Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1920 in Healthy Participants
- Registration Number
- NCT05751642
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single ascending doses (SADs) of ALXN1920 subcutaneous (SC) and of a single dose of ALXN1920 intravenous (IV) in healthy adult participants.
- Detailed Description
This is a first-in-human study in healthy adult participants.
Eligible participants will be randomly assigned in a 3:1 (ALXN1920:Placebo) ratio in each of the treatment cohorts. The first 2 participants randomized to each cohort will be dosed as a sentinel pair, with 1 participant on active treatment and 1 participant on placebo. At the discretion of the Investigator, up to 3 more participants will be added at least 48 hours after the dosing of the sentinel pair, followed by dosing of the remaining participants in the cohort no earlier than 72 hours after sentinel pair dosing.
The study will comprise:
A Screening Period of up to 28 days; A Dosing Period (single dose through to Follow-up Visit) of approximately 28 days; A Final Follow-up period and end of study Visit is planned on Day 29.
Each participant will be involved in the study for approximately 56 days.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- Healthy participants
- Body mass index within 18.0 to 32.0 kg/m^2 (inclusive), with a minimum body weight of 50.0 kg.
- Female participants of childbearing potential and male participants must follow protocol-specified contraception guidance.
- For Cohort 6, participants of Japanese descent, defined as having both parents and 4 grandparents who are ethnically Japanese.
- Significant history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
- History of significant allergic reaction.
- History of any Neisseria infection
- Active systemic bacterial, viral, or fungal infection.
- Participants who at Day -1 are either testing positive for coronavirus disease 2019 (COVID-19), or have not had at least 4 weeks elapse of recovery time (a negative test), or are experiencing long-term COVID-19-related sequelae.
- Any major surgery within 8 weeks of Screening.
- Known or suspected history of drug or alcohol abuse.
- Current tobacco users or smokers.
- Positive Human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C viral infection.
- Female participant who are pregnant, breastfeeding, or intending to conceive during the course of the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 ALXN1920 Participants will receive a single dose of ALXN1920. Cohort 3 ALXN1920 Participants will receive a single dose of ALXN1920. Cohort 5 ALXN1920 Participants will receive a single dose of ALXN1920. Pooled Placebo Placebo Participants will receive Placebo. Cohort 4 ALXN1920 Participants will receive a single dose of ALXN1920. Cohort 6: Japanese Cohort ALXN1920 Japanese participants will receive a single dose of ALXN1920. Cohort 2 ALXN1920 Participants will receive a single dose of ALXN1920.
- Primary Outcome Measures
Name Time Method Number of participants with Adverse events (AEs) Up to End of study visit (Day 29) To assess the safety and tolerability of single ascending doses of ALXN1920.
- Secondary Outcome Measures
Name Time Method Area under the concentration-time curve from time 0 (dosing) to the last quantifiable concentration (AUC0-t) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the AUC0-t of ALXN1920 following single ascending doses of ALXN1920.
Area under the concentration-time curve from time 0 (dosing) to time infinity (AUCinf) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the AUCinf of ALXN1920 following single ascending doses of ALXN1920.
Total body clearance (CL) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the CL of ALXN1920 following single ascending doses of ALXN1920.
Volume of distribution (Vd) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the Vd of ALXN1920 following single ascending doses of ALXN1920.
Amount of unchanged drug excreted in urine (Ae) Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose) To assess the Ae of ALXN1920 following single ascending doses of ALXN1920.
Maximum observed concentration (Cmax) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the Cmax of ALXN1920 following single ascending doses of ALXN1920.
Fraction of dose excreted in urine (fe) Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose) To assess the fe of ALXN1920 following single ascending doses of ALXN1920.
Terminal elimination half-life (t½) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the t½ of ALXN1920 following single ascending doses of ALXN1920.
Time to maximum observed concentration (tmax) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the tmax of ALXN1920 following single ascending doses of ALXN1920.
Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1920 Day 1 pre-dose and Day 29 post-dose To assess the immunogenicity to ALXN1920.
Terminal-phase elimination rate constant (λz) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the λz of ALXN1920 following single ascending doses of ALXN1920.
Apparent clearance (CL/F) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the CL/F of ALXN1920 following single ascending doses of ALXN1920.
Apparent volume of distribution (Vd/F) Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29 To assess the Vd/F of ALXN1920 following single ascending doses of ALXN1920.
Renal clearance (CLR) Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose) To assess the CLR of ALXN1920 following single ascending doses of ALXN1920.
Change in factor H Day 1 (Pre-dose, 0.5, 1 and 2 hours post-dose), post-dose on Day 2, 3, 4, 5, 8, 15, 22, and 29 To explore the PD effects of single ascending doses of ALXN1920. Change in factor H will be assessed using the factor H assay.
Change in complement alternative pathway (CAP) activity Day 1 (Pre-dose, 0.5, 1 and 2 hours post-dose), post-dose on Day 2, 3, 4, 5, 8, 15, 22, and 29 To explore the Pharmacodynamic (PD) effects of single ascending doses of ALXN1920. CAP activity will be assessed using the CAP hemolytic assay.
Geometric Mean Ratio (GMR) of Area Under the Curve (AUC) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1920 Day 29 post-dose To assess the absolute bioavailability of ALXN1920 SC.
Trial Locations
- Locations (2)
Research Site
🇳🇿Christchurch, New Zealand
Clinical Trial Site
🇳🇿Grafton, Auckland, New Zealand