Clinical trial NCT05259085: Study of ALXN2050 in Participants With Hepatic Impairment
Official title: A Phase 1, Open-Label, Multiple-Dose, Parallel Study to Determine the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of ALXN2050 in Adult Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Impaired Hepatic Function
Healthy
Keywords: Pharmacokinetics
Safety
Factor D inhibitor
ALXN2050
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-28
Enrollment: 26
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study will investigate the impact of impaired hepatic function (IHF) on the plasma pharmacokinetics of ALXN2050 in order to provide dosing recommendations for future indications in individuals with varying degrees of IHF.

Detailed description: The study will initiate (Part 1) with participants with mild IHF (Cohort 1) and moderate IHF (Cohort 2) and their matched healthy control participants (Cohort 4). Cohort 1 will be enrolled first, and following an adequate safety review, enrollment for Cohort 2 will begin. Following data review, the study may proceed (Part 2) with participants with severe IHF (Cohort 3) if deemed necessary.

Eligibility criteria: Inclusion Criteria:

1. Body weight must be at least 50.0 kilograms (kg) and body mass index (BMI) within the range of 18.0 - 40.0 kg/meter squared (inclusive) at the time of signing the informed consent.
2. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
3. Must agree to receive prophylactic antibiotics to mitigate the potential risk of meningococcal infection.

   Participants with Impaired Hepatic Function
4. Aside from IHF, sufficiently healthy for study participation based upon medical history, physical examination, neurological examination, laboratory tests, vital signs, and electrocardiograms (ECGs).
5. Score on the Child-Pugh scale at screening as follows:

   * Mild: Class A (Child-Pugh score ≥5 and ≤6); or
   * Moderate: Class B (Child-Pugh score ≥7 and ≤9); or
   * Severe: Class C (Child-Pugh score ≥10 and ≤15).
6. Diagnosis of chronic (\>6 months), stable (no acute episodes of illness within the previous 1 month due to deterioration in hepatic function) hepatic insufficiency.
7. Must be on a stable medication regimen. Concomitant medications must be approved by Alexion unless presented in the list of common concurrent medications for participants with IHF.
8. Cirrhosis, as evidenced by parenchymal liver disease by biopsy (histological diagnosis), imaging test, or other suitable imaging study, due to chronic hepatitis C virus (HCV) infection, chronic hepatitis B infection, cryptogenic, alcohol abuse, or non-alcoholic steatohepatitis.
9. No evidence of hepatocellular carcinoma as documented by imaging within 6 months prior to the first dose of study intervention.

   Matched Healthy Control Participants with Normal Hepatic Function
10. Must match the sex (similar ratio) and race (similar ratio of white and non-white) of participants with IHF; age must be within ± 10 years and BMI must be within ± 20% of participants with IHF at screening.
11. Healthy as determined by medical evaluation including medical history, physical examination, neurological examination, laboratory tests, vital signs, and ECGs.

Exclusion Criteria:

1. History or presence of seizures, head injury, head trauma, or any other brain disorder.
2. History of procedures that could alter absorption or excretion of orally administered drugs.
3. History of meningococcal infection or a first-degree relative with a history of meningococcal infection.
4. Body temperature ≥38.0°Celcius at screening or check-in or history of febrile illness or other evidence of infection, systemic or otherwise, within 14 days prior to the first dose of study intervention.
5. Classical pathway hemolysis results outside the reference ranges at screening, unless approved by Alexion.
6. Significant blood loss or donation of blood within 3 months prior to the first dose of study intervention, donation of plasma within 30 days prior to the first dose of study intervention, receipt of blood products within 6 months prior to first dose of study intervention, or receipt of a vaccine within 30 days prior to the first dose of study intervention.
7. Current enrollment or past participation within the last 30 days (or 5 half-lives, whichever is longer) prior to the first dose of study intervention in the current clinical study or any other clinical study involving an investigational study intervention or any other type of medical research.
8. Pregnant or lactating.
9. History or presence of drug or alcohol abuse within 6 months prior to the first dose of study intervention, current tobacco user, or positive results for alcohol and/or drug screen at screening or check-in.

Primary outcomes:
measure: Area Under The Concentration-time Curve From Time 0 To The 12-hour Time Point (AUC0-12) Of Plasma ALXN2050 After Steady-state
timeFrame: Up to 72 hours postdose
measure: Maximum (Peak) Steady-state Plasma Concentration Of ALXN2050 (Cmax,ss)
timeFrame: Up to 72 hours postdose
measure: Time To Reach Maximum (Peak) Plasma Concentration Following ALXN2050 Administration At Steady-state (Tmax,ss)
timeFrame: Up to 72 hours postdose
Secondary outcomes:
measure: Number Of Participants Receiving ALXN2050 With Treatment-emergent Adverse Events
timeFrame: Day 1 (postdose) through follow-up (30 [+/- 2] days after last study drug administration)
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
References: