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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALXN1720 SC
* Drug: ALXN1720 IV
* Drug: rHuPH20
* Drug: Placebo SC
* Drug: Placebo IV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Pharmacodynamics, ALXN1720, Safety