A Study of Multiple Doses of ALXN1210 in Healthy Adult Participants
Condition: Healthy
Intervention: ALXN1210; Placebo
Intervention description: ALXN1210 was administered by IV infusion over 5 periods, 1 dose per period: Period 1, induction; Periods 2-5, maintenance. Participants received a total of 5 doses of 400 or 800 mg, each administered every 28 days.; Placebo was administered by IV infusion over 5 periods, 1 dose per period. Participants received the same volume and infusion rate as specified for each ALXN1210 dose (400 or 800 mg).
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 who prepared ALXN1210 or placebo, however, was not blinded to study drug assignment, but all other site staff, including the Investigator and personnel administering study drug, was blinded. Sponsor staff was unblinded as needed (for example, to monitor the pharmacy), but did not share any information on study drug assignment with the site staff.
Enrollment: 16.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ALXN1210; Pharmacokinetics; Pharmacodynamics

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

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male and female participants ≥ 25 and ≤ 55 years old; smokers (no more than 10
             cigarettes daily), former smokers (at the Investigator's discretion), or nonsmokers.

          -  Body mass index from 18 through 29.9 kilogram (kg)/square meter, inclusive, and weight
             between 50 and 100 kg, inclusive.

          -  QT interval (corrected using the Fridericia formula) ≤ 450 milliseconds (ms) for males
             and ≤ 470 ms for females at Screening and prior to dosing on Day 1.

          -  Participant was 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 must have
             included a positive serum bactericidal antibody test to confirm an immune response
             before the study drug administration.

          -  Vaccination with serogroup B 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.

          -  Male participants with a female spouse/partner of childbearing potential or a pregnant
             or breastfeeding spouse or partner were required to use barrier contraception (male
             condom) during the treatment period and for at least 6 months after the last dose of
             ALXN1210.

        Exclusion Criteria:

          -  Participants who had intimate and prolonged contact (defined as living under the same
             roof or providing personal care) with individuals who were either immunocompromised,
             or had specific underlying medical conditions (persons with anatomic or functional
             asplenia [including sickle cell disease]; persons with congenital complement,
             properdin, factor D, or primary antibody deficiencies, persons with acquired
             complement deficiencies [for example, those receiving eculizumab], and persons with
             human immunodeficiency virus [HIV]) or with persons younger than 2 years of age or
             older than 65 years of age

          -  Participants who were one of the following: 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 when accommodated in
             close quarters); daycare center workers; those living on a college or university
             campus; or those who planned to travel during the course of the study to or had
             travelled to endemic areas for meningococcal meningitis (for example, India,
             Sub-Saharan Africa, pilgrimage to Saudi Arabia for Hajj) within the past 6 months

          -  History of any Neisseria infection

          -  History of unexplained recurrent infection or infection that required treatment with
             systemic antibiotics within the last 90 days prior to dosing

          -  HIV infection (evidenced by HIV-1 or HIV-2 antibody titer)

          -  Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B
             surface antigen or immunoglobulin M antibodies against hepatitis B core antigen)

          -  Acute or chronic hepatitis C virus infection (evidenced by antibody titer)

          -  Active systemic viral or fungal infection within 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 of childbearing potential,
             including any female who had experienced menarche and who had not undergone successful
             surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral
             oophorectomy) or who was pregnant, breastfeeding, or not postmenopausal.

          -  Positive serum pregnancy test at Screening or Day -1

          -  Serum creatinine > 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 < 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 reference
             range; absolute neutrophils < 1.5*10^3/μL (< 1.0*10^3/μL for black race participants)
             or > ULN of the testing laboratory reference range; and platelets < the lower limit of
             normal of the testing laboratory reference range or > 450*10^3/μL at Screening or Day
             -1; or complete blood count clinical laboratory results considered as 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, other than basal cell carcinoma that had been treated and had
             no evidence of recurrence.

          -  Participation 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.

          -  Participation in more than 1 clinical study of a monoclonal antibody (mAb) or
             participation in a clinical study of a mAb within the 12 months prior to Screening
             during which the participant was exposed to the active study drug. Participants who
             had participated in only 1 study of an mAb were considered for enrollment if they had
             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
             (life-threatening) allergic reaction to a previous dose of MCV4 and/or serogroup B
             vaccine, severe (life-threatening) allergy to any vaccine component, or previous
             diagnosis of Guillain-Barré syndrome.

          -  History of allergy to excipients of ALXN1210 (that is, polysorbate 80).

          -  Documented history of allergy to penicillin or cephalosporin.

          -  History of significant allergic reaction (anaphylaxis, angioedema) to any product
             (food, pharmaceutical, etc).

          -  Positive urine drug toxicology screen at Screening or Day -1.

          -  Donation of plasma within 7 days prior to dosing. Donation or loss (excluding volume
             drawn at Screening) of more than 50 mL of blood within 30 days of dosing or more than
             499 mL of blood within 56 days of dosing.

          -  Use of prescription medications within 28 days prior to study drug administration.

          -  Clinical diagnosis of any autoimmune or rheumatologic disease (for example, systemic
             lupus erythematosus, rheumatoid arthritis).

          -  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 (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 dose.

          -  Participants with any medical history, conditions or risks that, in the opinion of the
             Investigator, would have interfered with the participant's full participation in the
             study or compliance with the protocol, posed any additional risk for the participant,
             or confounded the assessment of the participant or outcome of the study.