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

NCT05396742 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ALXN1210-HV-1052017-004931-35
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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

Keywords

ALXN1210; Pharmacokinetic; Pharmacodynamic; Safety; Immunogenicity; Ravulizumab; rHuPH20

Outcome Measures

Primary Outcomes (2)

• Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20

  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)

  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 Outcomes (4)

• Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC

  Day 1 (after first dose) to Day 200

• Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations

  Baseline, Up to Day 200

• Maximum PCFB In Serum Levels Of Free C5 Concentrations

  Baseline, Day 200

• Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity

  Baseline, Up to Day 200

Study Arms (5)

Cohort 1

EXPERIMENTAL

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

Drug: Ravulizumab

Cohort 2

EXPERIMENTAL

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

Drug: Ravulizumab; Drug: rHuPH20

Cohort 3

EXPERIMENTAL

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

Drug: Ravulizumab; Drug: rHuPH20

Cohort 4

EXPERIMENTAL

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

Drug: Ravulizumab; Drug: rHuPH20

Cohort 5

EXPERIMENTAL

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

Drug: Ravulizumab

Interventions

Ravulizumab DRUG

Solution for infusion or injection, as applicable

Also known as: Ultomiris, ALXN1210

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

rHuPH20 DRUG

Solution for infusion

Also known as: Recombinant human hyaluronidase PH20

Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Trial Site

London, United Kingdom

Location

MeSH Terms

Interventions

ravulizumab

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

+1.855.752.2356

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: May 31, 2022
• Study Start: August 9, 2018
• Primary Completion: May 21, 2019
• Study Completion: May 21, 2019
• Last Updated: January 22, 2024
• Results First Posted: January 22, 2024

Record last verified: 2023-04

Locations

GB (1)