HealthyPhase 1NCT05396742
Pharmacokinetic Study of Ravulizumab Administered Subcutaneously With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adult Volunteers
A Phase 1 study testing Ravulizumab and rHuPH20 in people with Healthy, run by Alexion Pharmaceuticals, Inc. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Ravulizumab and rHuPH20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Aug 2018to 21 May 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Healthy
- Being tested
- Ravulizumab, rHuPH20
- Keywords
- ALXN1210, Pharmacokinetic, Pharmacodynamic, Safety, Immunogenicity, Ravulizumab, rHuPH20
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RavulizumabDrug
Also called Ultomiris, ALXN1210
Solution for infusion or injection, as applicable
rHuPH20Drug
Also called Recombinant human hyaluronidase PH20
Solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants received a single dose of ravulizumab SC 400 (milligrams) mg . Receives: Drug: Ravulizumab |
| Cohort 2 | Experimental | Participants received a single dose of ravulizumab SC 500 mg/rHuPH20 10000 units. Receives: Drug: Ravulizumab; Drug: rHuPH20 |
| Cohort 3 | Experimental | Participants received a single dose of ravulizumab SC 1000 mg/rHuPH20 20000 units. Receives: Drug: Ravulizumab; Drug: rHuPH20 |
| Cohort 4 | Experimental | Participants received a single dose of ravulizumab SC 2000 mg/rHuPH20 40000 units. Receives: Drug: Ravulizumab; Drug: rHuPH20 |
| Cohort 5 | Experimental | Participants received a single dose of ravulizumab intravenously (IV) 400 mg. Receives: Drug: Ravulizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: Day 1 (after first dose) to Day 200
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.
Measured: Baseline, Up to Day 200
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.
Measured: Baseline, Day 200
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.
Measured: Baseline, Up to Day 200
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start9 Aug 2018
- Primary completion21 May 2019
- Study completion21 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05396742
- Sponsor's protocol ID
- ALXN1210-HV-105
- Other IDs
- 2017-004931-35, 2017
- Status last verified
- Apr 2023
- First submitted
- 25 May 2022
- Last updated
- 22 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05396742
- Acronym / sponsor ID
- ALXN1210-HV-105
- Conditions
- Healthy
- Keywords
- ALXN1210, Pharmacokinetic, Pharmacodynamic, Safety, Immunogenicity, Ravulizumab, rHuPH20
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Aug 2018 (actual)
- Primary completion
- 21 May 2019 (actual)
- Study completion
- 21 May 2019 (actual)
- First posted
- 31 May 2022 (actual)
- Results
- Posted 22 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: RavulizumabParticipants received a single dose of ravulizumab SC 400 (milligrams) mg . |
| Cohort 2 | Experimental | Drug: Ravulizumab, Drug: rHuPH20Participants received a single dose of ravulizumab SC 500 mg/rHuPH20 10000 units. |
| Cohort 3 | Experimental | Drug: Ravulizumab, Drug: rHuPH20Participants received a single dose of ravulizumab SC 1000 mg/rHuPH20 20000 units. |
| Cohort 4 | Experimental | Drug: Ravulizumab, Drug: rHuPH20Participants received a single dose of ravulizumab SC 2000 mg/rHuPH20 40000 units. |
| Cohort 5 | Experimental | Drug: RavulizumabParticipants received a single dose of ravulizumab intravenously (IV) 400 mg. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (25 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RavulizumabAlso: Ultomiris, ALXN1210Solution for infusion or injection, as applicable | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| rHuPH20Also: Recombinant human hyaluronidase PH20Solution for infusion | Drug | Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
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.
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.
4 secondary outcomes
Relative Bioavailability Of Ravulizumab SC/rHuPH20 Compared With Ravulizumab SC
Time frame: 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
Maximum PCFB In Serum Levels Of Free C5 Concentrations
Time frame: Baseline, Day 200
Maximum PCFB In Ex Vivo Chicken Red Blood Cell (cRBC) Hemolysis Activity
Time frame: Baseline, Up to Day 200
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ravulizumab and rHuPH20 in people with Healthy, run by Alexion Pharmaceuticals, Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Bioavailability Of Ravulizumab Subcutaneous (SC)/rHuPH20 (time frame: Day 1 (after first dose) to Day 200). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2024.