Safety and Tolerability of MEDI9314 as Single Ascending Dose in Healthy Subjects

Study Overview
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Brief Summary
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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
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This is a phase I study to assess the safety, tolerability pharmacokinetics, and immunogenicity of MEDI9314 following single dose administration to healthy subjects

Official Title
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A Phase 1a Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI9314 in Healthy Adult Subjects

Conditions
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Safety, Healthy Subjects

Intervention / Treatment
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* Drug: MEDI9314
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Age 18 through 50 years at the time of screening. Female subjects must be of non-childbearing potential. Nonsterilized males who are sexually active with a female partner of childbearing potential must use condom and spermicide. Body mass index of 19.0 through 32.0 kg/m2 at screening. No clinically significant abnormality on the basis of medical/medication history or physical examination. Negative drugs of abuse (DOA). Able and willing to comply with the requirements of the protocol and complete the study until the end of the safety follow up period. For the Japanese Cohort, both of the subject's parents and both sets of grandparents must be Japanese. Exclusion Criteria: 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. Concurrent enrollment in another clinical study involving any treatment. Individuals who are legally institutionalized. Receipt of > 2 marketed or investigational biologic agents. Receipt of an investigational biologic agent within 4 months or 5 half-lives prior to screening, whichever is longer. Receipt of any investigational non biologic agent within 3 months or 5 half lives prior to screening, whichever is longer. 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. Known history of allergy or reaction to any component of the investigational product formulation. History of anaphylaxis following any biologic therapy. Any clinically relevant abnormal findings in physical examination ECG, vital signs, and laboratory parameters. Positive tuberculosis (TB) test (QuantiFERON®-TB Gold In-tube). Positive hepatitis B surface antigen, hepatitis C virus antibody or HIV test at screening. Receipt of live attenuated vaccines 30 days prior to the date of screening. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|
| Experimental: Cohort 2<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|
| Experimental: Cohort 3<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|
| Experimental: Cohort 4<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|
| Experimental: Japanese Cohort<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|
| Experimental: Cohort 5<br>single dose of MEDI9314 or placebo | Drug: MEDI9314<br>* single dose of MEDI9314<br>Drug: placebo<br>* single dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From the start of study drug administration upto Day 240 | 
| Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs | TEAEs observed in participants with clinically significant ECG abnormalities were reported. | From the start of study drug administration upto Day 240 | 
| 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. | From the start of study drug administration upto Day 240 | 
| Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Adverse events observed in participants with clinically significant physical abnormalities were assessed. | From the start of study drug administration upto Day 240 | 
| 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. | From the start of study drug administration upto Day 240 | 
| 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. | From the start of study drug administration upto Day 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| Maximum Observed Serum Drug Concentration (Cmax) of MEDI9314 | The maximum observed serum drug concentration 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 | 
| Time to Maximum Observed Serum Drug Concentration (Tmax) of MEDI9314 | The time to maximum observed serum drug concentration 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 (t1/2) of MEDI9314 | Terminal phase elimination half-life 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 | 
| 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. | Baseline (Day 1 [predose]) and Day 240 | 
| 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. | Baseline (Day 1 [predose]) and Day 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI9314, Safety, Tolerability, Pharmacokinetics, Immunogenicity