Healthy Volunteer
Conditions
Keywords
Healthy Male, Healthy Female of non child bearing potential
Brief summary
Phase 1 single IV dose study to evaluate safety and tolerability of MEDI4920
Interventions
BIOLOGICALMEDI4920 3 mg
Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.
BIOLOGICALMEDI4920 10 mg
Participants received single IV dose of MEDI4920 10 mg infused on Day 1.
BIOLOGICALMEDI4920 30 mg
Participants received single IV dose of MEDI4920 30 mg infused on Day 1.
BIOLOGICALMEDI4920 100 mg
Participants received single IV dose of MEDI4920 100 mg infused on Day 1.
BIOLOGICALMEDI4920 300 mg
Participants received single IV dose of MEDI4920 300 mg infused on Day 1.
BIOLOGICALMEDI4920 1000 mg
Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.
BIOLOGICALMEDI4920 3000 mg
Participants received single IV dose of MEDI4920 3000 mg infused on Day 1.
OTHERPlacebo
Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy as determined by a responsible study physician based on medical evaluation * Body weight 40 to 100 kg * Body mass index 19.0 to 30.0 kg/m2
Exclusion criteria
* History of allergy or sensitivity to Shellfish or protein based antigens * previous immunization with KLH * previous splenectomy * History of diagnosed or suspected thromboembolic event or coagulation disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | The start of study drug administration (Day 1) to the follow-up period (Day 113) or early discontinuation visit | An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability or incapacity; congenital anomaly or birth defect in the offspring of a participant who received the study drug. A TEAE is defined as the event with onset after the start of infusion (Day 1) to Day 113 or early discontinuation visit inclusive. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The area under the plasma concentration-time curve from time zero to infinity (AUC 0-inf) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI4920 dose. The AUC (0-infinity)/D was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Terminal Elimination Half Life (t1/2) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The maximum observed plasma concentration (Cmax) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Volume of Distribution at Steady-state (Vss) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The volume of distribution at steady-state (Vss) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The volume of distribution based on terminal phase (Vz) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
| Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline (pre-infusion on Day 1) and post-baseline Days 15, 29, 57, and 113 or early discontinuation visit, whichever occurred first | Plasma samples were collected for assessment of anti-drug antibodies (ADA) against MEDI4920. The incidence of positive serum antibodies to MEDI4920 are presented. |
| T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | Day 43 | The T-cell dependent antibody response (TDAR) assay measures the immune response (ie, antibody production) to an introduced antigen, keyhole limpet hemocyanin (KLH). The KLH is a potent immunostimulating protein with an extensive history of safe and effective use in vaccine development and immunological research. TDAR was evaluated by measuring anti-KLH IgG titers at a time point consistent with the expected timing for antibody responses following immunization. The primary time point for the analysis of the TDAR to KLH was Day 43. The data was presented for geometric mean ratio (MEDI4920/placebo) estimated from the dose response model. |
| Systemic Clearance (CL) of MEDI4920 | Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first | The systemic clearance (CL) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3. |
Countries
United Kingdom
Participant flow
Recruitment details
Healthy adult male and female participants were recruited in a blinded manner. The study was conducted at one site in the United Kingdom.
Pre-assignment details
A total of 259 participants were screened of which 200 participants were considered screen failures and the remaining 59 participants were randomized. Out of which, 56 participants were treated
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1. | 12 |
| MEDI4920 3 mg Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1. | 2 |
| MEDI4920 10 mg Participants received single IV dose of MEDI4920 10 mg infused on Day 1. | 2 |
| MEDI4920 30 mg Participants received single IV dose of MEDI4920 30 mg infused on Day 1. | 8 |
| MEDI4920 100 mg Participants received single IV dose of MEDI4920 100 mg infused on Day 1. | 8 |
| MEDI4920 300 mg Participants received single IV dose of MEDI4920 300 mg infused on Day 1. | 8 |
| MEDI4920 1000 mg Participants received single IV dose of MEDI4920 1000 mg infused on Day 1. | 8 |
| MEDI4920 3000 mg Participants received single IV dose of MEDI4920 3000 mg infused on Day 1. | 8 |
| TOTAL Total of all reporting groups | 56 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | MEDI4920 3 mg | MEDI4920 10 mg | MEDI4920 30 mg | MEDI4920 100 mg | MEDI4920 300 mg | MEDI4920 1000 mg | MEDI4920 3000 mg | TOTAL |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.3 Years STANDARD_DEVIATION 8.9 | 27.5 Years STANDARD_DEVIATION 4.9 | 26.0 Years STANDARD_DEVIATION 1.4 | 27.8 Years STANDARD_DEVIATION 12.3 | 28.1 Years STANDARD_DEVIATION 10.1 | 38.4 Years STANDARD_DEVIATION 9.3 | 33.3 Years STANDARD_DEVIATION 9.2 | 32.0 Years STANDARD_DEVIATION 9.8 | 31.8 Years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 2 Participants | 2 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 56 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 2 | 0 / 2 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 10 / 12 | 1 / 2 | 1 / 2 | 5 / 8 | 8 / 8 | 3 / 8 | 5 / 8 | 7 / 8 |
| serious Total, serious adverse events | 1 / 12 | 0 / 2 | 0 / 2 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability or incapacity; congenital anomaly or birth defect in the offspring of a participant who received the study drug. A TEAE is defined as the event with onset after the start of infusion (Day 1) to Day 113 or early discontinuation visit inclusive. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0.
