Clinical trial NCT04920370: Study of Subcutaneous and Intravenous ALXN1720 With and Without rHuPH20 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ALXN1720
Safety
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-emergent and Serious Adverse Events (TEAEs, SAEs)
timeFrame: Up to 176 days following the first day of dosing
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV
timeFrame: Up to 176 days following the first day of dosing
measure: Area Under The Concentration-time Curve (AUC) of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV
timeFrame: Up to 176 days following the first day of dosing
measure: Change from Baseline in Serum Concentrations of Free Complement Component 5 (C5)
timeFrame: Baseline, 176 days following the first day of dosing
measure: Change from Baseline in Serum Concentrations of Total C5
timeFrame: Baseline, 176 days following the first day of dosing
measure: Change from Baseline in Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity
timeFrame: Baseline, 176 days following the first day of dosing
measure: Incidence of Antidrug Antibodies (ADAs) to ALXN1720
timeFrame: Up to 176 days following the first day of dosing
measure: Absolute Bioavailability of ALXN1720
timeFrame: Up to 176 days following the first day of dosing
measure: Comparison of Incidence of TEAEs and SAEs Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Up to 176 days following the first day of dosing
measure: Comparison of Cmax of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Up to 176 days following the first day of dosing
measure: Comparison of AUC of ALXN1720 SC, ALXN1720 SC/rHuPH20, and ALXN1720 IV Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Up to 176 days following the first day of dosing
measure: Comparison of Change from Baseline in Serum Concentrations of Free C5 Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Baseline, 176 days following the first day of dosing
measure: Comparison of Change from Baseline in Serum Concentrations of Total C5 Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Baseline, 176 days following the first day of dosing
measure: Comparison of Change from Baseline in Serum Concentrations in Ex Vivo cRBC Hemolysis Activity Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Baseline, 176 days following the first day of dosing
measure: Comparison of ADAs to ALXN1720 Between Healthy Non-Japanese Participants and Participants of Japanese Descent
timeFrame: Up to 176 days following the first day of dosing
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Clinical Study Site
Study officials:
References: