Clinical trial NCT05288660: A Study of a Single Dose of ALXN1210 in Healthy Participants
Official title: A Phase 1, Randomized, Blinded, Placebo Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of ALXN1210 Administered Intravenously to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ALXN1210
Pharmacokinetic
Pharmacodynamic
Safety
Immunogenicity
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-21
Enrollment: 14
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single dose of ALXN1210 in healthy participants, as assessed by electrocardiograms, physical examination, vital signs, laboratory analysis, and assessment of adverse events (AEs).

Detailed description: The participants were randomized in a 2:1 ratio (4 active and 2 placebo) to receive a single dose of ALXN1210 or placebo in the 200-milligram (mg) dose cohort and in a 3:1 ratio (6 active and 2 placebo) to receive a single dose of ALXN1210 or placebo in the 400-mg dose cohort, administered by intravenous (IV) infusion. A 150-day observation period was performed for safety, pharmacokinetic, and pharmacodynamic assessments after study drug administration. Antidrug antibody (ADA) levels were monitored in study participants for the duration of the 150-day follow-up period.

Eligibility criteria: Inclusion Criteria:

* Body mass index from 18 through 29.9 kilogram (kg)/square meter, inclusive, and weight between 50 and 100 kg, inclusive.
* QT interval (Fridericia's correction); ≤450 milliseconds (msec) for males and ≤470 msec for females at screening and pre-dose on Day 1.
* Willing and able to give written informed consent and comply with the study visit schedule.
* Male participant and his female spouse/partner who was of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method), starting at screening and continuing until at least 5 months after the last dose of ALXN1210.
* Documented vaccination with meningococcal conjugate vaccine (MCV4) at least 14 days and not more than 3 years prior to dosing.

Exclusion Criteria:

* Participants in intimate and prolonged contact (defined as living under the same roof or providing personal care) with individuals who are either immunocompromised, or with a specific underlying medical conditions (anatomic or functional asplenia \[including sickle cell disease\]; congenital complement, properdin, factor D, or primary antibody deficiencies; acquired complement deficiencies \[for example, those receiving eculizumab\]; and human immunodeficiency virus \[HIV\]), people younger than 2 years old and older than 65 years old, and professionals exposed to environments of greater risk for meningococcal disease (research, industrial, and clinical laboratory personnel who are routinely exposed to Neisseria meningitidis, military personnel during recruit training \[military personnel may be at increased risk when accommodated in close quarters\], daycare center workers, or those living on a college or university campus).
* Participants living or working in the Saguenay-Lac-St-Jean area (due to increased incidence of meningococcal infections in that specific area).
* Female participants of childbearing potential, including any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or who was pregnant, breastfeeding, or was not postmenopausal.
* Positive serum pregnancy test at screening or Day -1.
* Serum creatinine greater than the upper limit of normal (ULN) of the testing laboratory at screening and Day -1.
* Alanine aminotransferase or aspartate aminotransferase \>ULN of the testing laboratory at screening and Day -1.
* Any of the following hematology tests: hemoglobin \<135 grams (g)/L for males and \<120 g/L for females; hematocrit \<0.41 L/L for males and \<0.36 L/L for females; white blood cells \<3.5\*10\^3/microliter (μL) or \>ULN of the testing laboratory; absolute neutrophils \<1.5\*10\^3/μL (\<1.0\*10\^3/μL for black race volunteers) or \>ULN of the testing laboratory; and platelets \<the lower limit of normal of the testing laboratory or \>450\*10\^3/μL at screening and Day -1.
* HIV infection (evidenced by HIV-1 or HIV-2 antibody titer).
* Acute or chronic hepatitis B virus (HBV) infection (evidenced by the presence of HBV surface antigen or immunoglobulin M antibodies against HBV core antigen).
* Acute or chronic hepatitis C virus infection (evidenced by antibody titer).
* Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
* Positive QuantiFERON-TB test, indicating possible tuberculosis (TB) infection.
* History of complement deficiency.
* History of malignancy other than basal cell carcinoma.
* Participated in a clinical trial within 30 days before initiation of dosing on Day 1, or used any experimental small-molecule therapy within 30 days prior to dosing on Day 1, or biologic therapy within 90 days prior to initiation of dosing on Day 1 or within 5 half-lives of the product, whichever is greater.
* Major surgery within the last 90 days prior to dosing.
* History of any Neisseria infection; history of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing.
* Contraindication to receiving MCV4, including severe (life-threatening) allergic reaction to a previous dose of MCV4; severe (life-threatening) allergy to any vaccine component; previous diagnosis of Guillain-Barré Syndrome.
* History of allergy to excipients of ALXN1210 (that is, polysorbate 80)
* History of allergy to penicillin or cephalosporin, or history of significant allergic reaction to other products (anaphylaxis and angioedema).
* Positive urine drug toxicology screen.
* Donation of plasma within 7 days prior to dosing. Donation or loss of blood of more than 50 mL of blood within 30 days of dosing, or more than 499 mL of blood within 56 days of dosing.
* Clinical diagnosis of any autoimmune or rheumatologic disease (for example, systemic lupus erythematosus, and rheumatoid arthritis) or other condition or medical history that, in the opinion of the Investigator, might interfere with the participant's participation in the study, poses an added risk for the participant, or confounds the assessment of the participant or outcome of the study.
* History of latent or active TB or exposure to endemic areas within 8 weeks prior to the TB test performed at screening.
* Immunization with a live attenuated vaccine 1 month prior to dosing or planned vaccination during the course of the study (except for the vaccination planned by the study protocol).
* Presence of fever (body temperature \> 37.6°C) (for example, a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to the first dosing.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 150
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Time To Maximum Observed Serum Concentration (Tmax) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Area Under The Serum Concentration Versus Time Curve From Time Zero To The Time of The Last Quantifiable Concentration (AUC0-t) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To Infinity (AUCinf) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Terminal Elimination Rate Constant (λz) of Serum ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Terminal Elimination Half-life (t½) of Serum ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Total Clearance (CL) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Volume of Distribution (Vd) of ALXN1210
timeFrame: Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150
measure: Percent Change From Baseline in Free Complement Component 5 (C5)
timeFrame: Baseline, Day 150
measure: Percent Change From Baseline in Total Complement C5
timeFrame: Baseline, Day 150
measure: Percent Change From Baseline in Complement C5b-9
timeFrame: Baseline, Day 8
measure: Percent Change From Baseline in Chicken Red Blood Cell Hemolysis
timeFrame: Baseline, Day 150
measure: Percent Change From Baseline In Complement Classical Pathway (CCP) Activity
timeFrame: Baseline, Day 150
measure: Percent Change From Baseline In Complement Alternative Pathway (CAP) Activity
timeFrame: Baseline, Day 150
measure: Percentage of Participants With Positive Anti-Drug Antibody (ADA)
timeFrame: Baseline up to Day 150
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Clinical Trial Site
Study officials:
References: