Healthy Subjects, Safety
Conditions
Keywords
MEDI9314, Safety, Tolerability, Pharmacokinetics, Immunogenicity
Brief summary
This is a phase 1a randomized, blinded, placebo-controlled, single-ascending dose study to assess the safety and tolerability of MEDI9314 in healthy adult subjects
Detailed description
This is a phase I study to assess the safety, tolerability pharmacokinetics, and immunogenicity of MEDI9314 following single dose administration to healthy subjects
Interventions
DRUGMEDI9314
single dose of MEDI9314
DRUGplacebo
single dose of placebo
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Written informed consent. 2. Age 18 through 50 years at the time of screening. 3. Female subjects must be of non-childbearing potential. 4. Nonsterilized males who are sexually active with a female partner of childbearing potential must use condom and spermicide. 5. Body mass index of 19.0 through 32.0 kg/m2 at screening. 6. No clinically significant abnormality on the basis of medical/medication history or physical examination. 7. Negative drugs of abuse (DOA). 8. Able and willing to comply with the requirements of the protocol and complete the study until the end of the safety follow up period. 9. For the Japanese Cohort, both of the subject's parents and both sets of grandparents must be Japanese.
Exclusion criteria
1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. 2. Concurrent enrollment in another clinical study involving any treatment. 3. Individuals who are legally institutionalized. 4. Receipt of \> 2 marketed or investigational biologic agents. 5. Receipt of an investigational biologic agent within 4 months or 5 half-lives prior to screening, whichever is longer. 6. Receipt of any investigational non biologic agent within 3 months or 5 half lives prior to screening, whichever is longer. 7. Use of any medication (prescription or over the counter, including herbal remedies) within 14 days or 5 half lives of Day 1, whichever is longer, unless in the opinion of the investigator and medical monitor the medication will not interfere with the study procedures or compromise subject safety. 8. Known history of allergy or reaction to any component of the investigational product formulation. 9. History of anaphylaxis following any biologic therapy. 10. Any clinically relevant abnormal findings in physical examination ECG, vital signs, and laboratory parameters. 11. Positive tuberculosis (TB) test (QuantiFERON®-TB Gold In-tube). 12. Positive hepatitis B surface antigen, hepatitis C virus antibody or HIV test at screening. 13. Receipt of live attenuated vaccines 30 days prior to the date of screening. 14. Where donation of blood or blood products was in excess of 500 mL within an 8-week period in the 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From the start of study drug administration upto Day 240 | An adverse event is any unfavourable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with use of medicinal product, whether or not considered related to medicinal product. Serious adverse event is any AE that resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are 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 and up to Day 240. |
| Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | From the start of study drug administration upto Day 240 | TEAEs observed in participants with clinically significant ECG abnormalities were reported. |
| Number of Participants With Vital Signs Abnormalities Reported as TEAEs | From the start of study drug administration upto Day 240 | Vital sign parameters included blood pressure, heart rate, and temperature. TEAEs observed in participants with clinically significant vital signs abnormalities were reported. |
| Number of Participants With Physical Examination Abnormalities Reported as TEAEs | From the start of study drug administration upto Day 240 | Adverse events observed in participants with clinically significant physical abnormalities were assessed. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | From the start of study drug administration upto Day 240 | An abnormal laboratory finding which required an action or medical intervention by the investigator, or a finding judged by the investigator as medically significant should be reported as an adverse event. Laboratory evaluation (haematology, serum chemistry and urinalysis) of blood and urine samples were performed. |
| Number of Participants With TEAEs Related to Injection Site Reactions | From the start of study drug administration upto Day 240 | Adverse events of special interest observed in participants with clinically significant injection site reaction were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240 | The area under the serum drug concentration versus time curves from zero to infinity of MEDI9314. |
| Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline (Day 1 [predose]) and Day 240 | Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9314. The number of participants with positive serum antibodies to MEDI9314 were presented. |
| Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240 | The area under the serum drug concentration versus time curve, to last quantifiable time point of MEDI9314. |
| Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240 | The maximum observed serum drug concentration of MEDI9314. |
| Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240 | The time to maximum observed serum drug concentration of MEDI9314. |
| Serum Concentrations of MEDI9314 | Baseline (Day 1 [predose]) and Day 240 | Baseline indicates the last assessment prior to first dose. For this study, the lower limit of quantification (LLOQ) for MEDI9314 serum concentrations were 19.53 μg/mL. Where serum concentrations were below this value, a serum concentration of 9.770 μg/mL was imputed. |
| Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240 | Terminal phase elimination half-life of MEDI9314 |
Countries
United Kingdom, United States
Participant flow
Recruitment details
The study was conducted from 18Feb2016 to 12Jun2017 in United States and United Kingdom.
