Evaluation of the Safety and Efficacy of a Monoclonal Antibody to Treat Influenza

NCT03903718 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: D6000C00004
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Influenza

Keywords

Influenza; Influenza A; Flu; Flu A

Outcome Measures

Primary Outcomes (2)

• 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

  To evaluate the safety and tolerability of MEDI8852 in healthy adults and influenza serosusceptible adults challenged with a wild-type A/H1N1 influenza strain

  Through Day 60

• Quantification of influenza viral shedding (part2) by quantitative real time polymerase chain reaction (qRT-PCR)

  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

  On Days 2-9

Secondary Outcomes (6)

• 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

Study Arms (6)

MEDI8852 (dose 1) - part 1

EXPERIMENTAL

Participants will receive a single intravenous infusion (IV) of MEDI8852 (dose 1)

Biological: MEDI8852

Placebo - part 2

SHAM COMPARATOR

Participants will received a single IV infusion of placebo ( matched to MEDI8852) on day 2

Drug: Placebo

Oseltamivir (OS) 75 mg - part 2

ACTIVE COMPARATOR

Participants will receive 75 mg orally twice a day for 5 days starting at day 2

Drug: Oseltamivir

MEDI8852 (dose 2) - part 2

EXPERIMENTAL

Participants will receive a single IV dose of MEDI8852 on day 2 (dose 2)

Biological: MEDI8852

MEDI8852 (dose 1) - part 2

EXPERIMENTAL

Participants will receive a single IV infusion of MEDI8852 on day 2 (dose 1)

Biological: MEDI8852

MEDI8852 (dose 2) +OS 75 mg part 2

EXPERIMENTAL

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

Drug: Oseltamivir; Biological: MEDI8852

Interventions

Oseltamivir DRUG

75 mg capsules orally twice a day from Day 2 to Day 7

MEDI8852 (dose 2) +OS 75 mg part 2; Oseltamivir (OS) 75 mg - part 2

MEDI8852 BIOLOGICAL

MEDI8852 is a human IgG1 kappa monoclonal antibody administered as a single IV infusion at either dose 1 or dose 2 on Day 2.

MEDI8852 (dose 1) - part 1; MEDI8852 (dose 1) - part 2; MEDI8852 (dose 2) +OS 75 mg part 2; MEDI8852 (dose 2) - part 2

Placebo DRUG

Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 2.

Placebo - part 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• History of allergic disease or reactions likely to be exacerbated by any component of the study drug, MEDI8852.
• 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.
• Previous receipt of an influenza mAb.
• Previous receipt of immunoglobulin or blood products within 6 months prior to screening.
• History of active infection with hepatitis B or C.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or serum creatinine above 1.1 times the upper limit of normal (ULN) or haemoglobin, white blood cell count, or platelet count below 0.9 times the lower limit of normal at screening.
• Known immunodeficiency due to illness, including human immunodeficiency virus infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening.

Sponsors & Collaborators

• MedImmune LLC: lead

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir; MEDI8852

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be assigned to Part 1 of the study (Cohort 1) in an unblinded manner. Part 2 is a partial double-blind study of MEDI8852 and placebo. Because MEDI8852 and placebo are not completely indistinguishable in appearance, an unblinded investigational product manager will prepare the investigational product using a coloured sleeve to cover the infusion bag containing investigational product. An unblinded investigational product monitor will perform investigational product accountability. The unblinded personnel will not reveal the treatment allocation to the sponsor or site staff. Neither the subject/legal representative nor any of the investigator or sponsor staff who are involved in the treatment or clinical evaluation of the subjects will be aware of the treatment received. In the event that the treatment allocation for a subject becomes known to the investigator or other study staff involved in the management of study subjects, the sponsor must be notified immediately.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: April 4, 2019
• Study Start: April 3, 2020
• Primary Completion: October 9, 2020
• Study Completion: October 9, 2020
• Last Updated: January 18, 2020

Record last verified: 2020-01