected ID at 1 site on the back (between the shoulder blades) (for biopsy 48 hours post injection on Day 19). For the DTH challenge in MAD17876, on Day 36, 1 µg KLH (no adjuvant) will be injected ID in the left forearm (for imaging) and another 1 µg KLH (no adjuvant) will be injected ID at 1 site on the back (between the shoulder blades) (for biopsy 48 hours post injection on Day 38). The ID injection can be administered in a sitting, semi-supine or supine position KLH control • Formulation: 0.9% NaCl solution. • Route of administration: ID. • Dose regimen: there will be no control or placebo for the immunization with KLH/aluminum hydroxide, all participants in Cohort 3 and higher will receive the active immunization. KLH control will be injected on D17 in part 1 and D36 in part 2. As control for the DTH challenge, the same volume as the ID KLH dose described above, injected on Day 17 (SAD17875 Cohort 3 and higher) and Day 36 (MAD17876) in the right forearm and at a site on the back approximately 10 cm from the site of KLH injection (for biopsy 48 hours post injection on Day 38). Precoating solution • Formulation: Coating solution for infusion supplied in a single-use glass vial. Each vial contains 16 mL precoating solution (48 mg polysorbate 80). • Routes of administration: IV infusion. • Dose regimen: IV dosages for which the infusion bag is required. Aluminum hydroxide Aluminum hydroxide (Alhydrogel, Croda International) will be used as adjuvant for KLH immunization in SAD17875 and MAD17876. • Formulation: 900 µg aluminum hydroxide adsorbed to KLH. • Route of administration: IM. • Dose regimen: as described above for KLH adsorbed to aluminum hydroxide.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12623001176651