Study of ALXN2050 in Participants With Renal Impairment

Healthy Clinical Trial

Official title:

A Phase 1, Open-Label, Multiple-Dose, Parallel Study to Determine the Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ALXN2050 in Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04623710
• Other study ID #: ALXN2050-HV-108
• Status: Completed
• Phase: Phase 1
• Start date: July 8, 2021
• Est. completion date: March 21, 2022

Study information

• Verified date: September 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the impact of impaired renal function on the plasma pharmacokinetics of ALXN2050 in order to provide dosing recommendations for future indications in individuals with impaired renal function.

Description:

The study will initiate (Part 1) with participants with severe impaired renal function (Cohort 1) and their matched healthy control participants (Cohort 4). Following data review, the study may proceed (Part 2) with participants with moderate (Cohort 2) and mild (Cohort 3) impaired renal function if deemed necessary.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 21, 2022
• Est. primary completion date: February 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 (m^2) (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 Renal Function

4. Aside from impaired renal function, sufficiently healthy for study participation based upon medical history, physical examination, neurological examination, laboratory tests, vital signs, and electrocardiograms (ECGs).

5. A clinical diagnosis of impaired stable renal function.

6. No clinically significant change in renal status at least 1 month prior to first dose of study intervention and is not currently or has not previously been on hemodialysis or did not have any history of peritoneal dialysis.

7. Stable creatinine clearance.

8. 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 impaired renal function.

Matched Healthy Control Participants with Normal Renal Function

9. Must match the sex and the race (similar ratio of white and non-white) of participants with impaired renal function, and at screening, age must be within ± 10 years and BMI must be within ± 20% of the matching participants with impaired renal function

10. Healthy as determined by medical evaluation, including medical history, physical examination, neurological examination, laboratory tests, vital signs, and ECGs, and who possess a baseline eGFR = 90 mL/min/1.73 m^2, based on MDRD equation at screening.

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. Participants with CH50 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. History or presence of drug or alcohol abuse within 1 year 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.

9. Pregnant or lactating.

10. Does not produce sufficient urine output to permit urine sampling at screening and/or check-in or has a history of urinary incontinence prior to check-in.

11. History of kidney transplant or actively on a transplant waiting list prior to check-in.

12. Any acute or chronic non-renal condition prior to check-in that would limit the participant's ability to complete or participate in this clinical study.

Related Conditions & MeSH terms

• Healthy
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• ALXN2050
ALXN2050 (120 milligrams) will be administered orally twice daily on Days 1 through 3, with an additional dose (120 milligrams) administered orally on the morning of Day 4.

Locations

Country	Name	City	State
United States	Clinical Trial Site	Hialeah	Florida
United States	Clinical Trial Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under The Concentration-time Curve From Time 0 To The 12-hour Time Point (AUC0-12) Of Plasma ALXN2050 After Steady-state		Up to 72 hours postdose
Primary	Area Under The Concentration-time Curve Calculated To The Last Observable Concentration At Time t (AUCt) Of Plasma ALXN2050 After Steady-state		Up to 72 hours postdose
Primary	Maximum (Peak) Steady-state Plasma Concentration (Cmax,ss) Of Plasma ALXN2050		Up to 72 hours postdose
Primary	Time To Reach Maximum (Peak) Plasma Concentration Following ALXN2050 Administration At Steady-state (Tmax,ss)		Up to 72 hours postdose
Secondary	Change From Baseline In Complement Factor D Concentration At 24, 48, And 72 Hours Postdose		Baseline, 24, 48, and 72 hours postdose
Secondary	Change From Baseline In Plasma b Fragment Of Complement Factor B Concentration		Baseline, up to 72 hours postdose
Secondary	Change From Baseline In Complement Alternative Pathway Activity		Baseline, up to 72 hours postdose
Secondary	Number Of Participants Receiving ALXN2050 With Treatment-emergent Adverse Events		Day 1 (postdose) through follow-up (30 [+/- 2] days after last study drug administration)]