Healthy
Conditions
Brief summary
This study will evaluate the effects of single ascending doses (SAD) and multiple ascending doses (MAD) of ALXN1830 administered subcutaneously (SC) to healthy adult participants.
Detailed description
This Phase 1 study will consist of 3 SAD (Cohorts 1 to 3) and 4 MAD (Cohorts 4 to 7) cohorts. Participants will be randomly assigned in a 6:2 ratio to each of the 7 cohorts to receive either single or multiple doses of ALXN1830 (n = 6 per cohort) or single or multiple doses of placebo (n = 2 per cohort).
Interventions
DRUGALXN1830
ALXN1830 will be administered as SC infusion(s).
DRUGPlacebo
Placebo will be administered as SC infusion(s).
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Satisfactory medical assessment. * Participants must have had vaccination against pneumococcus (Pneumovax 23 \[PPSV23\]) at least 28 days, and maximally 4 years prior to Day 1. * Participants must have had seasonal influenza vaccination for the current season at least 28 days prior to Day 1. * Body weight within 50 to 90 kg, inclusive, and body mass index (BMI) within the range of 18 to 24.9 kg/m\^2, inclusive. * Must be willing to follow protocol-specified contraception guidance during the study and for up to 3 months after last dose of study drug.
Exclusion criteria
* Current/recurrent diseases or relevant medical history. * Known exposure to therapeutic proteins, such as monoclonal antibodies, including marketed drugs prior to dosing. * Participants who have prior exposure to ALXN1830. * Exposure to more than 4 new (small molecule) investigational compounds within 12 months prior to dosing. * Current enrollment or past participation within the last 90 days before signing of consent in this or any other interventional clinical study. * Presence of hepatitis B surface antigen (HBsAg) at Screening. * Positive hepatitis C antibody test result at Screening. * Positive human immunodeficiency virus (HIV) antibody test at Screening. * Participants who are either immunocompromised or have one of the following underlying medical conditions: anatomic or functional asplenia (including sickle cell disease); primary antibody deficiencies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to Day 64 | A TEAE was defined as any adverse event (AE) that commences after the start of administration of study drug. An AE is 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. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. A summary of all serious AEs and other AEs (nonserious) regardless of causality is located in 'Adverse events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To The Last Quantifiable Concentration (AUC0-t) of ALXN1830 | Predose, end of infusion, and 0.5, 2, 4, 8, and 12 hours postdose on Day 1; and Days 2 to 8 | — |
| Percent Change From Baseline in Immunoglobulin G (IgG) Levels at Day 10 | Baseline, Day 10 | — |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | Baseline up to Day 64 | — |
| Number of Participants With Positive Neutralizing Antibodies (NAbs) | Baseline up to Day 64 | All samples that are confirmed positive for ADA were evaluated for the presence of neutralizing antibodies. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Due to a lack of participant availability caused by the COVID-19 pandemic, the study was terminated on 22 January 2021 after completion of the ALXN1830 subcutaneous 750 milligrams (mg) dose or placebo groups and partial enrollment of the ALXN1830 subcutaneous 1250 mg dose or placebo groups.
Participants by arm
| Arm | Count |
|---|---|
| ALXN1830 750 mg Participants received a single dose of ALXN1830 750 mg subcutaneously on Day 1. | 6 |
| ALXN1830 1250 mg Participants received a single dose of ALXN1830 1250 mg subcutaneously on Day 1. | 3 |
| Placebo Participants received placebo matched to ALXN1830 subcutaneously on Day 1. | 3 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ALXN1830 750 mg | ALXN1830 1250 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 22.8 years STANDARD_DEVIATION 2.93 | 23.0 years STANDARD_DEVIATION 3.46 | 28.3 years STANDARD_DEVIATION 5.86 | 24.3 years STANDARD_DEVIATION 4.29 |
| Race/Ethnicity, Customized Race Chinese | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Another Hispanic, Latino/a, or Spanish Origin | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not of Hispanic, Latino/a, or Spanish Origin | 6 Participants | 3 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 5 / 6 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE was defined as any adverse event (AE) that commences after the start of administration of study drug. An AE is 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. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. A summary of all serious AEs and other AEs (nonserious) regardless of causality is located in 'Adverse events' Section.
Time frame: Baseline up to Day 64
Population: The safety population consisted of all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALXN1830 750 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AEs | 5 Participants |
| ALXN1830 750 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| ALXN1830 1250 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AEs | 3 Participants |
| ALXN1830 1250 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AEs | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
Secondary
Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To The Last Quantifiable Concentration (AUC0-t) of ALXN1830
Time frame: Predose, end of infusion, and 0.5, 2, 4, 8, and 12 hours postdose on Day 1; and Days 2 to 8
Population: The pharmacokinetic (PK) population consisted of all participants who had sufficient serum ALXN1830 concentration data to evaluate PK parameters. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1830 750 mg | Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To The Last Quantifiable Concentration (AUC0-t) of ALXN1830 | 31.8 hour*nanogram/milliliter | — |
| ALXN1830 1250 mg | Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To The Last Quantifiable Concentration (AUC0-t) of ALXN1830 | 44.2 hour*nanogram/milliliter | Standard Deviation 33.7 |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Time frame: Baseline up to Day 64
Population: The immunogenicity population consisted of all participants who had ADA sample collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1830 750 mg | Number of Participants With Positive Anti-Drug Antibodies (ADA) | 4 Participants |
| ALXN1830 1250 mg | Number of Participants With Positive Anti-Drug Antibodies (ADA) | 2 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) | 0 Participants |
Secondary
Number of Participants With Positive Neutralizing Antibodies (NAbs)
All samples that are confirmed positive for ADA were evaluated for the presence of neutralizing antibodies.
Time frame: Baseline up to Day 64
Population: The immunogenicity population consisted of all participants who had ADA sample collected. Here, 'Overall number of participants analyzed' = participants with positive ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1830 750 mg | Number of Participants With Positive Neutralizing Antibodies (NAbs) | 2 Participants |
| ALXN1830 1250 mg | Number of Participants With Positive Neutralizing Antibodies (NAbs) | 2 Participants |
Secondary
Percent Change From Baseline in Immunoglobulin G (IgG) Levels at Day 10
Time frame: Baseline, Day 10
Population: The pharmacodynamic (PD) population consisted of all participants who had sufficient serum IgG data to evaluate pharmacodynamics effects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1830 750 mg | Percent Change From Baseline in Immunoglobulin G (IgG) Levels at Day 10 | -36.137 percent change | Standard Deviation 3.7163 |
| ALXN1830 1250 mg | Percent Change From Baseline in Immunoglobulin G (IgG) Levels at Day 10 | -39.044 percent change | Standard Deviation 2.0933 |
| Placebo | Percent Change From Baseline in Immunoglobulin G (IgG) Levels at Day 10 | -2.369 percent change | Standard Deviation 6.6831 |