Study of Subcutaneous and Intravenous ALXN1720 With and Without rHuPH20 in Healthy Subjects

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study of Subcutaneous and Intravenous ALXN1720 With and Without rHuPH20 in Healthy Subjects

This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN1720 administered subcutaneously (SC) or intravenously (IV).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN1720 SC; Drug: rHuPH20; Drug: ALXN1720 IV; Drug: Placebo SC; Drug: Placebo IV

Detailed Description

Participants will be randomized in a 3:1 ratio to receive the active treatment or placebo.

The study will be conducted in healthy adult participants, including participants of Japanese descent.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body weight within 50 to 90 kilograms (kg), inclusive, and body mass index within the range of 18 to 29.9 kg/meter squared, inclusive.
• Willing to follow protocol-specified contraception guidance while on treatment and for 6 months after the last dose of study treatment.
• Vaccination with tetravalent meningococcal conjugate vaccine and serogroup B meningococcal vaccine.
• No clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory evaluation.
• For the cohorts with Japanese participants, parents and grandparents must both be Japanese, and participants must have resided for less than 5 years outside of Japan.

Exclusion Criteria:

• Current or recurrent disease that could affect clinical assessments or clinical laboratory evaluations.
• History of complement deficiency or complement activity below the reference range.
• Female participants who are breastfeeding.
• Immunization with a live-attenuated vaccine 28 days prior to dosing on Day 1 or planned vaccination during the course of the study. Immunization with inactivated or recombinant influenza vaccine, or nucleoside-modified messenger ribonucleic acid or recombinant COVID-19 vaccine is permitted.
• Current tobacco smoking, history of illicit drug abuse, or history of significant alcohol abuse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive Placebo SC or Placebo IV according to their assigned cohort.	Drug: Placebo SC; Placebo will be administered via SC route.; Drug: Placebo IV; Placebo will be administered via IV route.
Experimental: ALXN1720 Single Dose SC; Participants will receive a single dose of ALXN1720 SC.	Drug: ALXN1720 SC; ALXN1720 will be administered via SC route.
Experimental: ALXN1720 Multiple Dose SC; Participants will receive multiple doses of ALXN1720 SC.	Drug: ALXN1720 SC; ALXN1720 will be administered via SC route.
Experimental: ALXN1720 Single Dose SC + rHuPH20; Participants will receive a single dose of ALXN1720 SC in combination with rHuPH20.	Drug: ALXN1720 SC; ALXN1720 will be administered via SC route.; Drug: rHuPH20; rHuPH20 will be administered via SC route.
Experimental: ALXN1720 Single Dose IV; Participants will receive a single dose of ALXN1720 IV.	Drug: ALXN1720 IV; ALXN1720 will be administered via IV route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-emergent and Serious Adverse Events (TEAEs, SAEs)	Up to 176 days following the first day of dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV		Up to 176 days following the first day of dosing
Area Under The Concentration-time Curve (AUC) of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV		Up to 176 days following the first day of dosing
Change from Baseline in Serum Concentrations of Free Complement Component 5 (C5)		Baseline, 176 days following the first day of dosing
Change from Baseline in Serum Concentrations of Total C5		Baseline, 176 days following the first day of dosing
Change from Baseline in Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity		Baseline, 176 days following the first day of dosing
Incidence of Antidrug Antibodies (ADAs) to ALXN1720		Up to 176 days following the first day of dosing
Absolute Bioavailability of ALXN1720	The absolute bioavailability for ALXN1720 SC will be defined by the ratio of the geometric means for AUC for ALXN1720 SC over ALXN1720 IV after a single dose.	Up to 176 days following the first day of dosing
Comparison of Incidence of TEAEs and SAEs Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Up to 176 days following the first day of dosing
Comparison of Cmax of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Up to 176 days following the first day of dosing
Comparison of AUC of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Up to 176 days following the first day of dosing
Comparison of Change from Baseline in Serum Concentrations of Free C5 Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Baseline, 176 days following the first day of dosing
Comparison of Change from Baseline in Serum Concentrations of Total C5 Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Baseline, 176 days following the first day of dosing
Comparison of Change from Baseline in Serum Concentrations in Ex Vivo cRBC Hemolysis Activity Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Baseline, 176 days following the first day of dosing
Comparison of ADAs to ALXN1720 Between Healthy Non-Japanese Participants and Participants of Japanese Descent		Up to 176 days following the first day of dosing

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Actual): November 16, 2021
• Study Completion (Actual): November 16, 2021

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Pharmacodynamics; ALXN1720
• Other Study ID Numbers: ALXN1720-HV-101; 2018-004500-19 (EudraCT Number)

Drug and device information, study documents

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