A Study of Multiple Doses of ALXN2050 in Healthy Adults

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN2050; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1: 40 mg ALXN2050/Placebo; Participants randomized to receive ALXN2050 or placebo twice daily (BID) on Day 1 through Day 14 in a fasted state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.
EXPERIMENTAL: Cohort 2: 80 mg ALXN2050/Placebo; Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.
EXPERIMENTAL: Cohort 3: 120 mg ALXN2050/Placebo; Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.
EXPERIMENTAL: Cohort 4: 200 mg ALXN2050/Placebo; Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.
EXPERIMENTAL: Cohort 5: 120 mg ALXN2050/Placebo; Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fed state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.
EXPERIMENTAL: Cohort 6: 240 mg ALXN2050/Placebo; Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fasted state.	Drug: ALXN2050; Powder-in-capsule (PIC).; Other Names: ACH-0145228 (formerly); ACH-5228; Drug: Placebo; PIC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Achillion, a wholly owned subsidiary of Alexion

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 7, 2019
• Primary Completion (ACTUAL): July 23, 2019
• Study Completion (ACTUAL): July 23, 2019

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (ACTUAL): September 17, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Complement; Pharmacodynamics; Factor D Inhibitor; ALXN2050; ACH-0145228
• Other Study ID Numbers: ACH228-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No