Study of ALXN1820 in Healthy Adult Participants

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study of Subcutaneous and Intravenous ALXN1820 in Healthy Participants

This is a Phase 1, randomized, double-blind, placebo-controlled single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN1820 administered subcutaneously (SC) (ALXN1820 SC) and intravenously (IV) (ALXN1820 IV).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN1820 SC; Drug: ALXN1820 IV; Drug: Placebo SC; Drug: Placebo IV

Detailed Description

This study will include up to 10 different dosing cohorts, with each cohort consisting of 2 groups (ALXN1820 group, placebo group). Participants will be randomly assigned in a 3:1 ratio to each of these 2 groups, respectively, within all 10 cohorts, to receive either a single or multiple doses of ALXN1820 SC, a single dose of ALXN1820 IV, or a single or multiple doses of placebo.

The study will be conducted in healthy adult participants and will also include a multiple SC dose cohort in healthy participants of Japanese descent.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4006
    • Clinical Study Site
• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body weight 50 to 100 kilograms (kg); body mass index 17 to 32 kg/meter squared.
• Cohort 9 only: Japanese participants (defined as those participants whose parents and grandparents are both Japanese and who have spent less than 5 years outside of Japan).
• Satisfactory medical assessment.
• Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose.

• Vaccination requirement:

  • Vaccination with tetravalent meningococcal conjugate vaccine at least 56 days and not more than 2 years, 6 months prior to dosing;
  • Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing, with a booster at least 28 days prior to dosing, with at least 28 days between the first and second injections.

Exclusion Criteria:

• Current/recurrent diseases or relevant medical history.
• History of any Neisseria infection.
• Hepatitis B/C, human immunodeficiency virus.
• History of latent or active tuberculosis (TB), or positive TB test.
• Active systemic infection within 14 days of dosing.
• Risk of meningococcal infections due to living/working conditions.
• History of complement deficiency or complement activity below the reference range.
• Participation in a clinical study within 90 days or 5 half lives of the investigational agent (whichever is longer) before initiation of dosing on Day 1.
• Participation in more than 1 clinical study of a monoclonal antibody (mAb), or participation in a clinical study of a mAb within the 6 months or 5 half lives of the mAb (whichever is longer) prior to screening.
• Acquired complement deficiencies (for example, those receiving eculizumab).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1820; Participants will receive ALXN1820 SC or ALXN1820 IV according to their assigned cohort. ALXN1820 SC will be evaluated in single and multiple ascending doses while ALXN1820 IV will be evaluated in a single dose cohort only.	Drug: ALXN1820 SC; ALXN1820 SC will be administered as a manual SC push or SC infusion via a syringe pump. Doses will range from 12.5 milligrams (mg) to a maximum of 2250 mg. Multiple dosing duration will range from 3 to 5 weeks.; Drug: ALXN1820 IV; ALXN1820 IV (450 mg) will be administered as an IV infusion.
Placebo Comparator: Placebo; Participants will receive Placebo SC or Placebo IV according to their assigned cohort.	Drug: Placebo SC; Placebo SC will be administered as a manual SC push or SC infusion via a syringe pump.; Drug: Placebo IV; Placebo IV will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV	An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as any AEs that commenced after the start of administration of study intervention. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported AEs' Section.	Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts		Up to 126 days following the first day of dosing
Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts		Up to 154 days following the first day of dosing
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts		Up to 126 days following the first day of dosing
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts		Up to 154 days following the first day of dosing
Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts		Baseline, Day 127
Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts		Baseline, Day 127
Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts		Baseline, Day 127
Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV		Baseline up to Day 155
Absolute Bioavailability Of ALXN1820 SC	The absolute bioavailability was expressed as ratio and was calculated as the geometric mean for the AUC[0-inf] for SC divided by the geometric mean for the AUC[0-inf] for IV. Least square means were calculated with cohort, treatment, and sequence as the fixed effects, and participant-participant (sequence) as a random effect.	Baseline up to Day 127

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Syneos Health

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2021
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; ALXN1820; Properdin
• Other Study ID Numbers: ALXN1820-HV-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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