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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Biological: ALXN1920; Biological: ALXN1920; Biological: ALXN1920; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alexion Pharmaceuticals, Inc.; Phone Number: 1-855-752-2356; Email: clinicaltrials@alexion.com

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Actual): October 27, 2023
• Study Completion (Actual): December 4, 2023

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Pharmacodynamics; First-in-human; Single ascending dose; Sentinel dosing; Japanese Descent; ALXN1920
• Other Study ID Numbers: ALXN1920-HV-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No