A Study of a Single Subcutaneous Dose of ALXN1210 in Healthy Adult Participants
Condition: Healthy
Intervention: ALXN1210 SC; ALXN1210 IV; Placebo
Intervention description: All doses of ALXN1210 SC were administered by four 100-milligram (mg) SC injections of 1 milliliter (mL) each in the abdominal area. All four 1-mL injections were administered over a 15-minute period with at least 15 minutes between the end of injection in 1 participant and the start of injection in the next participant.; All doses of ALXN1210 IV were administered by IV infusion, using IV sets with in-line filters, at a maximum rate of 333 mL/hour, excluding interruption for safety or technical reason. There were at least 15 minutes between the end-of-infusion/injection in 1 participant and the start-of infusion/injection in the next participant.; All doses of placebo SC were administered by four 100-mg SC injections of 1 mL each in the abdominal area. All four 1-mL injections were administered over a 15-minute period with at least 15 minutes between the end of injection in 1 participant and the start of injection in the next participant.
Intervention MeSH terms: Ravulizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking description: This was a partially blinded study. During Cohorts 1a and 1b dosing, participants, study site medical/nursing staff, and other study site staff involved in the safety evaluations were blinded to study drug assignment. The pharmacy staff who prepared the SC injections and the research physician responsible for study drug administration was not blinded. In addition, a data manager responsible for masking some of the PK data was not blinded. Alexion staff were unblinded only on specific occasions (eg, to monitor that the SC injections were being prepared appropriately, to determine reportability of serious adverse events [AEs]), and refrained from sharing any information on study drug assignment with the study site staff. During Cohort 2, however, participants and study site staff were made aware of the treatment being administered.
Enrollment: 42.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetics; Pharmacodynamics; ALXN1210; Safety; Immunogenicity

Summary:

      This study evaluated the safety and tolerability of a single dose of ALXN1210 subcutaneous
      (SC) compared to ALXN1210 intravenous (IV) in healthy participants and to determine the
      absolute bioavailability of ALXN1210 SC.
    

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 corrected using Fridericia's formula ≤ 450 milliseconds (msec) for males
             and ≤ 470 msec for females at Screening and prior to dosing on Day 1.

          -  Was willing and was able to give written informed consent and complied with the study
             visit schedule.

          -  Documented vaccination with tetravalent meningococcal conjugate vaccine at least 56
             days and not more than 3 years prior to dosing. Documentation must have included a
             positive serum bactericidal antibody titer 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, if heterosexually active, must use
             highly effective contraception.

        Exclusion Criteria:

          -  Participants who were in intimate and prolonged contact with (defined as living under
             the same roof or providing personal care to) people younger than 2 years of age or
             older than 65 years of age, or who were either immunocompromised or had 1 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 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 could have been at increased risk of
             meningococcal infection when accommodated in close quarters); daycare center workers;
             those living on a college or university campus; and 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, or pilgrimage to Saudi Arabia for
             Hajj) within the past 6 months.

          -  History of any Neisseria infection.

          -  History of unexplained, recurrent infection, or infection requiring treatment with
             systemic antibiotics within 90 days prior to dosing.

          -  Evidence of HIV infection (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 algorithm was required: If hepatitis B core antibody (HBcAb) was negative, the
             participant 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 participant
             was eligible to enroll and If HBcAb was positive and HBsAb was negative, the
             participant was not enrolled.)

          -  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 which indicated possible tuberculosis
             (TB) infection.

          -  History of latent or active TB or exposure to endemic areas within 8 weeks prior to
             the Screening visit.

          -  Female participants who are breastfeeding or are heterosexually active and unwilling
             to practice contraception and are not postmenopausal.

          -  Positive serum pregnancy test at Screening or on Day -1.

          -  Serum creatinine greater than the upper limit of normal (ULN) of the reference range
             of the testing laboratory at Screening or on 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 on Day -1.

          -  Any of the following hematology results: hemoglobin < 130 grams (g)/liter for males
             and < 115 g/L for females, hematocrit < 0.37 L/L for males and < 0.33 L/L for females,
             white blood cell count < 3.0*10^3/microliter (μL), absolute neutrophil count <
             2.0*10^3/μL, and platelet count < 150 or > 400*10^3/μL at Screening or on Day -1.
             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 the 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.

          -  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 participants was exposed to the active study drug. Participants who
             participated in only 1 study of a mAb could have been considered for enrollment if
             they completed that study more than 12 months prior to screening.

          -  Prior exposure to ALXN1210.

          -  Major surgery or hospitalization within 90 days prior to dosing.

          -  History of allergy to excipients of ALXN1210 (for example, polysorbate 80).

          -  Documented history of allergy to penicillin or cephalosporin.

          -  History of significant allergic reaction (for example, anaphylaxis or angioedema) to
             any product (food, pharmaceutical, etc).

          -  Smoked > 10 cigarettes daily (former smokers could have been permitted to enroll at
             the Investigator's discretion).

          -  Positive urine drug toxicology screen at Screening or on 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 prior to dosing or more
             than 499 mL of blood within 56 days prior to dosing.

          -  Clinical diagnosis of any autoimmune or rheumatologic disease (for example, systemic
             lupus erythematosus, and rheumatoid arthritis).

          -  Immunization with a live-attenuated vaccine 28 days prior to dosing or planned
             vaccination during the course of the study (except for the vaccination planned per
             protocol). Immunization with inactivated or recombinant influenza vaccine was
             permitted.

          -  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
             dosing.

          -  Participants with any medical history, conditions, or risks that, in the opinion of
             the Investigator, could have interfered with the participant's full participation in
             the study or compliance with the protocol, or could have posed any additional risk for
             the participant or confounded the assessment of the participant or the outcome of the
             study.