A Study of Multiple Doses of ALXN2050 in Healthy Adults

Study Overview
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Brief Summary
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This was a Phase 1, placebo-controlled, randomized, double-blind (participant and investigator blind, sponsor open), multiple-ascending dose study conducted in healthy participants to demonstrate the safety and tolerability and to evaluate the pharmacokinetics and pharmacodynamics of ACH-0145228 (ALXN2050).

Official Title
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A Randomized, Double-Blind, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACH-0145228 in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALXN2050
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Was overtly healthy as determined by medical evaluation including detailed medical history, physical examination, blood pressure and heart rate measurements, 12-lead ECG, and clinical laboratory tests. Had a body weight of at least 50 kilograms (kg) and body mass index within the range of 18 to 30 kg/meter squared (inclusive). Male participants were eligible to participate if they agreed to abstinence or use of a highly effective method of contraception. Female participants must have been of nonchildbearing potential. Key Exclusion Criteria: Had a history or clinically relevant evidence of current cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disorders or conditions capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. Had a body temperature greater than or equal to 38°Celsius on Day -1 or Day 1, Hour 0; had a history of febrile illness, or other evidence of infection, within 14 days prior to first study drug administration. Had a sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicated participation in the study. Donated blood or lost more than 500 milliliters of blood within 3 months prior to first study drug administration, or received a blood transfusion or blood products within 6 months prior to first study drug administration. Current enrollment or past participation within the last 30 days before study drug administration in any clinical study involving an investigational study intervention or any other type of medical research Had clinically significant laboratory abnormalities. Positive urine drug screen at Screening or Day -1; was a current tobacco/nicotine user or smoker; consumed any alcohol within 72 hours before first study drug administration or had a history of regular alcohol consumption within 6 months of screening.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 40 mg ALXN2050/Placebo<br>Participants randomized to receive ALXN2050 or placebo twice daily (BID) on Day 1 through Day 14 in a fasted state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|
| Experimental: Cohort 2: 80 mg ALXN2050/Placebo<br>Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|
| Experimental: Cohort 3: 120 mg ALXN2050/Placebo<br>Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|
| Experimental: Cohort 4: 200 mg ALXN2050/Placebo<br>Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|
| Experimental: Cohort 5: 120 mg ALXN2050/Placebo<br>Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fed state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|
| Experimental: Cohort 6: 240 mg ALXN2050/Placebo<br>Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fasted state. | Drug: ALXN2050<br>* Powder-in-capsule (PIC).<br>* Other names: ACH-5228;Drug: Placebo<br>* PIC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Experiencing Serious Adverse Events |  | Day 1 through Day 42 | 
| Number Of Participants Experiencing Grade 3 Or 4 Adverse Events (AEs) |  | Day 1 through Day 42 | 
| Number Of Participants Experiencing AEs Leading To Discontinuation From The Study |  | Day 1 through Day 42 | 
| Number Of Participants Experiencing Grade 3 Or 4 Laboratory Abnormalities |  | Day 1 through Day 42 | 
| Number Of Participants Experiencing Treatment-emergent Vital Signs, Physical Examination Results, And Electrocardiogram (ECG) Abnormalities |  | Day 1 through Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Steady-state Plasma Concentration (Cmax,ss) Of Multiple-dose ALXN2050 |  | Up to 168 hours postdose | 
| Time To Reach Maximum Steady-state Plasma Concentration (Tmax,ss) Of Multiple-dose ALXN2050 |  | Up to 168 hours postdose | 
| Area Under The Plasma Concentration Versus Time Curve Over The Dosing Interval (AUCtau) Of Multiple-dose ALXN2050 |  | Up to 168 hours postdose | 
| Maximum Plasma Concentration (Cmax) Of Single-dose ALXN2050 |  | Up to 72 hours postdose | 
| Time To Reach Maximum Plasma Concentration (Tmax) Of Single-dose ALXN2050 |  | Up to 72 hours postdose | 
| Area Under The Concentration-time Curve Extrapolated To Infinity (AUC0-inf) For Single-dose ALXN2050 |  | Up to 72 hours postdose | 
| Alternative Pathway (AP) Activity As Measured By Wieslab Assay |  | Up to 14 days postdose | 
| Plasma Bb Fragment Of Complement Factor B Concentration Over Time |  | Up to 14 days postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor D Inhibitor, Complement, ALXN2050, ACH-0145228, Pharmacokinetics, Pharmacodynamics, Safety