Safety, PK/PD, and Immunogenicity Study of SC ALXN2030 in Healthy Participants

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety and tolerability of single ascending doses of ALXN2030 in healthy participants.

Detailed Description
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Approximately 48 healthy adult participants (8 of whom being Japanese; 36 on ALXN2030, 12 on placebo) are expected to be enrolled. Japanese participants will receive Dose E.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Subcutaneous ALXN2030 in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALXN2030
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants QTcF ≤ 450 msec at Screening and on admission (ie, on Day -1). Participants of Japanese descent are defined as: First generation (born to 2 Japanese parents and 4 Japanese grandparents). Participants of Japanese descent must be between 20 and 60 years of age. BMI within the range 18-32kg/m2 (inclusive) at Screening. Exclusion Criteria: Current or recurrent disease Current or relevant history of physical or psychiatric illness. Any other significant disease or disorder that, in the opinion of the Investigator, may put the participant at risk. Female participants who are pregnant or breastfeeding. Major surgery or hospitalization within 90 days prior to dosing on Day1. History of allergy or hypersensitivity to an oligonucleotide or GalNAc moiety or any excipients of ALXN2030.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN2030 Dose A<br>ALXN2030 will be administered as a manual subcutaneous (SC) injection. | Drug: ALXN2030<br>* ALXN2030 will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|
| Experimental: ALXN2030 Dose B<br>ALXN2030 will be administered as a manual SC injection. | Drug: ALXN2030<br>* ALXN2030 will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|
| Experimental: ALXN2030 Dose C<br>ALXN2030 will be administered as a manual SC injection. | Drug: ALXN2030<br>* ALXN2030 will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|
| Experimental: ALXN2030 Dose D<br>ALXN2030 will be administered as a SC infusion via a syringe pump. | Drug: ALXN2030<br>* ALXN2030 will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|
| Experimental: ALXN2030 Dose E<br>ALXN2030 will be administered as a SC infusion via a syringe pump. | Drug: ALXN2030<br>* ALXN2030 will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered as a manual SC injection or as a SC infusion via a syringe pump, depending on dose. | Drug: Placebo<br>* Placebo will be administered subcutaneously as a single dose either as a manual SC injection or as an SC infusion via a syringe pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |  | Day 1 through end of study (up to Day 127) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Days 1 (predose; end of infusion (EOI); and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours post-EOI), 2, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, and 127 | 
| Time to Maximum Observed Plasma Concentration (Tmax) |  | Days 1 (predose; EOI; and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours post-EOI), 2, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, and 127 | 
| Area Under the Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) |  | Days 1 (predose; EOI; and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours post-EOI), 2, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, and 127 | 
| Change from Baseline in Plasma Concentration of Complement Component 3 (C3) Protein |  | Baseline (Day 1) and Day 127 | 
| Change from Baseline in Serum Complement Functional Activity |  | Baseline (Day 1) and Day 127 | 
| Number of Participants With Treatment-Emergent Antidrug Antibodies (ADAs) |  | Days 1 through Day 127 |