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

Phase 1

Completed

Conditions: Healthy Adults

Interventions: Biological: MEDI7836 Dose 1
Biological: MEDI7836 Dose 2
Drug: Placebo SC
Biological: MEDI7836 Dose 3
Biological: MEDI7836 Dose 4

Registration Number: NCT02388347

Lead Sponsor: MedImmune LLC

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 79

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI7836 Dose 1	MEDI7836 Dose 1	Participants will receive a single-dose of MEDI7836 Dose 1 SC injection on Day 1.
MEDI7836 Dose 2	MEDI7836 Dose 2	Participants will receive a single-dose of MEDI7836 Dose 2 SC injection on Day 1.
Placebo	Placebo SC	Participants will receive a single-dose of Placebo subcutaneous (SC) injection on Day 1.
MEDI7836 Dose 3	MEDI7836 Dose 3	Participants will receive a single-dose of MEDI7836 Dose 3 SC injection on Day 1.
MEDI7836 Dose 4	MEDI7836 Dose 4	Participants will receive a single-dose of MEDI7836 Dose 4 SC injection on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	From Study Drug Administration to 281 Days Postdose	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.
Number of Participants With Injection Site Reactions	From Study Drug Administration to 281 Days Postdose	Participants were evaluated for manifestations of injection site reactions.
Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events	From Study Drug Administration to 281 Days Postdose	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.
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events	From Study Drug Administration to 281 Days Postdose	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.
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events	From Study Drug Administration to 281 Days Postdose	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.

Secondary Outcome Measures

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