- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05396742
Pharmacokinetic Study of Ravulizumab Administered Subcutaneously With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adult Volunteers
April 28, 2023 updated by: Alexion Pharmaceuticals, Inc.
A Partially Randomized, Sequential Cohort, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Subcutaneous Ravulizumab Coadministered With rHuPH20 in Healthy Adult Volunteers
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
49
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
London, United Kingdom
- Clinical Trial Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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:
- Professionals exposed to environments of greater risk for meningococcal disease
- Research, industrial, and clinical laboratory personnel who are routinely exposed to N meningitidis
- Military personnel during recruit training
- Daycare center workers
- Those living on a college or university campus
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1
Participants received a single dose of ravulizumab SC 400 (milligrams) mg .
|
Solution for infusion or injection, as applicable
Other Names:
|
Experimental: Cohort 2
Participants received a single dose of ravulizumab SC 500 mg/rHuPH20 10000 units.
|
Solution for infusion or injection, as applicable
Other Names:
Solution for infusion
Other Names:
|
Experimental: Cohort 3
Participants received a single dose of ravulizumab SC 1000 mg/rHuPH20 20000 units.
|
Solution for infusion or injection, as applicable
Other Names:
Solution for infusion
Other Names:
|
Experimental: Cohort 4
Participants received a single dose of ravulizumab SC 2000 mg/rHuPH20 40000 units.
|
Solution for infusion or injection, as applicable
Other Names:
Solution for infusion
Other Names:
|
Experimental: Cohort 5
Participants received a single dose of ravulizumab intravenously (IV) 400 mg.
|
Solution for infusion or injection, as applicable
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20
Time Frame: Day 1 (after first dose) to Day 200
|
Dose-normalized area under the serum concentration versus time curve from 0 extrapolated to infinity (AUC0-inf) and body weight-adjusted AUC0-inf for the ravulizumab/rHuPH20 SC cohorts were compared with the 400 mg ravulizumab intravenous (IV) cohort to determine absolute bioavailability.
Geometric mean ratios of the AUC0-inf parameter were calculated for each group.
Absolute bioavailability is reported as the geometric mean ratio, which was defined as the ratio of geometric means for the dose-normalized AUC0-inf parameter (with and without body-weight adjustment) for the ravulizumab SC cohort divided by that for the ravulizumab IV cohort.
|
Day 1 (after first dose) to Day 200
|
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Day 1 (after first dose) up to Day 200 (including safety follow up)
|
An AE was reported as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug.
Serious AEs (SAEs) were defined as any untoward medical occurrence that, at any dose resulted in death, life threatening, required hospitalization, resulted in persistent disability or incapacity, resulted in birth defect, or other situations.
A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
|
Day 1 (after first dose) up to Day 200 (including safety follow up)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC
Time Frame: Day 1 (after first dose) to Day 200
|
Dose-normalized AUC0-inf and body weight-adjusted AUC0-inf for the ravulizumab/rHuPH20 SC cohorts were compared with the 400 mg ravulizumab SC cohort to determine relative bioavailability.
Geometric mean ratios of the AUC0-inf parameter were calculated for each group.
Relative bioavailability is reported as the geometric mean ratio, which was defined as the ratio of the geometric means for the dose-normalized AUC0-inf parameter (with and without body-weight adjustment) for the ravulizumab/rHuPH SC cohort divided by that for the ravulizumab SC cohort.
|
Day 1 (after first dose) to Day 200
|
Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations
Time Frame: Baseline, Up to Day 200
|
The highest (maximum difference) mean (standard deviation [SD]) PCFB at up to Day 200 is reported.
Baseline was defined as the last available value prior to the first drug administration.
Change from Baseline was calculated as observed value minus the baseline value.
PCFB was calculated as change from baseline divided by baseline multiplied by 100.
|
Baseline, Up to Day 200
|
Maximum PCFB In Serum Levels Of Free C5 Concentrations
Time Frame: Baseline, Day 200
|
The highest (maximum difference) mean (SD) PCFB at up to Day 200 is reported.
Baseline was defined as the last available value prior to the first drug administration.
Change from Baseline was calculated as observed value minus the baseline value.
PCFB was calculated as change from baseline divided by baseline multiplied by 100.
|
Baseline, Day 200
|
Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity
Time Frame: Baseline, Up to Day 200
|
The highest (maximum difference) mean (SD) PCFB at up to Day 200 is reported.
Baseline was defined as the last available value prior to the first drug administration.
Change from Baseline was calculated as observed value minus the baseline value.
PCFB was calculated as change from baseline divided by baseline multiplied by 100.
|
Baseline, Up to Day 200
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 9, 2018
Primary Completion (Actual)
May 21, 2019
Study Completion (Actual)
May 21, 2019
Study Registration Dates
First Submitted
May 25, 2022
First Submitted That Met QC Criteria
May 25, 2022
First Posted (Actual)
May 31, 2022
Study Record Updates
Last Update Posted (Actual)
January 22, 2024
Last Update Submitted That Met QC Criteria
April 28, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALXN1210-HV-105
- 2017-004931-35 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy
-
Prevent Age Resort "Pervaya Liniya"RecruitingHealthy Aging | Healthy Diet | Healthy LifestyleRussian Federation
-
Yale UniversityNot yet recruitingHealth-related Benefits of Introducing Table Olives Into the Diet of Young Adults: Olives For HealthHealthy Diet | Healthy Lifestyle | Healthy Nutrition | CholesterolUnited States
-
Maastricht University Medical CenterCompletedHealthy Volunteers | Healthy Subjects | Healthy AdultsNetherlands
-
Hasselt UniversityRecruitingHealthy | Healthy AgingBelgium
-
Galera Therapeutics, Inc.Syneos HealthCompleted
-
Galera Therapeutics, Inc.Syneos HealthCompletedHealthy | Healthy VolunteersAustralia
-
University of PennsylvaniaActive, not recruitingHealthy | Healthy AgingUnited States
-
Chalmers University of TechnologyGöteborg UniversityCompletedHealthy | Nutrition, HealthySweden
-
University of ManitobaNot yet recruitingHealthy | Healthy Diet
Clinical Trials on Ravulizumab
-
Alexion Pharmaceuticals, Inc.CompletedParoxysmal Nocturnal HemoglobinuriaItaly, Spain, Belgium, France, Turkey, Austria, Brazil, Netherlands, Australia, Finland, Russian Federation, Sweden, Canada, United States
-
BioCryst PharmaceuticalsTerminatedBCX9930 for Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy (REDEEM-1)Paroxysmal Nocturnal Hemoglobinuria (PNH)United Kingdom, Hungary, France, Italy, Spain
-
Brigham and Women's HospitalActive, not recruiting
-
Alexion Pharmaceuticals, Inc.CompletedAtypical Hemolytic Uremic Syndrome (aHUS)United States, France, Spain, Taiwan, United Kingdom, Australia, Belgium, Germany, Italy, Japan, Korea, Republic of, Russian Federation, Austria, Canada
-
Alexion Pharmaceuticals, Inc.CompletedHealthyUnited Kingdom
-
Alexion PharmaceuticalsCompletedParoxysmal Nocturnal Hemoglobinuria | PNHKorea, Republic of, Canada, France, Germany, Spain, Taiwan, United Kingdom
-
Alexion Pharmaceuticals, Inc.RecruitingChronic Kidney Disease | CKD | Cardiopulmonary Bypass | Cardiac DiseaseUnited States, China, Germany, Italy, Korea, Republic of, Spain, Japan, Brazil, India, Taiwan, Australia, Israel, Hong Kong, United Kingdom, Poland, Argentina, Canada, Turkey, Netherlands
-
Alexion Pharmaceuticals, Inc.RecruitingParoxysmal Nocturnal HemoglobinuriaItaly
-
AlexionCompletedParoxysmal Nocturnal Hemoglobinuria (PNH)United States, Korea, Republic of, Canada, France, Germany, Spain, United Kingdom, Japan, Australia, Italy, Netherlands
-
Alexion Pharmaceuticals, Inc.CompletedAtypical Hemolytic Uremic Syndrome (aHUS)Italy, United States, Korea, Republic of, Spain, Germany, Belgium, United Kingdom