Time frame: The start of study drug administration (Day 1) to the follow-up period (Day 113) or early discontinuation visit
Population: As-treated Population: All participants who received any study drug were included in this population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 10 Participants |
| MEDI4920 3 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 3 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| MEDI4920 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| MEDI4920 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| MEDI4920 30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 8 Participants |
| MEDI4920 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| MEDI4920 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| MEDI4920 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 3000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI4920 3000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 7 Participants |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920
The area under the plasma concentration-time curve from time zero to infinity (AUC 0-inf) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 4.60 microgram*day per milliliter (µg*d/mL) | — |
| MEDI4920 3 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 20.5 microgram*day per milliliter (µg*d/mL) | — |
| MEDI4920 10 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 54.8 microgram*day per milliliter (µg*d/mL) | Standard Deviation 11 |
| MEDI4920 30 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 152 microgram*day per milliliter (µg*d/mL) | Standard Deviation 20.2 |
| MEDI4920 100 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 583 microgram*day per milliliter (µg*d/mL) | Standard Deviation 37.8 |
| MEDI4920 300 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 2090 microgram*day per milliliter (µg*d/mL) | Standard Deviation 394 |
| MEDI4920 1000 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920 | 6640 microgram*day per milliliter (µg*d/mL) | Standard Deviation 547 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920
The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 3.64 microgram*day per milliliter (µg*d/mL) | — |
| MEDI4920 3 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 19.3 microgram*day per milliliter (µg*d/mL) | — |
| MEDI4920 10 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 53.4 microgram*day per milliliter (µg*d/mL) | Standard Deviation 10.9 |
| MEDI4920 30 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 151 microgram*day per milliliter (µg*d/mL) | Standard Deviation 20.2 |
| MEDI4920 100 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 581 microgram*day per milliliter (µg*d/mL) | Standard Deviation 38.3 |
| MEDI4920 300 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 2090 microgram*day per milliliter (µg*d/mL) | Standard Deviation 394 |
| MEDI4920 1000 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920 | 6640 microgram*day per milliliter (µg*d/mL) | Standard Deviation 553 |
Secondary
Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920
The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI4920 dose. The AUC (0-infinity)/D was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 1.53 µg*d/mL/mg | — |
| MEDI4920 3 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 2.05 µg*d/mL/mg | — |
| MEDI4920 10 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 1.83 µg*d/mL/mg | Standard Deviation 0.366 |
| MEDI4920 30 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 1.52 µg*d/mL/mg | Standard Deviation 0.202 |
| MEDI4920 100 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 1.94 µg*d/mL/mg | Standard Deviation 0.126 |
| MEDI4920 300 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 2.09 µg*d/mL/mg | Standard Deviation 0.394 |
| MEDI4920 1000 mg | Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920 | 2.21 µg*d/mL/mg | Standard Deviation 0.182 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MEDI4920
The maximum observed plasma concentration (Cmax) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 1.00 microgram per milliliter (µg/mL) | — |
| MEDI4920 3 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 4.46 microgram per milliliter (µg/mL) | — |
| MEDI4920 10 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 7.97 microgram per milliliter (µg/mL) | Standard Deviation 0.873 |
| MEDI4920 30 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 23.6 microgram per milliliter (µg/mL) | Standard Deviation 2.76 |
| MEDI4920 100 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 85.6 microgram per milliliter (µg/mL) | Standard Deviation 17.6 |
| MEDI4920 300 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 289 microgram per milliliter (µg/mL) | Standard Deviation 58.1 |
| MEDI4920 1000 mg | Maximum Observed Plasma Concentration (Cmax) of MEDI4920 | 960 microgram per milliliter (µg/mL) | Standard Deviation 126 |
Secondary
Percentage of Participants Positive for Anti-drug Antibodies (ADA)
Plasma samples were collected for assessment of anti-drug antibodies (ADA) against MEDI4920. The incidence of positive serum antibodies to MEDI4920 are presented.
