Study of Subcutaneous and Intravenous ALXN1720 With and Without rHuPH20 in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT04920370
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ALXN1720 Single Dose IV ALXN1720 IV Participants will receive a single dose of ALXN1720 IV. ALXN1720 Multiple Dose SC ALXN1720 SC Participants will receive multiple doses of ALXN1720 SC. Placebo Placebo IV Participants will receive Placebo SC or Placebo IV according to their assigned cohort. ALXN1720 Single Dose SC ALXN1720 SC Participants will receive a single dose of ALXN1720 SC. ALXN1720 Single Dose SC + rHuPH20 ALXN1720 SC Participants will receive a single dose of ALXN1720 SC in combination with rHuPH20. Placebo Placebo SC Participants will receive Placebo SC or Placebo IV according to their assigned cohort. ALXN1720 Single Dose SC + rHuPH20 rHuPH20 Participants will receive a single dose of ALXN1720 SC in combination with rHuPH20.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-emergent and Serious Adverse Events (TEAEs, SAEs) Up to 176 days following the first day of dosing
- Secondary Outcome Measures
Name Time Method 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 Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity 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 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 Incidence of Antidrug Antibodies (ADAs) to ALXN1720 Up to 176 days following the first day of dosing Absolute Bioavailability of ALXN1720 Up to 176 days following the first day of dosing 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.
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 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
Trial Locations
- Locations (1)
Clinical Study Site
🇬🇧London, United Kingdom