Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1920 in Healthy Participants

Healthy Participants Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1920 in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05751642
• Other study ID #: ALXN1920-HV-101
• Status: Completed
• Phase: Phase 1
• Start date: April 24, 2023
• Est. completion date: December 4, 2023

Study information

• Verified date: December 2023
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 4, 2023
• Est. primary completion date: October 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Biological:
• ALXN1920
Participants will receive a single dose of ALXN1920 by Subcutaneous (SC) injection.
• Placebo
Participants will receive a single dose of Placebo by SC injection, SC infusion or IV infusion.
• ALXN1920
Participants will receive a single dose of ALXN1920 by SC infusion.
• ALXN1920
Participants will receive a single dose of ALXN1920 by Intravenous (IV) infusion.

Locations

Country	Name	City	State
New Zealand	Clinical Trial Site	Grafton	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse events (AEs)	To assess the safety and tolerability of single ascending doses of ALXN1920.	Up to End of study visit (Day 29)
Secondary	Maximum observed concentration (Cmax)	To assess the Cmax of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Time to maximum observed concentration (tmax)	To assess the tmax of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Area under the concentration-time curve from time 0 (dosing) to the last quantifiable concentration (AUC0-t)	To assess the AUC0-t of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Area under the concentration-time curve from time 0 (dosing) to time infinity (AUCinf)	To assess the AUCinf of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Terminal elimination half-life (t½)	To assess the t½ of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Terminal-phase elimination rate constant (?z)	To assess the ?z of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Total body clearance (CL)	To assess the CL of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Apparent clearance (CL/F)	To assess the CL/F of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Volume of distribution (Vd)	To assess the Vd of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Apparent volume of distribution (Vd/F)	To assess the Vd/F of ALXN1920 following single ascending doses of ALXN1920.	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
Secondary	Renal clearance (CLR)	To assess the CLR of ALXN1920 following single ascending doses of ALXN1920.	Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
Secondary	Amount of unchanged drug excreted in urine (Ae)	To assess the Ae of ALXN1920 following single ascending doses of ALXN1920.	Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
Secondary	Fraction of dose excreted in urine (fe)	To assess the fe of ALXN1920 following single ascending doses of ALXN1920.	Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
Secondary	Change in complement alternative pathway (CAP) activity	To explore the Pharmacodynamic (PD) effects of single ascending doses of ALXN1920. CAP activity will be assessed using the CAP hemolytic assay.	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
Secondary	Change in factor H	To explore the PD effects of single ascending doses of ALXN1920. Change in factor H will be assessed using the factor H assay.	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
Secondary	Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1920	To assess the immunogenicity to ALXN1920.	Day 1 pre-dose and Day 29 post-dose
Secondary	Geometric Mean Ratio (GMR) of Area Under the Curve (AUC) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1920	To assess the absolute bioavailability of ALXN1920 SC.	Day 29 post-dose