Pre-assignment details
A total of 124 participants were enrolled in the study; of which 80 participants were screen failures. Forty-four participants were randomized to MEDI9314 or placebo in 7 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single subcutaneous (SC) or intravenous (IV) (infused using a syringe infusion pump over 60 to 90 minutes) dose of placebo matched to MEDI9314 on Day 1. | 12 |
| Cohort 1 Participants received a single SC injection of MEDI9314 45 milligram (mg) on Day 1. | 4 |
| Cohort 2 Participants received a single SC injection of MEDI9314 150 mg on Day 1. | 4 |
| Cohort 3 Participants received a single SC injection of MEDI9314 300 mg on Day 1. | 6 |
| Cohort 4 Participants from Japan received a single SC injection of MEDI9314 300 mg on Day 1 | 6 |
| Cohort 5 Participants received a single IV infusion of MEDI9314 300 mg using a syringe infusion pump over 60 to 90 minutes on Day 1. All participants in this group did not receive the complete planned dose as per protocol. The error in operating the infusion pump resulted in receiving a dose of 247.5 mg instead of the intended 300 mg dose. | 6 |
| Cohort 6 Participants received a single IV infusion of MEDI9314 450 mg using a syringe infusion pump over 60 to 90 minutes on Day 1. | 6 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.8 Years STANDARD_DEVIATION 10.2 | 32.0 Years STANDARD_DEVIATION 12.1 | 28.0 Years STANDARD_DEVIATION 5.1 | 32.0 Years STANDARD_DEVIATION 8.6 | 35.0 Years STANDARD_DEVIATION 5.3 | 31.2 Years STANDARD_DEVIATION 8.2 | 36.0 Years STANDARD_DEVIATION 10.5 | 33.0 Years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 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 |
| Race (NIH/OMB) White | 8 Participants | 1 Participants | 4 Participants | 6 Participants | 0 Participants | 4 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 44 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 8 / 12 | 4 / 4 | 2 / 4 | 5 / 6 | 4 / 6 | 5 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
An abnormal laboratory finding which required an action or medical intervention by the investigator, or a finding judged by the investigator as medically significant should be reported as an adverse event. Laboratory evaluation (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 1 Participants |
| Cohort 1 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Cohort 1 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
| Cohort 2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Cohort 2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
| Cohort 3 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Cohort 3 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
| Cohort 4 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 1 Participants |
| Cohort 4 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
| Cohort 5 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Cohort 5 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
| Cohort 6 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participants |
| Cohort 6 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Transaminases increased | 0 Participants |
Primary
Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs
TEAEs observed in participants with clinically significant ECG abnormalities were reported.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 1 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 2 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 3 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 4 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 5 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 6 | Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | 0 Participants |
Primary
Number of Participants With Physical Examination Abnormalities Reported as TEAEs
Adverse events observed in participants with clinically significant physical abnormalities were assessed.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 1 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 2 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 3 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 4 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 5 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 6 | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | 0 Participants |
Primary
Number of Participants With TEAEs Related to Injection Site Reactions
Adverse events of special interest observed in participants with clinically significant injection site reaction were assessed.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 1 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 1 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 1 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Placebo | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 2 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 4 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Cohort 1 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 1 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 1 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 1 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 1 Participants |
| Cohort 2 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 5 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 1 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Cohort 3 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 4 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 4 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 1 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 1 Participants |
| Cohort 5 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 1 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site warmth | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site bruising | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site erythema | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site bruising | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pruritus | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site erythema | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Infusion site pruritus | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site pain | 0 Participants |
| Cohort 6 | Number of Participants With TEAEs Related to Injection Site Reactions | Injection site induration | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event is any unfavourable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with use of medicinal product, whether or not considered related to medicinal product. Serious adverse event is any AE that resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are 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 and up to Day 240.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 8 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 4 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 | 2 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 | 5 Participants |
| Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
Primary
Number of Participants With Vital Signs Abnormalities Reported as TEAEs
Vital sign parameters included blood pressure, heart rate, and temperature. TEAEs observed in participants with clinically significant vital signs abnormalities were reported.
Time frame: From the start of study drug administration upto Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 1 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 2 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 3 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 1 Participants |
| Cohort 4 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 5 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
| Cohort 6 | Number of Participants With Vital Signs Abnormalities Reported as TEAEs | 0 Participants |
Secondary
Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314
The area under the serum drug concentration versus time curves from zero to infinity of MEDI9314.
Time frame: Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Population: Pharmacokinetic (PK) population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters. The Number Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 3.01 µg*d/mL | — |
| Cohort 1 | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 68.8 µg*d/mL | Standard Deviation 47.3 |
| Cohort 2 | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 179 µg*d/mL | Standard Deviation 105 |
| Cohort 3 | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 264 µg*d/mL | Standard Deviation 159 |
| Cohort 4 | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 668 µg*d/mL | Standard Deviation 132 |
| Cohort 5 | Area Under the Serum Drug Concentration Versus Time Curves From Zero to Infinity (AUC 0-inf) of MEDI9314 | 1440 µg*d/mL | Standard Deviation 126 |
Secondary
Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast)
The area under the serum drug concentration versus time curve, to last quantifiable time point of MEDI9314.
