A Study to Assess the Safety of MEDI7836 in Healthy Adults.

Study Overview
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Brief Summary
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To assess the safety of a single ascending dose of MEDI7836 in healthy adult male subjects and healthy adult female subjects of non-childbearing potential.

Detailed Description
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This is a Phase 1a, randomised, blinded (the investigator and subject will be blinded to treatment assignment and sponsor will be unblinded to treatment assignment), placebo-controlled study to evaluate the safety of single-ascending SC doses of MEDI7836 in healthy adult males subjects and healthy adult female subjects of non-childbearing potential. The study will be conducted at a single site in the United Kingdom (UK). Four dosing cohorts of MEDI7836 or placebo are planned for this study for a total of 32 subjects (24 subjects receiving MEDI7836, 8 subjects receiving placebo).

Official Title
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A Phase 1a, Randomised, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI7836 in Healthy Adults

Conditions
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Healthy Adults

Intervention / Treatment
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* Drug: Placebo SC
* Biological: MEDI7836 Dose 1
* Biological: MEDI7836 Dose 2
* Biological: MEDI7836 Dose 3
* Biological: MEDI7836 Dose 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vital signs, ECG, and laboratory parameters within normal range at screening and Day -1 Negative alcohol and drug screen at screening and Day -1 Able and willing to comply with the requirements of the protocol Females subjects must have been surgically sterilised or be postmenopausal Nonsterilised males who are sexually active with a female partner of childbearing potential or a female partner who has been surgically sterilised by bilateral tubal ligation must use a condom with spermicide with their partner from screening until the end of the study follow-up period Exclusion Criteria: Concurrent enrolment in another clinical study where the subject is receiving an investigational product Individuals who are legally institutionalised Receipt of any marketed or investigational biologic agent within 4 months 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, Known history of allergy or reaction to any component of the investigational product formulation History of anaphylaxis following any biologic therapy History of chronic alcohol or drug abuse within 12 months prior to screening, Presence of a positive drug or alcohol screen at screening and Day -1. Current smoker, or history of smoking within 6 months of screening Pregnant or breastfeeding women Any active medical or psychiatric condition or other reason which, in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study Any clinically relevant abnormal findings in physical examination, ECG, vital signs, haematology, clinical chemistry or urinalysis during screening or Day -1, History of any known primary immunodeficiency disorder or use of immunosuppressive medication within 12 months of screening History of a clinically significant infection requiring antibiotics or antiviral medication from 30 days prior to screening, up to and including Day 1 Diagnosis of a helminth parasitic infection within 6 months prior to screening that has not been treated with, or has failed to respond to, standard of care therapy History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening Positive tuberculosis (TB) test (Quantiferon-TB Gold) at screening or TB requiring treatment within the 12 months prior to the screening visit Positive hepatitis B surface antigen, hepatitis B anti-core antibody, or hepatitis C virus antibody serology at screening. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enter the study. A positive human immunodeficiency virus test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report Evidence of active liver disease, including jaundice or aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase greater than twice the upper limit of normal (ULN) Major surgery within 8 weeks prior to screening, or planed in-patient surgery or hospitalisation during the study period Receipt of live attenuated vaccines 30 days prior to the date of screening Where participation in the study would result in donation of blood or blood products in excess of 500 mL within an 8-week period

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a single-dose of Placebo subcutaneous (SC) injection on Day 1. | Drug: Placebo SC<br>* Participants will receive a single-dose of Placebo subcutaneous (SC) injection on Day 1.<br>|
| Experimental: MEDI7836 Dose 1<br>Participants will receive a single-dose of MEDI7836 Dose 1 SC injection on Day 1. | Biological: MEDI7836 Dose 1<br>* Participants will receive a single-dose of MEDI7836 Dose 1 SC injection on Day 1.<br>|
| Experimental: MEDI7836 Dose 2<br>Participants will receive a single-dose of MEDI7836 Dose 2 SC injection on Day 1. | Biological: MEDI7836 Dose 2<br>* Participants will receive a single-dose of MEDI7836 Dose 2 SC injection on Day 1.<br>|
| Experimental: MEDI7836 Dose 3<br>Participants will receive a single-dose of MEDI7836 Dose 3 SC injection on Day 1. | Biological: MEDI7836 Dose 3<br>* Participants will receive a single-dose of MEDI7836 Dose 3 SC injection on Day 1.<br>|
| Experimental: MEDI7836 Dose 4<br>Participants will receive a single-dose of MEDI7836 Dose 4 SC injection on Day 1. | Biological: MEDI7836 Dose 4<br>* Participants will receive a single-dose of MEDI7836 Dose 4 SC injection on Day 1.<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) | Any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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/incapacity; congenital anomaly/birth defect in the offspring of a participant who received MEDI7836. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pretreatment state. | From Study Drug Administration to 281 Days Postdose | 
| Number of Participants With Injection Site Reactions | Participants were evaluated for manifestations of injection site reactions. | From Study Drug Administration to 281 Days Postdose | 
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent adverse events between first dose of study drug and Day 281 after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed. | From Study Drug Administration to 281 Days Postdose | 
| Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | Vital sign parameters included blood pressure, temperature, pulse rate, respiratory rate and weight. Physical examination included assessment of general appearance, weight, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, abdominal system, and nervous system. Criteria for abnormal physical findings was based on investigator's discretion. TEAEs were present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug until Day 281 after the last dose of study drug. | From Study Drug Administration to 281 Days Postdose | 
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | AEs observed in participants with clinically significant ECG abnormalities were assessed. ECG parameters included heart rate, RR, PR, QRS, QT and QTc intervals. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pre-treatment state. | From Study Drug Administration to 281 Days Postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 extrapolated to infinity (AUC0-inf). | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 to the last quantifiable data point (AUC0-t). | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Maximum Observed Serum Concentration (Cmax) of MEDI7836 | The Cmax is the maximum observed serum concentration of study drug. | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Apparent Systemic Clearance (CL/F) of MEDI7836 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum. | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | The Tmax is defined as actual sampling time to reach maximum observed MEDI7836 concentration. | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | The apparent volume of distribution of MEDI7836 after a single dose, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz). | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | 
| Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study. | Predose on Day 1 to 281 days Postdose |