Time frame: Baseline (pre-infusion on Day 1) and post-baseline Days 15, 29, 57, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 16.7 Percentage of participants |
| Placebo | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 8.3 Percentage of participants |
| MEDI4920 3 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 3 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 50 Percentage of participants |
| MEDI4920 10 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 10 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 100 Percentage of participants |
| MEDI4920 30 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 30 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 100 Percentage of participants |
| MEDI4920 100 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 100 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 87.5 Percentage of participants |
| MEDI4920 300 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 300 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 37.5 Percentage of participants |
| MEDI4920 1000 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 37.5 Percentage of participants |
| MEDI4920 1000 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 3000 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Baseline ADA positive | 0 Percentage of participants |
| MEDI4920 3000 mg | Percentage of Participants Positive for Anti-drug Antibodies (ADA) | Post-baseline ADA positive | 12.5 Percentage of participants |
Secondary
Systemic Clearance (CL) of MEDI4920
The systemic clearance (CL) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Systemic Clearance (CL) of MEDI4920 | 661 milliliter per day (mL/day) | — |
| MEDI4920 3 mg | Systemic Clearance (CL) of MEDI4920 | 487 milliliter per day (mL/day) | — |
| MEDI4920 10 mg | Systemic Clearance (CL) of MEDI4920 | 564 milliliter per day (mL/day) | Standard Deviation 96.8 |
| MEDI4920 30 mg | Systemic Clearance (CL) of MEDI4920 | 668 milliliter per day (mL/day) | Standard Deviation 90.4 |
| MEDI4920 100 mg | Systemic Clearance (CL) of MEDI4920 | 517 milliliter per day (mL/day) | Standard Deviation 33.5 |
| MEDI4920 300 mg | Systemic Clearance (CL) of MEDI4920 | 494 milliliter per day (mL/day) | Standard Deviation 102 |
| MEDI4920 1000 mg | Systemic Clearance (CL) of MEDI4920 | 454 milliliter per day (mL/day) | Standard Deviation 37.9 |
Secondary
T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration
The T-cell dependent antibody response (TDAR) assay measures the immune response (ie, antibody production) to an introduced antigen, keyhole limpet hemocyanin (KLH). The KLH is a potent immunostimulating protein with an extensive history of safe and effective use in vaccine development and immunological research. TDAR was evaluated by measuring anti-KLH IgG titers at a time point consistent with the expected timing for antibody responses following immunization. The primary time point for the analysis of the TDAR to KLH was Day 43. The data was presented for geometric mean ratio (MEDI4920/placebo) estimated from the dose response model.
Time frame: Day 43
Population: As-treated Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | NA nanogram per milliliter (ng/mL) |
| MEDI4920 3 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.99 nanogram per milliliter (ng/mL) |
| MEDI4920 10 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.96 nanogram per milliliter (ng/mL) |
| MEDI4920 30 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.88 nanogram per milliliter (ng/mL) |
| MEDI4920 100 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.68 nanogram per milliliter (ng/mL) |
| MEDI4920 300 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.42 nanogram per milliliter (ng/mL) |
| MEDI4920 1000 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.22 nanogram per milliliter (ng/mL) |
| MEDI4920 3000 mg | T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration | 0.14 nanogram per milliliter (ng/mL) |
Secondary
Terminal Elimination Half Life (t1/2) of MEDI4920
The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Elimination Half Life (t1/2) of MEDI4920 | 4.41 Day(s) | — |
| MEDI4920 3 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 5.35 Day(s) | — |
| MEDI4920 10 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 5.31 Day(s) | Standard Deviation 2.3 |
| MEDI4920 30 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 5.49 Day(s) | Standard Deviation 1.59 |
| MEDI4920 100 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 8.86 Day(s) | Standard Deviation 1.6 |
| MEDI4920 300 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 9.68 Day(s) | Standard Deviation 1.25 |
| MEDI4920 1000 mg | Terminal Elimination Half Life (t1/2) of MEDI4920 | 10.1 Day(s) | Standard Deviation 1.87 |
Secondary
Volume of Distribution at Steady-state (Vss) of MEDI4920
The volume of distribution at steady-state (Vss) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 3980 milliliter (mL) | — |
| MEDI4920 3 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 3290 milliliter (mL) | — |
| MEDI4920 10 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 4280 milliliter (mL) | Standard Deviation 684 |
| MEDI4920 30 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 5560 milliliter (mL) | Standard Deviation 806 |
| MEDI4920 100 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 5180 milliliter (mL) | Standard Deviation 811 |
| MEDI4920 300 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 5450 milliliter (mL) | Standard Deviation 1150 |
| MEDI4920 1000 mg | Volume of Distribution at Steady-state (Vss) of MEDI4920 | 4900 milliliter (mL) | Standard Deviation 715 |
Secondary
Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920
The volume of distribution based on terminal phase (Vz) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.
Time frame: Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Population: As-treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 4130 milliliter (mL) | — |
| MEDI4920 3 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 3760 milliliter (mL) | — |
| MEDI4920 10 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 4080 milliliter (mL) | Standard Deviation 1090 |
| MEDI4920 30 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 5230 milliliter (mL) | Standard Deviation 1360 |
| MEDI4920 100 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 6590 milliliter (mL) | Standard Deviation 1160 |
| MEDI4920 300 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 6880 milliliter (mL) | Standard Deviation 1520 |
| MEDI4920 1000 mg | Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920 | 6600 milliliter (mL) | Standard Deviation 1190 |