A Phase 1/2a Clinical Study to Evaluate the Efficacy of MEDI8852 in the Treatment of Influenza in Adults Challenged With a Wild-Type Influenza Strain
Overview
- Phase
- Phase 2
- Intervention
- MEDI8852
- Conditions
- Influenza
- Sponsor
- MedImmune LLC
- Primary Endpoint
- Incidence of solicited influenza symptoms, treatment emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events of special interest (TEASIs) - part 1
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of the study is to evaluate the efficacy and safety of MEDI8852 for the treatment of influenza caused by a wild type A/H1N1 challenge strain in healthy, influenza serosusceptible adults.
Detailed Description
The study will be conducted in two parts: Part 1: In Part 1, eight healthy subjects, 18 to 65 years of age, will be enrolled at one study center in the United States of America (USA) and will receive a single intravenous (IV) dose of MEDI8852 (Cohort 1, dose 1) on Day 1. The subjects will be admitted to a Phase 1 unit (Day -1), for dosing (Day 1) and for follow-up (through discharge from the Phase 1 unit on Day 2). Subjects will then be followed through Day 60 for treatment emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), treatment emergent adverse events of special interest (TEAESI), concomitant medications, nasal and blood PK, and ADA. Initiation of Part 2 of the study will be based on review of safety data from Part 1 (Days 1-8) by a study-specific Dose Evaluation Committee (DEC). For subjects in Part 1, the study is approximately 90 days in duration, consisting of a screening period of up to 30 days, a treatment period of 1 day and a follow-up period of 59 days. Part 2: In Part 2, approximately 60 healthy, influenza serosusceptible subjects, 18 to 65 years of age, will be enrolled at the same study center in the USA and will receive a wild-type A/H1N1 challenge strain on Day 1. Subjects will be randomized 1:1:1:1:1 into 5 cohorts (approximately 12 subjects per cohort) to receive the following on Day 2: * Cohort 2: A single IV dose of placebo * Cohort 3: OS, 75 mg orally BID (twice a day) for 5 days * Cohort 4: A single IV low dose of MEDI8852 (dose 2) * Cohort 5: A single IV high dose of MEDI8852 (dose 1) * Cohort 6: A single IV low dose of MEDI8852 (dose 2) and oseltamivir (OS), 75 mg orally BID for 5 days The subjects will be admitted to the Phase 1 unit (Day -1), for influenza challenge strain administration (Day 1), dosing (Day 2 \[Cohorts 2, 4 and 5\] and Days 2-6 \[Cohorts 3 and 6\]), and follow-up (through discharge from the Phase 1 unit on Day 9). Subjects will then be followed through Day 14 for solicited influenza symptoms, and through Day 60 for TEAEs, TESAEs, TEAESIs, concomitant medications, nasal and blood pharmacokinetics (PK), and antidrug antibody (ADA). For subjects in Part 2, the study is approximately 120 days in duration, consisting of a screening period of up to 60 days, a treatment period of 8 days and a follow-up period of 52 days
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 through 65 years at the time of screening.
- •Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act \[HIPAA\] in the USA, European Union \[EU\] Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- •For subjects enrolled in Part 1 and Part 2 of the study, agree to remain restricted to an inpatient unit until released (anticipated to be 3 days and 2 nights for Part 1 and 9 days and 8 nights for Part 2).
- •Able to complete the follow-up period through Day 60 as required by the protocol.
- •Female subjects of childbearing potential must also have a negative urine or blood pregnancy test at screening, on Day -1 and on and Day 1 prior to randomization
- •Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception for at least 2 days prior to the first dose of study drug and must agree to continue using such precautions through Day 60 of the study; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
Exclusion Criteria
- •History of allergic disease or reactions likely to be exacerbated by any component of the study drug, MEDI
- •For subjects enrolled in Part 2 of the study, history of allergic disease or reactions likely to be exacerbated by any component of OS.
- •History of allergic disease or reactions to eggs or egg proteins
- •Any fever ≥ 100.4°F (≥ 38.0°C) regardless of route of measurement and/or respiratory illness (eg, cough or sore throat) within 7 days prior to randomization.
- •Renal impairment that would require modified dosing of OS (ie, estimated creatinine clearance of ≤ 60 mL/min).
- •Any condition that, in the opinion of the investigator, might compromise subject safety or interfere with evaluation of the study drug or interpretation of subject safety or study results.
- •History of Guillain-Barré syndrome.
- •Hemagglutination antibody titer of \>10 for the A/H1N1 challenge strain.
- •Receipt of influenza antiviral therapy within the preceding 14 days.
- •Concurrent participation in another interventional study.
Arms & Interventions
MEDI8852 (dose 1) - part 1
Participants will receive a single intravenous infusion (IV) of MEDI8852 (dose 1)
Intervention: MEDI8852
Placebo - part 2
Participants will received a single IV infusion of placebo ( matched to MEDI8852) on day 2
Intervention: Placebo
Oseltamivir (OS) 75 mg - part 2
Participants will receive 75 mg orally twice a day for 5 days starting at day 2
Intervention: Oseltamivir
MEDI8852 (dose 2) - part 2
Participants will receive a single IV dose of MEDI8852 on day 2 (dose 2)
Intervention: MEDI8852
MEDI8852 (dose 1) - part 2
Participants will receive a single IV infusion of MEDI8852 on day 2 (dose 1)
Intervention: MEDI8852
MEDI8852 (dose 2) +OS 75 mg part 2
Participants will receive a single IV infusion of MEDI8852 (dose 2) on day 2 and 75mg of Oseltamivir twice a day for 5 days starting at day 2
Intervention: Oseltamivir
MEDI8852 (dose 2) +OS 75 mg part 2
Participants will receive a single IV infusion of MEDI8852 (dose 2) on day 2 and 75mg of Oseltamivir twice a day for 5 days starting at day 2
Intervention: MEDI8852
Outcomes
Primary Outcomes
Incidence of solicited influenza symptoms, treatment emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events of special interest (TEASIs) - part 1
Time Frame: Through Day 60
To evaluate the safety and tolerability of MEDI8852 in healthy adults and influenza serosusceptible adults challenged with a wild-type A/H1N1 influenza strain
Quantification of influenza viral shedding (part2) by quantitative real time polymerase chain reaction (qRT-PCR)
Time Frame: On Days 2-9
To evaluate the impact of MEDI8852, either when given alone or in combination with oseltamivir (OS), on nasal shedding of the A/H1N1 challenge strain in healthy, influenza serosusceptible adults, by qRT-PCR
Secondary Outcomes
- Time to resolution of influenza symptoms(Through Day 14)
- Relationship between the influenza viral shedding measured by quantitative real time polymerase chain reaction (qRT-PCR) and administered dose described by a dose-response model(Through Day 9)
- Incidence of solicited influenza symptoms, TEAEs, TESAEs, and TEAESIs(Through Day 14 ( solicited influenza symptoms) and Through Day 60 (TEAEs, TESAEs, and TEAESIs))
- MEDI8852 serum concentration(Through Day 60)
- The incidence of Antidrug Antibody (ADA) to MEDI8852 as summarized by the number and percentage of subjects who are ADA positive by treatment group and time point(Through Day 60)
- MEDI8852 nasal concentration(Through day 60)