A Study of Single and Multiple Doses of ALXN1210 in Healthy, Adult Japanese Participants
Condition: Healthy
Intervention: ALXN1210
Intervention description: Participants received a single dose (400 mg or 800 mg) and multiple doses (800 mg) of ALXN1210.
Intervention MeSH terms: Ravulizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ALXN1210; Pharmacokinetics; Pharmacodynamics; Safety; Immunogenicity

Summary:

      This study evaluated the safety and tolerability of single and multiple doses (400 and 800
      milligrams [mg]) of ALXN1210 following intravenous administration to healthy Japanese
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy Japanese males or females aged 25 through 55 years, inclusive (participants
             who lived outside of Japan for ≤ 10 years and were first-generation Japanese, defined
             as born in Japan and having 4 biological grandparents who were ethnic Japanese).

          -  Body mass index from 18 through 29.9 kilogram/square meter (kg/m^2), inclusive, with
             weight between 50 and 100 kg, inclusive.

          -  QT interval (corrected using the Fridericia's formula) ≤ 450 milliseconds (msec) for
             males and ≤ 470 msec for females at Screening and prior to dosing on Day 1.

          -  Willing and able to give written informed consent and comply with the study visit
             schedule

          -  Documented vaccination with tetravalent meningococcal conjugate vaccine (MCV4) at
             least 56 days and not more than 3 years prior to dosing. Documentation included a
             positive serum bactericidal assay to confirm an immune response before study drug
             administration.

          -  Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing on
             Day 1, with a booster administered at least 28 days prior to dosing on Day 1, with at
             least 28 days between the first and second injections.

          -  Female participants of childbearing potential were required to use highly effective
             contraception, starting at Screening and continuing until at least 6 months (Cohort 1)
             or 8 months (Cohorts 2 and 3) after the last dose of ALXN1210.

          -  Male participants with a female spouse/partner of childbearing potential or a pregnant
             or breastfeeding spouse or partner had to agree to use barrier contraception during
             the treatment period and for at least 6 months (Cohort 1) or 8 months (Cohorts 2 and
             3) after the last dose of ALXN1210.

        Exclusion Criteria:

          -  Participants who were in intimate and prolonged contact with (defined as living under
             the same roof or providing personal care) people younger than 2 years of age or older
             than 65 years of age, or who were either immunocompromised or had one of the following
             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); or human immunodeficiency virus (HIV).

          -  Participants who were professionals exposed to environments of greater risk for
             meningococcal disease; research, industrial, and clinical laboratory personnel
             routinely exposed to Neisseria meningitidis; military personnel during recruit
             training (military personnel may be at increased risk of meningococcal infection when
             accommodated in close quarters); daycare center workers; those who lived on a college
             or university campus; and those who planned to travel during the course of the study
             or have travelled to endemic areas for meningococcal meningitis (for example, India,
             Sub-Saharan Africa, pilgrimage to Saudi Arabia for Hajj) 6 months prior to dosing.

          -  History of any Neisseria infection

          -  History of unexplained, recurrent infection; or infection requiring treatment with
             systemic antibiotics within the 90 days prior to dosing.

          -  HIV infection (evidenced by HIV-1 or HIV-2 antibody titer)

          -  Acute or chronic hepatitis B virus infection. Hepatitis B surface antigen (HBsAg)
             testing was required for all participants prior to enrollment. Participants with
             positive HBsAg were not enrolled. For participants with negative HBsAg, the following
             testing algorithms were required: If hepatitis B core antibody (HBcAb) was negative,
             the participants was eligible to enroll and If HBcAb was positive, the hepatitis B
             surface antibody (HBsAb) was tested. (If both HBcAb and HBsAb were positive, the
             participants was eligible to enroll and If HBcAb was positive and HBsAb was negative,
             the participants was not enrolled.)

          -  Acute or chronic hepatitis C virus infection (evidenced by antibody titer)

          -  Active systemic viral or fungal infection 14 days prior to dosing.

          -  Positive or indeterminate QuantiFERON-TB test indicating possible tuberculosis
             infection.

          -  History of latent or active tuberculosis or exposure to endemic areas within 8 weeks
             prior to the Screening Visit.

          -  Female participants who were breastfeeding or were unwilling to practice contraception
             and were not postmenopausal.

          -  Positive serum pregnancy test at Screening or Day -1.

          -  Serum creatinine greater than the upper limit of normal (ULN) of the reference range
             of the testing laboratory at Screening or Day -1.

          -  Alanine aminotransferase or aspartate aminotransferase > ULN of the reference range of
             the testing laboratory at Screening or > 1.5*ULN of the reference range of the testing
             laboratory at Day -1.

          -  Any of the following hematology results: hemoglobin < 130 grams (g)/L for males and <
             115 g/L for females; hematocrit < 0.37 L/L for males and < 0.33 L/L for females; white
             blood cells < 3.0*10^3/microliter (μL); absolute neutrophils < 2.0*10^3/μL; and
             platelets < 150 or > 400*10^3/μL at Screening or Day -1; or complete blood count
             clinical laboratory results that were considered clinically relevant and unacceptable
             by the investigator at Day -1.

          -  History of complement deficiency or complement activity below normal reference range
             as evaluated by complement alternative pathway enzyme-linked immunosorbent assay at
             Screening.

          -  History of malignancy with the exception of a nonmelanoma skin cancer or carcinoma in
             situ of the cervix that had been treated with no evidence of recurrence.

          -  Participated in a clinical study within 30 days before initiation of dosing on Day 1
             or use of any experimental small-molecule therapy within 30 days prior to dosing on
             Day 1.

          -  Participated in more than 1 clinical study of a monoclonal antibody (mAb), or
             participation in a clinical study of an mAb within the 12 months prior to Screening,
             during which the participants was exposed to the active study drug. Participants who
             participated in only 1 study of an mAb could have been considered for enrollment if
             they completed that study more than 12 months prior to Screening.

          -  Major surgery or hospitalization within 90 days prior to dosing.

          -  Contraindication to receiving MCV4 and/or serogroup B vaccine, including severe
             allergic reaction to a previous dose of MCV4 and/or serogroup B vaccine; severe
             allergy to any vaccine component; or previous diagnosis of Guillain-Barré syndrome.

          -  History of allergy to excipients of ALXN1210 (for example, polysorbate 80)

          -  Documented history of penicillin or cephalosporin

          -  History of significant allergic reaction (anaphylaxis, or angioedema) to any product
             (for example, food and pharmaceutical).

          -  Smoked > 10 cigarettes daily (former smokers may have been permitted to enroll at the
             Investigator's discretion)

          -  Positive urine drug toxicology screen at Screening or Day -1.

          -  Donated plasma within 7 days prior to dosing. Donated or lost more than 50 mL of blood
             within 30 days of dosing or lost more than 499 mL of blood within 56 days of dosing

          -  Used prescription medications within 14 days prior to study drug administration.

          -  Clinical diagnosis of any autoimmune or rheumatologic disease.

          -  Immunized 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). Immunization with inactivated or recombinant influenza vaccine was
             permitted.

          -  Had fever (confirmed body temperature > 37.6°C) (for example, a fever associated with
             a symptomatic viral or bacterial infection) within 14 days prior to the first dosing.

          -  Participants with any medical history, conditions or risks which, in the opinion of
             the Investigator, may have interfered with the participant's full participation in the
             study, or compliance with the protocol, or posed any additional risk for the
             participant, or confounded the assessment of the participant or outcome of the study