Hypophosphatasia
Conditions
Keywords
HPP, enzyme replacement therapy, low alkaline phosphatase, tissue-nonspecific alkaline phosphatase, TNSALP
Brief summary
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.
Interventions
BIOLOGICALALXN1850
ALXN1850 will be administered as an IV infusion and via the SC route.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Study participants will be enrolled into 3 cohorts in a sequential fashion.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed clinical diagnosis of HPP * Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion * Willing and able to follow protocol-specified contraception requirements * Willing and able to give informed consent
Exclusion criteria
* Primary or secondary hyperparathyroidism or hypoparathyroidism * Fracture within 12 weeks of screening * Current or relevant history of unstable physical or psychiatric illness * Significant allergies * Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 up to Day 85 | TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. 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 |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850 | Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29 |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29 |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850 | Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29 |
| Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
| Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
| Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29 |
| Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
| Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
| Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
| Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | Baseline up to Day 85 |
| Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants received 15 mg of ALXN1850 as a single intravenous dose, followed by 15 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses. | 5 |
| Cohort 2 Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses. | 5 |
| Cohort 3 Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 3 | Cohort 1 | Total |
|---|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 12.52 | 54.6 years STANDARD_DEVIATION 9.07 | 44.2 years STANDARD_DEVIATION 12.44 | 45.5 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 3 / 5 | 5 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 1 / 5 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. 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 up to Day 85
Population: The Safety Set included all participants who received any amount of study drug. Participants were analyzed according to the study drug received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
Secondary
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Number analyzed signifies those participants who were evaluable for the prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | 1 Week post Day 1 IV Dose | -1.620 micromoles (uM) | — |
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | 1 Week post Day 29 SC Dose 3 | -0.813 micromoles (uM) | Standard Deviation 0.597 |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | 1 Week post Day 1 IV Dose | -1.930 micromoles (uM) | — |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | 1 Week post Day 29 SC Dose 3 | -1.505 micromoles (uM) | Standard Deviation 0.1202 |
| Cohort 3 | Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1 | 1 Week post Day 29 SC Dose 3 | -2.040 micromoles (uM) | — |
Secondary
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The Pharmacodynamic (PD) Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 1 IV Dose | -18.300 nanogram/milliliter | — |
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 29 SC Dose 3 | -97.950 nanogram/milliliter | Standard Deviation 164.0193 |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 1 IV Dose | -7.600 nanogram/milliliter | — |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 29 SC Dose 3 | -38.573 nanogram/milliliter | Standard Deviation 26.4932 |
| Cohort 3 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 1 IV Dose | -49.460 nanogram/milliliter | — |
| Cohort 3 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1 | 1 Week post Day 29 SC Dose 3 | -28.055 nanogram/milliliter | Standard Deviation 17.3237 |
Secondary
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 1 IV Dose | -8.570 Ratio | — |
| Cohort 1 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 29 SC Dose 3 | -7.620 Ratio | Standard Deviation 5.3878 |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 1 IV Dose | -16.070 Ratio | — |
| Cohort 2 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 29 SC Dose 3 | -15.285 Ratio | Standard Deviation 6.2807 |
| Cohort 3 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 1 IV Dose | -15.260 Ratio | — |
| Cohort 3 | Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1 | 1 Week post Day 29 SC Dose 3 | -8.368 Ratio | Standard Deviation 6.3951 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
Time frame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Population: The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850 | 407 hour*micrograms/milliliter | Geometric Coefficient of Variation 38.3 |
| Cohort 2 | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850 | 1010 hour*micrograms/milliliter | Geometric Coefficient of Variation 26 |
| Cohort 3 | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850 | 2450 hour*micrograms/milliliter | Geometric Coefficient of Variation 33.6 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
Time frame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Population: The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signfies those participants who were evaluable for this endpoint only and number analyzed signifies those participants who were evaluable for prespecified categories only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 111 hour*micrograms/milliliter | Geometric Coefficient of Variation 58.5 |
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 115 hour*micrograms/milliliter | Geometric Coefficient of Variation 42.2 |
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 115 hour*micrograms/milliliter | Geometric Coefficient of Variation 73.9 |
| Cohort 2 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 350 hour*micrograms/milliliter | Geometric Coefficient of Variation 83.3 |
