Pharmacokinetic Study of Ravulizumab Administered Subcutaneously With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adult Volunteers
Condition: Healthy
Intervention: Ravulizumab; rHuPH20
Intervention description: Solution for infusion or injection, as applicable; Solution for infusion
Intervention MeSH terms: Ravulizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ALXN1210; Pharmacokinetic; Pharmacodynamic; Safety; Immunogenicity; Ravulizumab; rHuPH20

Summary:

      The main objectives of this study were to estimate the absolute bioavailability of
      ravulizumab/rHuPH20 subcutaneous (SC) and to assess the safety and tolerability of
      ravulizumab/rHuPH20 SC.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Body weight between 60 and 90 kilogram (kg), inclusive, and body mass index within the
             range 18 through 29.9 kg/square meter, inclusive.

          -  Negative serum pregnancy test at screening and Day -1

          -  Male participants and females 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) while on treatment and for up to 8 months after last dose of study
             drug.

          -  QT interval corrected using the Fridericia's formula (QTcF) ≤450 milliseconds (msec)
             for male participants and ≤470 msec for female participants at screening and prior to
             dosing on Day 1.

          -  Documented vaccination with meningococcal conjugate vaccine (MCV4) at least 56 days
             and not more than 2 years, 4 months prior to dosing.

          -  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.

        Key Exclusion Criteria:

          -  Current or recurrent disease (for example, cardiovascular, hematological,
             neurological, endocrine, immunological, rheumatological, renal, hepatic or
             gastrointestinal or other conditions) that or could affect clinical assessments or
             clinical laboratory evaluations.

          -  Current or relevant history of physical or psychiatric illness that are not stable or
             may require a change in treatment, use of prohibited therapies during the study or
             make the participant unlikely to fully comply with the requirements of the study or
             complete the study, or any condition that presents undue risk from the investigational
             product or study procedures.

          -  Any other significant disease or disorder which, in the opinion of the Investigator,
             may put the participant at risk.

          -  Documented history of allergy to penicillin or cephalosporin.

          -  History of significant allergic reaction (for example, anaphylaxis or angioedema) to
             any product (for example, food, pharmaceutical).

          -  Use of prescription medications (excluding oral contraceptives) within 14 days prior
             to dosing on Day 1, except with prior approval of the Sponsor.

          -  Regular use of nonprescription, over-the-counter medications, including herbal
             remedies and supplements, within 14 days prior to dosing on Day 1. Multivitamins,
             paracetamol (acetaminophen) ≤2 grams (g) per day, and topical skin products without
             significant systemic absorption are allowed.

          -  Positive urine drug toxicology screen at screening or on Day -1.

          -  Alcohol consumption within 48 hours prior to study drug administration or positive
             alcohol breath test on Day -1.

          -  Donation of plasma within 7 days prior to dosing on Day 1. Donation or loss (excluding
             volume drawn at screening) of more than 50 milliliters (mL) of blood within 30 days
             prior to dosing or more than 499 mL of blood within 56 days prior to dosing on Day 1.

          -  Female participants who are breastfeeding.

          -  Participants who are 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 are either immunocompromised or have 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 are one of the following:

               1. Professionals exposed to environments of greater risk for meningococcal disease

               2. Research, industrial, and clinical laboratory personnel who are routinely exposed
                  to N meningitidis

               3. Military personnel during recruit training

               4. Daycare center workers

               5. Those living on a college or university campus

               6. Those who plan to travel during the course of the study to or have travelled to
                  endemic areas for meningococcal meningitis (for example, India, Sub-Saharan
                  Africa, pilgrimage to Saudi Arabia for Hajj) within 6 months prior to dosing

          -  Immunization with a live-attenuated vaccine 28 days prior to dosing on Day 1 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
             is permitted.

          -  Prior exposure to ravulizumab or eculizumab.

          -  Major surgery or hospitalization within 90 days prior to dosing on Day 1.

          -  History of allergy or hypersensitivity to excipients of ravulizumab (for example,
             polysorbate 80), rHuPH20, or other hyaluronidases.

          -  Currently smokes >10 cigarettes daily (former smokers may be permitted to enroll at
             the Investigator's discretion) and is unwilling to refrain from smoking while a
             resident in the clinical research unit or comply with the smoking restrictions.

          -  History of illicit drug abuse, history of significant alcohol abuse within 1 year
             prior to the screening visit, or clinical evidence of substance and/or alcohol abuse
             within the 2 years before screening.