Healthy
Conditions
Keywords
ALXN1210, Pharmacokinetic, Pharmacodynamic, Safety, Immunogenicity, Ravulizumab, rHuPH20
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.
Interventions
DRUGRavulizumab
Solution for infusion or injection, as applicable
DRUGrHuPH20
Solution for infusion
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | 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. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | 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. |
| Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 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. |
| Maximum PCFB In Serum Levels Of Free C5 Concentrations | 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. |
| Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
Eligible participants who met all inclusion and no exclusion criteria were assigned unique numbers for enrollment and randomization. Randomization was only used when cohorts were enrolled in parallel.
Pre-assignment details
A total of 108 potential participants were screened (including 5 rescreened and 59 rejects \[screen fail\]). A total of 49 participants were ultimately treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants received a single dose of ravulizumab 400 mg subcutaneously. | 7 |
| Cohort 2 Participants received a single dose of ravulizumab 500 mg/rHuPH20 10000 units subcutaneously. | 12 |
| Cohort 3 Participants received a single dose of ravulizumab 1000 mg/rHuPH20 20000 units subcutaneously. | 12 |
| Cohort 4 Participants received a single dose of ravulizumab 2000 mg/rHuPH20 40000 units subcutaneously. | 12 |
| Cohort 5 Participants received a single dose of ravulizumab 400 mg intravenously. | 6 |
| Total | 49 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total | Cohort 4 | Cohort 5 |
|---|---|---|---|---|---|---|
| Age, Continuous | 29.6 years STANDARD_DEVIATION 7.41 | 27.5 years STANDARD_DEVIATION 5.11 | 28.9 years STANDARD_DEVIATION 6.99 | 28.8 years STANDARD_DEVIATION 6.34 | 29.5 years STANDARD_DEVIATION 7.57 | 28.8 years STANDARD_DEVIATION 4.75 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 7 Participants | 12 Participants | 12 Participants | 49 Participants | 12 Participants | 6 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 12 Participants | 12 Participants | 47 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 9 Participants | 9 Participants | 36 Participants | 11 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 7 Participants | 16 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 5 Participants | 33 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 7 / 7 | 11 / 12 | 12 / 12 | 10 / 12 | 5 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Day 1 (after first dose) to Day 200
Population: The Pharmacokinetics (PK) Population included all participants who had sufficient serum concentration data to enable the calculation of PK parameters of at least area under the serum concentration versus time curve (AUC). For this outcome measure, the Number of Participants Analyzed includes the participants from both the IV group and the respective SC group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Dose-normalized AUC0-inf | 64 Percent bioavailability |
| Cohort 1 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Body weight-adjusted and dose-normalized AUC0-inf | 63 Percent bioavailability |
| Cohort 2 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Body weight-adjusted and dose-normalized AUC0-inf | 69 Percent bioavailability |
| Cohort 2 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Dose-normalized AUC0-inf | 73 Percent bioavailability |
| Cohort 3 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Dose-normalized AUC0-inf | 77 Percent bioavailability |
| Cohort 3 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Body weight-adjusted and dose-normalized AUC0-inf | 70 Percent bioavailability |
| Cohort 4 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Dose-normalized AUC0-inf | 84 Percent bioavailability |
| Cohort 4 | Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 | Body weight-adjusted and dose-normalized AUC0-inf | 81 Percent bioavailability |
Primary
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.
Time frame: Day 1 (after first dose) up to Day 200 (including safety follow up)
Population: The Safety Population included all participants who receive at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 7 Participants |
| Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Cohort 2 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 11 Participants |
| Cohort 2 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Cohort 2 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Cohort 2 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 3 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Cohort 3 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Cohort 3 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 3 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 12 Participants |
| Cohort 4 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 10 Participants |
| Cohort 4 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Cohort 4 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Cohort 4 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 5 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Cohort 5 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 5 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Cohort 5 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
Secondary
Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity
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.
Time frame: Baseline, Up to Day 200
Population: The PD Population included all participants who had sufficient free C5 concentration data that enabled the evaluation of the PD effects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | -58.07 Percent change | Standard Deviation 19.382 |
| Cohort 2 | Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | -77.68 Percent change | Standard Deviation 23.765 |
| Cohort 3 | Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | -80.74 Percent change | Standard Deviation 28.153 |
| Cohort 4 | Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | -99.35 Percent change | Standard Deviation 0.684 |
| Cohort 5 | Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity | -98.52 Percent change | Standard Deviation 1.79 |
Secondary
Maximum PCFB In Serum Levels Of Free C5 Concentrations
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.
Time frame: Baseline, Day 200
Population: The PD Population included all participants who had sufficient free C5 concentration data that enabled the evaluation of the PD effects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Maximum PCFB In Serum Levels Of Free C5 Concentrations | -96.83 Percent Change | Standard Deviation 4.783 |
| Cohort 2 | Maximum PCFB In Serum Levels Of Free C5 Concentrations | -99.48 Percent Change | Standard Deviation 0.349 |
| Cohort 3 | Maximum PCFB In Serum Levels Of Free C5 Concentrations | -99.84 Percent Change | Standard Deviation 0.116 |
| Cohort 4 | Maximum PCFB In Serum Levels Of Free C5 Concentrations | -99.90 Percent Change | Standard Deviation 0 |
| Cohort 5 | Maximum PCFB In Serum Levels Of Free C5 Concentrations | -99.90 Percent Change | Standard Deviation 0 |
Secondary
Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations
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.
Time frame: Baseline, Up to Day 200
Population: The Pharmacodynamics (PD) Population included all participants who had sufficient free C5 concentration data that enabled the evaluation of the PD effects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 92.12 Percent change | Standard Deviation 58.332 |
| Cohort 2 | Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 98.68 Percent change | Standard Deviation 27.659 |
| Cohort 3 | Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 107.46 Percent change | Standard Deviation 45.769 |
| Cohort 4 | Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 133.48 Percent change | Standard Deviation 35.782 |
| Cohort 5 | Maximum Percent Change From Baseline (PCFB) In Serum Levels Of Total Complement Component 5 (C5) Concentrations | 112.90 Percent change | Standard Deviation 27.878 |
Secondary
Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC
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.
Time frame: Day 1 (after first dose) to Day 200
Population: The PK Population included all participants who had sufficient serum concentration data to enable the calculation of PK parameters of at least AUC. For this outcome measure, the Number of Participants Analyzed includes the participants from both the ravulizumab/rHuPH SC cohort and the respective ravulizumab SC cohort.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Dose-normalized AUC0-inf | 115 Percent bioavailability |
| Cohort 1 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Body weight-adjusted and dose-normalized AUC0-inf | 109 Percent bioavailability |
| Cohort 2 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Dose-normalized AUC0-inf | 120 Percent bioavailability |
| Cohort 2 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Body weight-adjusted and dose-normalized AUC0-inf | 112 Percent bioavailability |
| Cohort 3 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Dose-normalized AUC0-inf | 132 Percent bioavailability |
| Cohort 3 | Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC | Body weight-adjusted and dose-normalized AUC0-inf | 129 Percent bioavailability |