A Study of a Single Dose of ALXN1210 in Healthy Participants
Condition: Healthy
Intervention: ALXN1210; Placebo
Intervention description: All doses of ALXN1210 were administered by IV infusion, using programmable IV infusion pump and IV sets with in-line filters, at a fixed rate of 686 mg/hour (equivalent to 137 milliliters [mL]/hour), excluding interruption for safety or technical reason.; All doses of placebo were administered by IV infusion, using programmable IV infusion pump and IV sets with in-line filters, at a fixed rate of 686 mg/hour (equivalent to 137 mL/hour), excluding interruption for safety or technical reason.
Intervention MeSH terms: Ravulizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Participants and on-site medical/nursing staff at the study site were blinded to study drug/dose assignment. The pharmacy staff preparing the investigational products, however, were not blinded to ALXN1210 study drug assignment, but all other site staff, including the Investigator, were blinded. Sponsor staff was unblinded as needed (for example, to participate in the Safety Review Committee and to determine reportability of serious adverse events [AEs]), but was to refrain from sharing any information on study drug assignment with the site staff.
Enrollment: 14.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ALXN1210; Pharmacokinetic; Pharmacodynamic; Safety; Immunogenicity

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).
    

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.