Clinical trial NCT02388347: A Study to Assess the Safety of MEDI7836 in Healthy Adults.
Official title: A Phase 1a, Randomised, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI7836 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Vital signs, ECG, and laboratory parameters within normal range at screening and Day -1
2. Negative alcohol and drug screen at screening and Day -1
3. Able and willing to comply with the requirements of the protocol
4. Females subjects must have been surgically sterilised or be postmenopausal
5. 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:

1. Concurrent enrolment in another clinical study where the subject is receiving an investigational product
2. Individuals who are legally institutionalised
3. Receipt of any marketed or investigational biologic agent within 4 months
4. Receipt of any investigational non-biologic agent within 3 months or 5 half-lives prior to screening, whichever is longer
5. Use of any medication (prescription or over the counter, including herbal remedies) within 14 days or 5 half-lives of Day 1,
6. Known history of allergy or reaction to any component of the investigational product formulation
7. History of anaphylaxis following any biologic therapy
8. History of chronic alcohol or drug abuse within 12 months prior to screening,
9. Presence of a positive drug or alcohol screen at screening and Day -1.
10. Current smoker, or history of smoking within 6 months of screening
11. Pregnant or breastfeeding women
12. 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
13. Any clinically relevant abnormal findings in physical examination, ECG, vital signs, haematology, clinical chemistry or urinalysis during screening or Day -1,
14. History of any known primary immunodeficiency disorder or use of immunosuppressive medication within 12 months of screening
15. History of a clinically significant infection requiring antibiotics or antiviral medication from 30 days prior to screening, up to and including Day 1
16. 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
17. 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
18. Positive tuberculosis (TB) test (Quantiferon-TB Gold) at screening or TB requiring treatment within the 12 months prior to the screening visit
19. Positive hepatitis B surface antigen, hepatitis B anti-core antibody, or hepatitis C virus antibody serology at screening.
20. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enter the study.
21. A positive human immunodeficiency virus test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report
22. 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)
23. Major surgery within 8 weeks prior to screening, or planed in-patient surgery or hospitalisation during the study period
24. 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

Primary outcomes:
measure: Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Study Drug Administration to 281 Days Postdose
measure: Number of Participants With Injection Site Reactions
timeFrame: From Study Drug Administration to 281 Days Postdose
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events
timeFrame: From Study Drug Administration to 281 Days Postdose
measure: Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events
timeFrame: From Study Drug Administration to 281 Days Postdose
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
timeFrame: From Study Drug Administration to 281 Days Postdose
Secondary outcomes:
measure: Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Maximum Observed Serum Concentration (Cmax) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Apparent Systemic Clearance (CL/F) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Terminal Phase Elimination Half Life (T1/2) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836
timeFrame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
measure: Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836
timeFrame: Predose on Day 1 to 281 days Postdose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Parexel
name: Annelize Koch, MD
role: PRINCIPAL_INVESTIGATOR
References: