Healthy
Conditions
Keywords
ALXN1830, Autoimmune Disease, Pharmacokinetics, Pharmacodynamics
Brief summary
This trial will study the effects of single and multiple doses of ALXN1830 in healthy adult participants.
Detailed description
This is a Phase 1 study in healthy adult participants. The study will consist of 2 single ascending dose (Cohorts 1 and 2) and 4 multiple ascending dose cohorts (Cohorts 3 to 6). Participants will be randomly assigned to each of the 6 cohorts to receive either single or multiple doses of ALXN1830 subcutaneous (SC) or single or multiple doses of placebo SC. Cohort 6 will enroll only healthy participants of Japanese descent who will be dosed according to the highest tolerated dose (HTD) established in the non-Japanese cohorts.
Interventions
DRUGALXN1830
ALXN1830 will be administered as SC infusion(s).
DRUGPlacebo
Placebo will be administered as SC infusion(s).
Sponsors
Syneos Health
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 55 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 60 to 90 kilograms (kg), inclusive, and body mass index within 18 to 30 kg/meter squared, inclusive. * Must be willing to follow protocol-specified contraception guidance during the study and for 3 months after last dose of study drug.
Exclusion criteria
* Current/recurrent diseases or relevant medical history. * Known exposure to investigational or marketed therapeutic proteins, such as monoclonal antibodies, fusion proteins, bispecific molecules, or antibody drug conjugates, within 60 days or 5 half-lives (whichever is longer) prior to dosing. * Participants who have prior exposure to ALXN1830. * Current enrollment or past participation within the last 90 days before signing of consent in this or any other interventional clinical study. * Participants with hepatitis B or C, or human immunodeficiency virus. * 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) | Day 1 (postdose) through follow-up (up to approximately 141 days) | An AE was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE with a start date or time on or after the first dose of the study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 1 | Day 1 (predose up to 12 hours postdose) | Serum total drug concentrations were measured using a validated LC/MS assay. |
| Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 22 | Day 22 (predose up to 12 hours postdose) | Serum total drug concentrations were measured using a validated LC/MS assay. |
| Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 78 | Day 78 (predose up to 12 hours postdose) | Serum total drug concentrations were measured using a validated LC/MS assay. |
| Single-Dose Cohorts: Area Under the Serum Concentration-time Curve From Time 0 (Dosing) To Time Infinity (AUC0-inf) of ALXN1830 | Day 1 (predose) up to Day 64 (postdose) | Serum total drug concentrations were measured using a validated liquid chromatography/mass spectrometry (LC/MS) assay. |
| Percent FcRN Receptor Occupancy at Day 120 | Day 120 | — |
| Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | Day 1 (postdose) through follow-up (up to approximately 141 days) | — |
| Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | Baseline, early termination visit (up to Day 141) | Serum concentration of IgG was measured using validated nephelometric assays. |
Countries
New Zealand
Participant flow
Pre-assignment details
A total of 34 participants (25 ALXN1830 treated and 9 placebo-treated) were enrolled and randomized in a 6:2 ratio in 5 cohorts. Healthy, Japanese participants were planned to be dosed in Cohort 6 according to the highest tolerated dose (HTD) established in the non-Japanese cohorts. This cohort was not achieved due to early termination of the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ALXN1830 Single Medium Dose Participants received a single SC medium dose of ALXN1830. | 6 |
| Cohort 2: ALXN1830 Single High Dose Participants received a single SC high dose of ALXN1830. | 1 |
| Cohort 3: ALXN1830 Multiple Low Dose Participants received multiple SC low doses of ALXN1830 QW. | 6 |
| Cohort 4: ALXN1830 Multiple Medium Dose Participants received multiple SC medium doses of ALXN1830 QW. | 6 |
| Cohort 5: ALXN1830 Multiple High Dose Participants received multiple SC high doses of ALXN1830 QW. | 6 |
| Placebo Participants received placebo matched to ALXN1830. | 9 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Cohort 1: ALXN1830 Single Medium Dose | Cohort 5: ALXN1830 Multiple High Dose | Cohort 4: ALXN1830 Multiple Medium Dose | Cohort 3: ALXN1830 Multiple Low Dose | Cohort 2: ALXN1830 Single High Dose |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 34 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Another Hispanic, Latino/a, or Spanish origin | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not of Hispanic, Latino/a, or Spanish origin | 5 Participants | 23 Participants | 4 Participants | 6 Participants | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 1 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian Indian | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Chinese | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 8 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Samoan | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 4 Participants | 19 Participants | 5 Participants | 3 Participants | 3 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 17 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 17 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 0 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 6 / 6 | 1 / 1 | 6 / 6 | 6 / 6 | 5 / 6 | 7 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE with a start date or time on or after the first dose of the study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Day 1 (postdose) through follow-up (up to approximately 141 days)
Population: The Safety Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: ALXN1830 Single Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Cohort 2: ALXN1830 Single High Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Cohort 3: ALXN1830 Multiple Low Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Cohort 4: ALXN1830 Multiple Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Cohort 5: ALXN1830 Multiple High Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 7 Participants |
Secondary
Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141)
Serum concentration of IgG was measured using validated nephelometric assays.
Time frame: Baseline, early termination visit (up to Day 141)
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug (active and placebo) who had evaluable serum Immunoglobulin data (IgG, IgG subtypes, Ig subtypes, and circulating immune complexes \[CIC\]) or neonatal crystallizable fragment receptor (FcRn) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1830 Single Medium Dose | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | -0.60 grams (g)/L | Standard Deviation 1.037 |
| Cohort 2: ALXN1830 Single High Dose | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | -1.00 grams (g)/L | — |
| Cohort 3: ALXN1830 Multiple Low Dose | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | -0.22 grams (g)/L | Standard Deviation 1.504 |
| Cohort 4: ALXN1830 Multiple Medium Dose | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | -0.70 grams (g)/L | Standard Deviation 0.899 |
| Cohort 5: ALXN1830 Multiple High Dose | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | 0.10 grams (g)/L | Standard Deviation 0.555 |
| Placebo | Change From Baseline in Serum Immunoglobulin G (IgG) at Early Termination Visit (up to Day 141) | -0.17 grams (g)/L | Standard Deviation 1.122 |
Secondary
Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 1
Serum total drug concentrations were measured using a validated LC/MS assay.
Time frame: Day 1 (predose up to 12 hours postdose)
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug (only active) and had at least 1 postdose serum ALXN1830 concentration measured. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Per prespecified analysis, only participants in Cohort 5 were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3: ALXN1830 Multiple Low Dose | Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 1 | 340.085 hours*mg/L | Standard Deviation 162.0531 |
Secondary
Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 22
Serum total drug concentrations were measured using a validated LC/MS assay.
Time frame: Day 22 (predose up to 12 hours postdose)
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug (only active) and had at least 1 postdose serum ALXN1830 concentration measured. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Per prespecified analysis, only participants in Cohort 4 were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: ALXN1830 Single High Dose | Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 22 | 333.787 hours*mg/L | Standard Deviation 143.739 |
Secondary
Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 78
Serum total drug concentrations were measured using a validated LC/MS assay.
Time frame: Day 78 (predose up to 12 hours postdose)
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug (only active) and had at least 1 postdose serum ALXN1830 concentration measured. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint. Per prespecified analysis, only participants in Cohort 3 were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: ALXN1830 Single Medium Dose | Multiple-Dose Cohorts: AUC0-inf of ALXN1830 at Day 78 | 847.380 hours*mg/L |
Secondary
Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830
Time frame: Day 1 (postdose) through follow-up (up to approximately 141 days)
Population: The Immunogenicity Set included all participants who had a predose (baseline) and at least 1 postdose ADA sample collected.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: ALXN1830 Single Medium Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 4 Participants |
| Cohort 1: ALXN1830 Single Medium Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 6 Participants |
| Cohort 2: ALXN1830 Single High Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 0 Participants |
| Cohort 2: ALXN1830 Single High Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 1 Participants |
| Cohort 3: ALXN1830 Multiple Low Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 6 Participants |
| Cohort 3: ALXN1830 Multiple Low Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 6 Participants |
| Cohort 4: ALXN1830 Multiple Medium Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 4 Participants |
| Cohort 4: ALXN1830 Multiple Medium Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 6 Participants |
| Cohort 5: ALXN1830 Multiple High Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 5 Participants |
| Cohort 5: ALXN1830 Multiple High Dose | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 2 Participants |
| Placebo | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | ADA positive | 6 Participants |
| Placebo | Number of Participants With Antidrug Antibodies (ADA) and Neutralizing Antibodies (NAb) to ALXN1830 | NAb | 2 Participants |
Secondary
Percent FcRN Receptor Occupancy at Day 120
Time frame: Day 120
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug (active and placebo) who had evaluable serum Immunoglobulin data (IgG, IgG subtypes, Ig subtypes, and CIC) or FcRn data. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3: ALXN1830 Multiple Low Dose | Percent FcRN Receptor Occupancy at Day 120 | 12.07 percentage of receptor occupied | Geometric Coefficient of Variation 92 |
| Placebo | Percent FcRN Receptor Occupancy at Day 120 | 6.40 percentage of receptor occupied | — |
Secondary
Single-Dose Cohorts: Area Under the Serum Concentration-time Curve From Time 0 (Dosing) To Time Infinity (AUC0-inf) of ALXN1830
Serum total drug concentrations were measured using a validated liquid chromatography/mass spectrometry (LC/MS) assay.
Time frame: Day 1 (predose) up to Day 64 (postdose)
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug (only active) and had at least 1 postdose serum ALXN1830 concentration measured. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: ALXN1830 Single Medium Dose | Single-Dose Cohorts: Area Under the Serum Concentration-time Curve From Time 0 (Dosing) To Time Infinity (AUC0-inf) of ALXN1830 | 360.940 hours*milligram (mg)/liter (L) |
| Cohort 2: ALXN1830 Single High Dose | Single-Dose Cohorts: Area Under the Serum Concentration-time Curve From Time 0 (Dosing) To Time Infinity (AUC0-inf) of ALXN1830 | 291.930 hours*milligram (mg)/liter (L) |