| Cohort 2 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 383 hour*micrograms/milliliter | Geometric Coefficient of Variation 58.1 |
| Cohort 2 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 367 hour*micrograms/milliliter | Geometric Coefficient of Variation 95.6 |
| Cohort 3 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 1110 hour*micrograms/milliliter | Geometric Coefficient of Variation 49.6 |
| Cohort 3 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 881 hour*micrograms/milliliter | Geometric Coefficient of Variation 104 |
| Cohort 3 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 872 hour*micrograms/milliliter | Geometric Coefficient of Variation 65.5 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
Time frame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Population: The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. As pre-specified, data are presented pooled for all participants who received study drug.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850 | 15 mg | 0.286 Ratio |
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850 | 45 mg | 0.367 Ratio |
| Cohort 1 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850 | 90 mg | 0.368 Ratio |
Secondary
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
Time frame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Population: The Pharmacokinetic (PK) Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, number analyzed signifies those participants who were evaluable for prespecified categories only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | IV Dose | 5.31 micrograms/milliliter | Geometric Coefficient of Variation 29.2 |
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 0.871 micrograms/milliliter | Geometric Coefficient of Variation 43.8 |
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 0.815 micrograms/milliliter | Geometric Coefficient of Variation 52.3 |
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 0.844 micrograms/milliliter | Geometric Coefficient of Variation 75.2 |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 2.41 micrograms/milliliter | Geometric Coefficient of Variation 97.4 |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | IV Dose | 13.5 micrograms/milliliter | Geometric Coefficient of Variation 23.3 |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 2.38 micrograms/milliliter | Geometric Coefficient of Variation 88.8 |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 2.89 micrograms/milliliter | Geometric Coefficient of Variation 59.4 |
| Cohort 3 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 3 | 5.44 micrograms/milliliter | Geometric Coefficient of Variation 145 |
| Cohort 3 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 1 | 8.60 micrograms/milliliter | Geometric Coefficient of Variation 43.5 |
| Cohort 3 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | SC Dose 2 | 6.33 micrograms/milliliter | Geometric Coefficient of Variation 55.5 |
| Cohort 3 | Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3 | IV Dose | 32.4 micrograms/milliliter | Geometric Coefficient of Variation 31.1 |
Secondary
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
Time frame: Baseline up to Day 85
Population: The Immunogenicity Analysis Set included all treated participants who received any study drug and who after the first dose had at least one reportable result in the ADA assay.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | ADA Positive | 2 Participants |
| Cohort 1 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | NAb Positive | 0 Participants |
| Cohort 2 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | ADA Positive | 0 Participants |
| Cohort 2 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | NAb Positive | 0 Participants |
| Cohort 3 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | ADA Positive | 2 Participants |
| Cohort 3 | Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status | NAb Positive | 0 Participants |
Secondary
Percent Change From Baseline in Plasma Concentration of PLP at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 1 IV Dose | -47.906 percent change | — |
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 29 SC Dose 3 | -33.895 percent change | Standard Deviation 42.5254 |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 1 IV Dose | -17.512 percent change | — |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 29 SC Dose 3 | -69.049 percent change | Standard Deviation 16.5385 |
| Cohort 3 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 1 IV Dose | -86.318 percent change | — |
| Cohort 3 | Percent Change From Baseline in Plasma Concentration of PLP at Week 1 | 1 Week post Day 29 SC Dose 3 | -70.515 percent change | Standard Deviation 23.0447 |
Secondary
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 1 IV Dose | -65.270 percent change | — |
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 29 SC Dose 3 | -35.104 percent change | Standard Deviation 15.0384 |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 1 IV Dose | -92.944 percent change | — |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 29 SC Dose 3 | -77.160 percent change | Standard Deviation 16.0636 |
| Cohort 3 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 1 IV Dose | -91.323 percent change | — |
| Cohort 3 | Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1 | 1 Week post Day 29 SC Dose 3 | -60.816 percent change | Standard Deviation 49.7578 |
Secondary
Percent Change From Baseline in Plasma Concentration of PPi at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Population: The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Number analyzed signifies those participants who were evaluable for prespecified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | 1 Week post Day 1 IV Dose | -53.821 percent change | — |
| Cohort 1 | Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | 1 Week post Day 29 SC Dose 3 | -32.740 percent change | Standard Deviation 23.0615 |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | 1 Week post Day 1 IV Dose | -70.956 percent change | — |
| Cohort 2 | Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | 1 Week post Day 29 SC Dose 3 | -55.328 percent change | Standard Deviation 1.7622 |
| Cohort 3 | Percent Change From Baseline in Plasma Concentration of PPi at Week 1 | 1 Week post Day 29 SC Dose 3 | -71.329 percent change | — |