Pharmacokinetic Study of Ravulizumab Administered Subcutaneously With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adult Volunteers

NCT ID: NCT05396742

Last Updated: 2024-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-09
• Study Completion Date: 2019-05-21

Brief 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cohort 1

Participants received a single dose of ravulizumab SC 400 (milligrams) mg .

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: DRUG

Solution for infusion or injection, as applicable

Cohort 2

Participants received a single dose of ravulizumab SC 500 mg/rHuPH20 10000 units.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: DRUG

Solution for infusion or injection, as applicable

rHuPH20

Intervention Type: DRUG

Solution for infusion

Cohort 3

Participants received a single dose of ravulizumab SC 1000 mg/rHuPH20 20000 units.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: DRUG

Solution for infusion or injection, as applicable

rHuPH20

Intervention Type: DRUG

Solution for infusion

Cohort 4

Participants received a single dose of ravulizumab SC 2000 mg/rHuPH20 40000 units.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: DRUG

Solution for infusion or injection, as applicable

rHuPH20

Intervention Type: DRUG

Solution for infusion

Cohort 5

Participants received a single dose of ravulizumab intravenously (IV) 400 mg.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: DRUG

Solution for infusion or injection, as applicable

Interventions

Ravulizumab

Solution for infusion or injection, as applicable

Intervention Type: DRUG

rHuPH20

Solution for infusion

Intervention Type: DRUG

Other Intervention Names

Ultomiris; ALXN1210; Recombinant human hyaluronidase PH20

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Trial Site

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004931-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-HV-105

Identifier Type: -

Identifier Source: org_study_id