Time frame: Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Population: The PK population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters. The Number Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 2.94 μg*d/mL | — |
| Cohort 1 | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 68.6 μg*d/mL | Standard Deviation 47.3 |
| Cohort 2 | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 178 μg*d/mL | Standard Deviation 105 |
| Cohort 3 | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 264 μg*d/mL | Standard Deviation 159 |
| Cohort 4 | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 667 μg*d/mL | Standard Deviation 132 |
| Cohort 5 | Area Under the Serum Drug Concentration Versus Time Curve, to Last Quantifiable Time Point (AUClast) | 1439 μg*d/mL | Standard Deviation 126 |
Secondary
Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314
The maximum observed serum drug concentration of MEDI9314.
Time frame: Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Population: PK population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 0.425 µg/mL | Standard Deviation 0.367 |
| Cohort 1 | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 5.44 µg/mL | Standard Deviation 2.77 |
| Cohort 2 | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 10.4 µg/mL | Standard Deviation 5.63 |
| Cohort 3 | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 14.1 µg/mL | Standard Deviation 8.87 |
| Cohort 4 | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 79.0 µg/mL | Standard Deviation 14.8 |
| Cohort 5 | Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | 108 µg/mL | Standard Deviation 9.99 |
Secondary
Number of Participants Positive for Anti-Drug Antibodies to MEDI9314
Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9314. The number of participants with positive serum antibodies to MEDI9314 were presented.
Time frame: Baseline (Day 1 [predose]) and Day 240
Population: As-treated population included participants who received any study drug and summarized according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Placebo | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 0 Participants |
| Cohort 1 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Cohort 1 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 0 Participants |
| Cohort 2 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Cohort 2 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 0 Participants |
| Cohort 3 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Cohort 3 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 2 Participants |
| Cohort 4 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Cohort 4 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 1 Participants |
| Cohort 5 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 1 Participants |
| Cohort 5 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 1 Participants |
| Cohort 6 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Baseline ADA positive | 0 Participants |
| Cohort 6 | Number of Participants Positive for Anti-Drug Antibodies to MEDI9314 | Day 240- ADA positive | 1 Participants |
Secondary
Serum Concentrations of MEDI9314
Baseline indicates the last assessment prior to first dose. For this study, the lower limit of quantification (LLOQ) for MEDI9314 serum concentrations were 19.53 μg/mL. Where serum concentrations were below this value, a serum concentration of 9.770 μg/mL was imputed.
Time frame: Baseline (Day 1 [predose]) and Day 240
Population: PK population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters. The Number Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentrations of MEDI9314 | Baseline | 21.495 μg/mL | Standard Deviation 14.79 |
| Placebo | Serum Concentrations of MEDI9314 | Day 240 | 23.432 μg/mL | Standard Deviation 20.738 |
| Cohort 1 | Serum Concentrations of MEDI9314 | Baseline | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 1 | Serum Concentrations of MEDI9314 | Day 240 | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 2 | Serum Concentrations of MEDI9314 | Baseline | 22.577 μg/mL | Standard Deviation 31.37 |
| Cohort 2 | Serum Concentrations of MEDI9314 | Day 240 | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 3 | Serum Concentrations of MEDI9314 | Baseline | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 3 | Serum Concentrations of MEDI9314 | Day 240 | 13.167 μg/mL | Standard Deviation 8.32 |
| Cohort 4 | Serum Concentrations of MEDI9314 | Baseline | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 4 | Serum Concentrations of MEDI9314 | Day 240 | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 5 | Serum Concentrations of MEDI9314 | Baseline | 9.770 μg/mL | Standard Deviation 0 |
| Cohort 5 | Serum Concentrations of MEDI9314 | Day 240 | 14.573 μg/mL | Standard Deviation 11.766 |
Secondary
Terminal Phase Elimination Half-life (t1/2) of MEDI9314
Terminal phase elimination half-life of MEDI9314
Time frame: Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Population: The PK population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters. The Number Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 1.74 Day | — |
| Cohort 1 | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 3.55 Day | Standard Deviation 0.685 |
| Cohort 2 | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 4.72 Day | Standard Deviation 0.998 |
| Cohort 3 | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 5.03 Day | Standard Deviation 1.13 |
| Cohort 4 | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 7.31 Day | Standard Deviation 1.29 |
| Cohort 5 | Terminal Phase Elimination Half-life (t1/2) of MEDI9314 | 8.95 Day | Standard Deviation 1.14 |
Secondary
Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314
The time to maximum observed serum drug concentration of MEDI9314.
Time frame: Day 1 (predose); at the end of infusion (for IV groups); 24, 48, 72, and 96 hours post dose; and on Days 8, 10, 15, 22, 29, 36, 43, 57, 85, 113, 141, 197, and 240
Population: PK population included all participants in the as-treated population who received MEDI9314 and who have detectable post-dosing MEDI9314 serum concentrations for accurate estimation of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 4.00 Day |
| Cohort 1 | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 8.07 Day |
| Cohort 2 | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 5.52 Day |
| Cohort 3 | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 5.51 Day |
| Cohort 4 | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 0.04 Day |
| Cohort 5 | Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | 0.04 Day |