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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Healthy Participants

Intervention / Treatment
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* Biological: ALXN1920
* Biological: Placebo
* Biological: ALXN1920
* Biological: ALXN1920


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by Subcutaneous (SC) injection.<br>|
| Experimental: Cohort 2<br>Participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by Subcutaneous (SC) injection.<br>|
| Experimental: Cohort 3<br>Participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by SC infusion.<br>|
| Experimental: Cohort 4<br>Participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by SC infusion.<br>|
| Experimental: Cohort 5<br>Participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by Intravenous (IV) infusion.<br>|
| Experimental: Cohort 6: Japanese Cohort<br>Japanese participants will receive a single dose of ALXN1920. | Biological: ALXN1920<br>* Participants will receive a single dose of ALXN1920 by SC infusion.<br>|
| Placebo Comparator: Pooled Placebo<br>Participants will receive Placebo. | Biological: Placebo<br>* Participants will receive a single dose of Placebo by SC injection, SC infusion or IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Terminal-phase elimination rate constant (λz) | To assess the λz 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-human, Single ascending dose, Sentinel dosing, ALXN1920, Safety, Pharmacokinetics, Pharmacodynamics, Japanese Descent