Clinical trial NCT05751642: Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1920 in Healthy Participants
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1920 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: First-in-human
Single ascending dose
Sentinel dosing
ALXN1920
Safety
Pharmacokinetics
Pharmacodynamics
Japanese Descent
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse events (AEs)
timeFrame: Up to End of study visit (Day 29)
Secondary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: 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
measure: Time to maximum observed concentration (tmax)
timeFrame: 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
measure: Area under the concentration-time curve from time 0 (dosing) to the last quantifiable concentration (AUC0-t)
timeFrame: 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
measure: Area under the concentration-time curve from time 0 (dosing) to time infinity (AUCinf)
timeFrame: 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
measure: Terminal elimination half-life (t½)
timeFrame: 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
measure: Terminal-phase elimination rate constant (λz)
timeFrame: 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
measure: Total body clearance (CL)
timeFrame: 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
measure: Apparent clearance (CL/F)
timeFrame: 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
measure: Volume of distribution (Vd)
timeFrame: 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
measure: Apparent volume of distribution (Vd/F)
timeFrame: 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
measure: Renal clearance (CLR)
timeFrame: Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
measure: Amount of unchanged drug excreted in urine (Ae)
timeFrame: Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
measure: Fraction of dose excreted in urine (fe)
timeFrame: Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose)
measure: Change in complement alternative pathway (CAP) activity
timeFrame: 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
measure: Change in factor H
timeFrame: 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
measure: Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1920
timeFrame: Day 1 pre-dose and Day 29 post-dose
measure: Geometric Mean Ratio (GMR) of Area Under the Curve (AUC) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1920
timeFrame: Day 29 post-dose
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: Clinical Trial Site
state: Auckland
city: Christchurch
country: New Zealand
facility: Research Site
Study officials:
References: