Healthy
Conditions
Keywords
ALXN1820, Properdin, Pharmacodynamics, Pharmacokinetics
Brief summary
This is a Phase 1, randomized, double-blind, placebo-controlled single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN1820 administered subcutaneously (SC) (ALXN1820 SC) and intravenously (IV) (ALXN1820 IV).
Detailed description
This study will include up to 10 different dosing cohorts, with each cohort consisting of 2 groups (ALXN1820 group, placebo group). Participants will be randomly assigned in a 3:1 ratio to each of these 2 groups, respectively, within all 10 cohorts, to receive either a single or multiple doses of ALXN1820 SC, a single dose of ALXN1820 IV, or a single or multiple doses of placebo. The study will be conducted in healthy adult participants and will also include a multiple SC dose cohort in healthy participants of Japanese descent.
Interventions
DRUGALXN1820 IV
ALXN1820 IV (450 mg) will be administered as an IV infusion.
DRUGALXN1820 SC
ALXN1820 SC will be administered as a manual SC push or SC infusion via a syringe pump. Doses will range from 12.5 milligrams (mg) to a maximum of 2250 mg. Multiple dosing duration will range from 3 to 5 weeks.
DRUGPlacebo SC
Placebo SC will be administered as a manual SC push or SC infusion via a syringe pump.
DRUGPlacebo IV
Placebo IV will be administered as an IV infusion.
Sponsors
Syneos Health
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Body weight 50 to 100 kilograms (kg); body mass index 17 to 32 kg/meter squared. * Cohort 9 only: Japanese participants (defined as those participants whose parents and grandparents are both Japanese and who have spent less than 5 years outside of Japan). * Satisfactory medical assessment. * Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose. * Vaccination requirement: * Vaccination with tetravalent meningococcal conjugate vaccine at least 56 days and not more than 2 years, 6 months prior to dosing; * Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing, with a booster at least 28 days prior to dosing, with at least 28 days between the first and second injections.
Exclusion criteria
* Current/recurrent diseases or relevant medical history. * History of any Neisseria infection. * Hepatitis B/C, human immunodeficiency virus. * History of latent or active tuberculosis (TB), or positive TB test. * Active systemic infection within 14 days of dosing. * Risk of meningococcal infections due to living/working conditions. * History of complement deficiency or complement activity below the reference range. * Participation in a clinical study within 90 days or 5 half lives of the investigational agent (whichever is longer) before initiation of dosing on Day 1. * Participation in more than 1 clinical study of a monoclonal antibody (mAb), or participation in a clinical study of a mAb within the 6 months or 5 half lives of the mAb (whichever is longer) prior to screening. * Acquired complement deficiencies (for example, those receiving eculizumab).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155 | An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as any AEs that commenced after the start of administration of study intervention. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported AEs' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts | Up to 154 days following the first day of dosing | — |
| Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | Up to 126 days following the first day of dosing | — |
| Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts | Up to 154 days following the first day of dosing | — |
| Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | Baseline, Day 127 | — |
| Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | Baseline, Day 127 | — |
| Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | Up to 126 days following the first day of dosing | — |
| Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts | Baseline, Day 155 | — |
| Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | Baseline, Day 127 | — |
| Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts | Baseline, Day 155 | — |
| Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | Baseline up to Day 155 | — |
| Absolute Bioavailability Of ALXN1820 SC | Baseline up to Day 127 | The absolute bioavailability was expressed as ratio and was calculated as the geometric mean for the AUC\[0-inf\] for SC divided by the geometric mean for the AUC\[0-inf\] for IV. Least square means were calculated with cohort, treatment, and sequence as the fixed effects, and participant-participant (sequence) as a random effect. |
| Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts | Baseline, Day 155 | — |
Countries
Australia, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ALXN1820 12.5 mg SC Healthy participants received a single dose of ALXN1820 12.5 mg SC injection on Day 1. | 5 |
| Cohort 2: ALXN1820 50 mg SC Healthy participants received a single dose of ALXN1820 50 mg SC injection on Day 1. | 6 |
| Cohort 3: ALXN1820 150 mg SC Healthy participants received a single dose of ALXN1820 150 mg SC injection on Day 1. | 5 |
| Cohort 4: ALXN1820 450 mg SC Healthy participants received a single dose of ALXN1820 450 mg SC injection on Day 1. | 5 |
| Cohort 5: ALXN1820 450 mg IV Healthy participants received a single dose of ALXN1820 450 mg IV infusion on Day 1. | 5 |
| Cohort 6: ALXN1820 1200 mg SC Healthy participants received a single dose of ALXN1820 1200 mg SC injection on Day 1. | 6 |
| Cohort 8: ALXN1820 150 mg SC (QW*5) Healthy participants received multiple doses of ALXN1820 150 mg SC injection once weekly for 5 weeks. | 7 |
| Cohort 9: ALXN1820 150 mg SC (QW*5) Healthy Japanese participants received multiple doses of ALXN1820 150 mg SC injection once weekly for 5 weeks. | 6 |
| All Placebo Healthy participants received placebo matched to ALXN1820 SC injection or IV infusion. | 15 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 2: ALXN1820 50 mg SC | Cohort 3: ALXN1820 150 mg SC | Cohort 1: ALXN1820 12.5 mg SC | Cohort 4: ALXN1820 450 mg SC | Cohort 5: ALXN1820 450 mg IV | Cohort 6: ALXN1820 1200 mg SC | Cohort 8: ALXN1820 150 mg SC (QW*5) | Cohort 9: ALXN1820 150 mg SC (QW*5) | All Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 6 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 7 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 4 Participants | 5 Participants | 5 Participants | 4 Participants | 3 Participants | 6 Participants | 7 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 5 Participants | 7 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Female | 32 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Male | 28 Participants | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 6 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 15 |
| other Total, other adverse events | 4 / 5 | 6 / 6 | 2 / 5 | 4 / 5 | 4 / 5 | 6 / 6 | 6 / 7 | 5 / 6 | 11 / 15 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 15 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV
An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as any AEs that commenced after the start of administration of study intervention. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported AEs' Section.
Time frame: Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155
Population: The Safety Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 1 Participants |
| Cohort 2: ALXN1820 50 mg SC | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 3: ALXN1820 150 mg SC | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 4: ALXN1820 450 mg SC | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 4 Participants |
| Cohort 5: ALXN1820 450 mg IV | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 2 Participants |
| Cohort 6: ALXN1820 1200 mg SC | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 8: ALXN1820 150 mg SC (QW*5) | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 1 Participants |
| Cohort 9: ALXN1820 150 mg SC (QW*5) | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 3 Participants |
| All Placebo | Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV | 2 Participants |
Secondary
Absolute Bioavailability Of ALXN1820 SC
The absolute bioavailability was expressed as ratio and was calculated as the geometric mean for the AUC\[0-inf\] for SC divided by the geometric mean for the AUC\[0-inf\] for IV. Least square means were calculated with cohort, treatment, and sequence as the fixed effects, and participant-participant (sequence) as a random effect.
Time frame: Baseline up to Day 127
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and had at least 1 post-dose PK concentration measured. Data for the arms reported is from the data collected based on pre-specified analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Absolute Bioavailability Of ALXN1820 SC | 89.307 Ratio |
Secondary
Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts
Time frame: Up to 126 days following the first day of dosing
Population: The Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 post-dose PK concentration measured. As per pre-specified analysis, only data for Cohorts 1-6 were collected for this Outcome Measure. Here, number analyzed (n) signifies those participants who were evaluable at specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 1708.745740 hours*micrograms/milliliters | — |
| Cohort 1: ALXN1820 12.5 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 1301.090561 hours*micrograms/milliliters | Geometric Coefficient of Variation 35.33 |
| Cohort 2: ALXN1820 50 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 11871.887397 hours*micrograms/milliliters | Geometric Coefficient of Variation 18.11 |
| Cohort 2: ALXN1820 50 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 11356.654811 hours*micrograms/milliliters | Geometric Coefficient of Variation 18.25 |
| Cohort 3: ALXN1820 150 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 22447.444516 hours*micrograms/milliliters | Geometric Coefficient of Variation 24.22 |
| Cohort 3: ALXN1820 150 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 21767.138401 hours*micrograms/milliliters | Geometric Coefficient of Variation 24.61 |
| Cohort 4: ALXN1820 450 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 65994.232565 hours*micrograms/milliliters | Geometric Coefficient of Variation 23.56 |
| Cohort 4: ALXN1820 450 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 56467.567738 hours*micrograms/milliliters | Geometric Coefficient of Variation 37.45 |
| Cohort 5: ALXN1820 450 mg IV | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 69126.480691 hours*micrograms/milliliters | Geometric Coefficient of Variation 13.16 |
| Cohort 5: ALXN1820 450 mg IV | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 70222.568018 hours*micrograms/milliliters | Geometric Coefficient of Variation 13.41 |
| Cohort 6: ALXN1820 1200 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUCtau | 151825.555391 hours*micrograms/milliliters | Geometric Coefficient of Variation 15.02 |
| Cohort 6: ALXN1820 1200 mg SC | Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts | AUC0-inf | 157445.098602 hours*micrograms/milliliters | Geometric Coefficient of Variation 15.8 |
Secondary
Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts
Time frame: Up to 154 days following the first day of dosing
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and had at least 1 post-dose PK concentration measured. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 8 and 9 were collected for this Outcome Measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts | 13047.247486 hours*micrograms/milliliters | Geometric Coefficient of Variation 11.96 |
| Cohort 2: ALXN1820 50 mg SC | Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts | 14895.697459 hours*micrograms/milliliters | Geometric Coefficient of Variation 6.63 |
Secondary
Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts
Time frame: Baseline, Day 155
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 8 and 9 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts | 27.9714 percentage of activity | Standard Deviation 34.63436 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts | 2.6667 percentage of activity | Standard Deviation 25.0242 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts | 7.0000 percentage of activity | Standard Deviation 15.05169 |
Secondary
Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts
Time frame: Baseline, Day 127
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 1-6 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | -15.6800 percentage of activity | Standard Deviation 19.0677 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 5.0833 percentage of activity | Standard Deviation 28.14281 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1.6600 percentage of activity | Standard Deviation 18.75241 |
| Cohort 4: ALXN1820 450 mg SC | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 10.3750 percentage of activity | Standard Deviation 35.92282 |
| Cohort 5: ALXN1820 450 mg IV | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 3.100 percentage of activity | Standard Deviation 23.43683 |
| Cohort 6: ALXN1820 1200 mg SC | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 6.6500 percentage of activity | Standard Deviation 20.32956 |
| Cohort 8: ALXN1820 150 mg SC (QW*5) | Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 5.8091 percentage of activity | Standard Deviation 25.66349 |
Secondary
Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts
Time frame: Baseline, Day 127
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 1-6 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 848.0 nanograms/milliliters | Standard Deviation 508.4 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1096.7 nanograms/milliliters | Standard Deviation 1815.02 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1200.0 nanograms/milliliters | Standard Deviation 1078.61 |
| Cohort 4: ALXN1820 450 mg SC | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 20.8 nanograms/milliliters | Standard Deviation 2667.17 |
| Cohort 5: ALXN1820 450 mg IV | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1188.4 nanograms/milliliters | Standard Deviation 975.93 |
| Cohort 6: ALXN1820 1200 mg SC | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 5171.8 nanograms/milliliters | Standard Deviation 910.95 |
| Cohort 8: ALXN1820 150 mg SC (QW*5) | Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | -26.6 nanograms/milliliters | Standard Deviation 1749.15 |
Secondary
Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts
Time frame: Baseline, Day 155
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 8 and 9 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts | 3775.2 nanograms/milliliters | Standard Deviation 1480.18 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts | 3762.0 nanograms/milliliters | Standard Deviation 796.41 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts | 154.5 nanograms/milliliters | Standard Deviation 480.34 |
Secondary
Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts
Time frame: Baseline, Day 127
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 1-6 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 3.744 micrograms/milliliters | Standard Deviation 0.8941 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 2.093 micrograms/milliliters | Standard Deviation 1.387 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1.788 micrograms/milliliters | Standard Deviation 1.7589 |
| Cohort 4: ALXN1820 450 mg SC | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 5.580 micrograms/milliliters | Standard Deviation 3.1652 |
| Cohort 5: ALXN1820 450 mg IV | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 3.014 micrograms/milliliters | Standard Deviation 2.0181 |
| Cohort 6: ALXN1820 1200 mg SC | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 15.017 micrograms/milliliters | Standard Deviation 7.1687 |
| Cohort 8: ALXN1820 150 mg SC (QW*5) | Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts | 1.240 micrograms/milliliters | Standard Deviation 1.4712 |
Secondary
Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts
Time frame: Baseline, Day 155
Population: The Pharmacodynamic Set included all participants who received at least 1 dose of study drug and had evaluable properdin concentration, CAP or complement classical pathway activity data. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 8 and 9 and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts | 6.018 micrograms/milliliters | Standard Deviation 2.5094 |
| Cohort 2: ALXN1820 50 mg SC | Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts | 9.878 micrograms/milliliters | Standard Deviation 1.6731 |
| Cohort 3: ALXN1820 150 mg SC | Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts | 0.418 micrograms/milliliters | Standard Deviation 0.2806 |
Secondary
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts
Time frame: Up to 154 days following the first day of dosing
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and had at least 1 post-dose PK concentration measured. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure. As per pre-specified analysis, only data for Cohorts 8 and 9 were collected for this Outcome Measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts | 90.53 micrograms/milliliters | Geometric Coefficient of Variation 12.4 |
| Cohort 2: ALXN1820 50 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts | 100.97 micrograms/milliliters | Geometric Coefficient of Variation 7.94 |
Secondary
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts
Time frame: Up to 126 days following the first day of dosing
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and had at least 1 post-dose PK concentration measured. As per pre-specified analysis, only data for Cohorts 1-6 were collected for this Outcome Measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 2.346 micrograms/milliliters | Geometric Coefficient of Variation 17.85 |
| Cohort 2: ALXN1820 50 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 12.892 micrograms/milliliters | Geometric Coefficient of Variation 10.48 |
| Cohort 3: ALXN1820 150 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 29.342 micrograms/milliliters | Geometric Coefficient of Variation 22.53 |
| Cohort 4: ALXN1820 450 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 99.256 micrograms/milliliters | Geometric Coefficient of Variation 33.98 |
| Cohort 5: ALXN1820 450 mg IV | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 162.518 micrograms/milliliters | Geometric Coefficient of Variation 46.73 |
| Cohort 6: ALXN1820 1200 mg SC | Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts | 246.140 micrograms/milliliters | Geometric Coefficient of Variation 17.14 |
Secondary
Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV
Time frame: Baseline up to Day 155
Population: The Immunogenicity Set included all participants who had a predose and at least 1 postdose ADA sample collected. As per pre-specified analysis, only data for Cohorts 1-6, and Cohorts 8 and 9, and the placebo arm were collected for this Outcome Measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: ALXN1820 12.5 mg SC | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 2: ALXN1820 50 mg SC | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 3: ALXN1820 150 mg SC | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 4: ALXN1820 450 mg SC | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 5: ALXN1820 450 mg IV | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 6: ALXN1820 1200 mg SC | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |
| Cohort 8: ALXN1820 150 mg SC (QW*5) | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 2 Participants |
| Cohort 9: ALXN1820 150 mg SC (QW*5) | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 1 Participants |
| All Placebo | Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV | 0 Participants |