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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005450-19 | EudraCT Number |
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| Name | Class |
|---|---|
| Amgen | INDUSTRY |
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To evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma.
The primary objective is to evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma. The secondary objective is to evaluate the safety and tolerability of MEDI9929 and to evaluate the immunogenicity of MEDI9929 (AMG 157). The exploratory objective is to evaluate the effect of MEDI9929 (AMG 157) on pulmonary function
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MEDI9929, 140 mg, Cohort 1 (12 to 14 years) | Experimental | On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 12 to 14 years of age. |
|
| MEDI9929, 140 mg, Cohort 2 (15 to 17 years) | Experimental | On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 15 to 17 years of age. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI9929, 140 mg | Drug | On Day 1, two MEDI9929 subcutaneous injection of 70 mg each were given into the anterior aspect of one thigh immediately followed by the second injection into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants of 12 to 17 years of age. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | The pharmacokinetic (PK) parameter AUC (0 to infinity) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) | The PK parameter AUC (0-t) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Dose-normalized AUC (0-infinity) (AUC [0 Infinity]/D) | The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Maximum Observed Serum Concentration (Cmax) | The PK parameter Cmax was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Dose-normalized Cmax (Cmax/D) | The Cmax/D is the maximum observed concentration post dose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events | An adverse event (AE) is any unfavorable and unintended sign, 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 any AE resulting in any of the following outcomes such as death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. A TEAE is defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0 |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rene van der Merwe, MBChB, MSc, FFPM | MedImmune LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Kielce | 25-040 | Poland | |||
| Research Site |
A total of 26 participants were screened, out of these, 21 subjects were randomized and completed the study at 2 investigative sites in Poland.
Adolescent participants (12 to 17 years, inclusive) with mild to moderate asthma were recruited in an open-label fashion to receive a single-dose of MEDI9929 (also known as tezepelumab or AMG 157) at two study centers in Poland from Sep 2015 to May 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | MEDI9929, 140 mg, (12 to 14 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
| FG001 | MEDI9929, 140 mg, (15 to 17 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MEDI9929, 140 mg, (12 to 14 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
| BG001 | MEDI9929, 140 mg, (15 to 17 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | The pharmacokinetic (PK) parameter AUC (0 to infinity) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population: All participants who received MEDI9929 and have a sufficient number of serum concentration measurements for computing PK parameters. | Posted | Mean | Standard Deviation | μg*day/mL | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
From the start of study drug administration up to end of followup period, assessed up to Day 85.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MEDI9929, 140 mg, (12 to 14 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rene van der Merwe, Senior Director, Clinical Development, Respiratory, and Inflammation | MedImmune, LLC | 301-398-0000 |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C000622721 | tezepelumab |
| D007279 | Injections, Subcutaneous |
| ID | Term |
|---|---|
| D007267 | Injections |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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|
|
| Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Time to Reach Cmax (Tmax) | The Tmax is the time to maximum observed serum concentration of MEDI9929. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Terminal Phase Elimination Half Life (t1/2,z) | The t½,z is the time measured for the serum drug concentration of MEDI9929 to decrease by one half. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Apparent Clearance (CL/F) | The PK parameter CL/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| Apparent Steady-state Volume of Distribution (Vss/F) | The PK parameter Vss/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
| From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
| Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings | Vital signs (blood pressure, temperature, pulse, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
| Treatment-emergent Adverse Events Related to Laboratory Parameters | Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell count with differential, red blood cell count, hematocrit, hemoglobin and platelet count); serum chemistry: calcium, chloride, potassium, sodium, bicarbonate, aspartate transaminase, alanine transaminase, albumin, uric acid, creatinine, total bilirubin, glucose, alkaline phosphatase, blood urea nitrogen, total protein, and gamma glutamyl transferase; and urinalysis (nitrites, protein, glucose, ketones, urine drug screen, blood, and bilirubin). Number of participants with TEAEs related to laboratory evaluations were reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
| Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Computerized triplicate 12-lead ECGs as well as Qualitative 12-lead ECGs were obtained during the study. ECG parameters included heart rate, PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with TEAEs related to ECG after the start of study drug were to be reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
| Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at Any Visit | Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9929. The incidence rate of positive serum antibodies to MEDI9929 were presented. | Days 1 (predose), 29, 57 and 85 |
| Lodz |
| 71-329 |
| Poland |
| Research Site | Wroclaw | 51-162 | Poland |
| Research Site | Wroclaw | 53-201 | Poland |
| BG002 | TOTAL | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. |
|
|
| Primary | Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) | The PK parameter AUC (0-t) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | μg*day/mL | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Dose-normalized AUC (0-infinity) (AUC [0 Infinity]/D) | The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | μg*day/mL/mg | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Maximum Observed Serum Concentration (Cmax) | The PK parameter Cmax was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | μg/mL | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Dose-normalized Cmax (Cmax/D) | The Cmax/D is the maximum observed concentration post dose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | μg/mL/mg | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Time to Reach Cmax (Tmax) | The Tmax is the time to maximum observed serum concentration of MEDI9929. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Median | Full Range | Day | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Terminal Phase Elimination Half Life (t1/2,z) | The t½,z is the time measured for the serum drug concentration of MEDI9929 to decrease by one half. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | Day | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Apparent Clearance (CL/F) | The PK parameter CL/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | Liter/day | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Primary | Apparent Steady-state Volume of Distribution (Vss/F) | The PK parameter Vss/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | PK Population | Posted | Mean | Standard Deviation | Liter | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. |
|
|
|
| Secondary | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events | An adverse event (AE) is any unfavorable and unintended sign, 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 any AE resulting in any of the following outcomes such as death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. A TEAE is defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0 | As-treated Population: All participants who received any treatment of MEDI9929. | Posted | Number | Participants | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
|
|
|
| Secondary | Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings | Vital signs (blood pressure, temperature, pulse, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported. | As-treated Population | Posted | Number | Participants | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
|
|
|
| Secondary | Treatment-emergent Adverse Events Related to Laboratory Parameters | Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell count with differential, red blood cell count, hematocrit, hemoglobin and platelet count); serum chemistry: calcium, chloride, potassium, sodium, bicarbonate, aspartate transaminase, alanine transaminase, albumin, uric acid, creatinine, total bilirubin, glucose, alkaline phosphatase, blood urea nitrogen, total protein, and gamma glutamyl transferase; and urinalysis (nitrites, protein, glucose, ketones, urine drug screen, blood, and bilirubin). Number of participants with TEAEs related to laboratory evaluations were reported. | As-treated Population | Posted | Number | Participants | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
|
|
|
| Secondary | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Computerized triplicate 12-lead ECGs as well as Qualitative 12-lead ECGs were obtained during the study. ECG parameters included heart rate, PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with TEAEs related to ECG after the start of study drug were to be reported. | As-treated Population | Posted | Number | Participants | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 |
|
|
|
| Secondary | Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at Any Visit | Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9929. The incidence rate of positive serum antibodies to MEDI9929 were presented. | As-treated Population. Neutralizing antibody was tested only for the positive ADA samples. Combined immunogenicity data is presented for all participants (that is 12 to 17 years of age). n= Number of participants analyzed for this outcome measure at the given time point. | Posted | Number | Participants | Days 1 (predose), 29, 57 and 85 |
|
|
|
| 0 |
| 11 |
| 4 |
| 11 |
| EG001 | MEDI9929, 140 mg, (15 to 17 Years) | On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | 0 | 10 | 4 | 10 |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute sinusitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
| Post-baseline: Positive neutralizing antibody, n=1 |
|