A Phase 2a to Evaluate the Safety of MEDI8852 in Adults With Uncomplicated Influenza (MEDI8852)

• ClinicalTrials.gov Identifier: NCT02603952
• Recruitment Status: Completed
• First Posted: November 13, 2015
• Results First Posted: June 8, 2018
• Last Update Posted: June 8, 2018
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: November 2, 2015
• First Posted Date: November 13, 2015
• Results First Submitted Date: February 15, 2018
• Results First Posted Date: June 8, 2018
• Last Update Posted Date: June 8, 2018
• Actual Study Start Date: December 7, 2015
• Actual Primary Completion Date: December 9, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2018)

• Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10 [ Time Frame: Day 1 (post-dose) through Day 10 ]
  Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
• Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13 [ Time Frame: Day 10 through Day 13 ]
  Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (post-dose) through Day 28 ]
  An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 28 that were absent before treatment or that worsened relative to pre-treatment state.
• Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 (post-dose) through Day 101 ]
  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 experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre-treatment state.
• Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs) [ Time Frame: Day 1 (post-dose) through Day 101 ]
  An AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. An AESI was one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre treatment state.

Original Primary Outcome Measures (submitted: November 10, 2015)

• The occurence of Adverse Events [ Time Frame: Through Day 28 ]
  Occurence of adverse events.
• The occurence of Serious Adverse Events [ Time Frame: Through Study Day 101 ]
  Occurence of serious adverse events.
• Solicited Influenza Symptoms [ Time Frame: Through Day 10 ]
  Occurence of solicited influenza sypmtoms.
• The occurence of Adverse Events of Special Interest (AESIs) [ Time Frame: Through Day 101 ]
  Occurence of Adverse Events of Special Interest.

Current Secondary Outcome Measures (submitted: May 7, 2018)

• Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) [ Time Frame: Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13 ]
  Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure influenza viral shedding from the nasopharyngeal swabs. Percentage of participants who shed influenza virus are reported.
• Quantitation of Influenza Viral Shedding as Measured by qRT-PCR [ Time Frame: Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13 ]
  qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.
• Number of Days of Influenza Viral Shedding as Measured by qRT-PCR [ Time Frame: From Baseline (Day 1) to Day 7; and Day 9 to Day 13 ]
  Number of days of viral shedding for participants who shed influenza virus is reported. qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.
• Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site [ Time Frame: From Baseline (Day 1) to Day 13 ]
  Genotypic analysis was performed to identify all amino acid changes in MEDI8852 binding site between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with changes in the amino acid corresponding to MEDI8852 binding site is reported. Due to the fact that the percentage of participants with amino acid changes in MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed.
• Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay [ Time Frame: From Baseline (Day 1) to Day 13 ]
  Viral susceptibility to MEDI8852 was measured by a Madin-Darby canine kidney (MDCK) cell-based microneutralization assay (Virospot) for viruses recovered from baseline samples and viruses recovered from samples following treatment that contain amino acid changes within the MEDI8852 binding site. Participants with detectable levels (50% tissue culture infectious dose [TCID50]) of virus were considered susceptible and were reported. Due to the fact that the number of participants with viral susceptibility to MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed.
• Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations [ Time Frame: From Baseline (Day 1) to Day 13 ]
  Genotypic analysis was performed to identify all amino acid changes in neuraminidase (NA) gene between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with virus containing known oseltamivir resistance-associated mutations (change in the NA genes) is reported. Due to the fact that the percentage of participants with virus containing known oseltamivir resistance-associated mutation was zero across all participant samples analyzed, no additional per arm analyses were performed.

Original Secondary Outcome Measures (submitted: November 10, 2015)

• Quantification of influenza viral shedding by qRT-PCR. [ Time Frame: Through Study Day 7 ]
  Evaluation of occurence of influenza viral shedding at baseline (Day 1), Day 3, 5, and 7.
• To evaluate the proportion of subjects with resistance to oseltamivir. [ Time Frame: Baseline through Day 7 ]
  Evaluate Oseltamivir resistance-associated mutations at baseline (Day 1) and following treatments.
• To evaluate viral resistance to MEDI8852 through genotypic analysis. [ Time Frame: Baseline through Day 7 ]
  Evaluate genotypic analysis of virus to MEDI8852 at baseline (Day 1) and following treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2a to Evaluate the Safety of MEDI8852 in Adults With Uncomplicated Influenza
• Official Title: A Phase 2a, Randomized, Partial Double-blind, Single Dose, Active-controlled, Dose Ranging Study to Evaluate the Safety of MEDI8852 in Adults With Acute, Uncomplicated Influenza
• Brief Summary: The purpose of this study is to evaluate safety and tolerability of a single dose of MEDI8852 when given with oseltamivir, the safety and tolerability of oseltamivir alone, and the safety and tolerability of a single dose of MEDI8852 alone in adult participants with acute, uncomplicated influenza caused by Type A strains.
• Detailed Description: The MEDI8852 phase 2a study will evaluate the safety and tolerability of a single intravenous (IV) dose of MEDI8852 administered in conjunction with oseltamivir, the safety and tolerability of oseltamivir alone and the safety and tolerability of a single IV dose of MEDI8852 alone in adult participants with confirmed acute, uncomplicated influenza caused by Type A strains. Enrollment is planned in the United States, South Africa, and Australia.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Influenza

Intervention

• Drug: Oseltamivir
  75 mg capsules orally BID from Day 1 to Day 5.
• Drug: MEDI8852
  MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.
• Drug: Placebo
  Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.

Study Arms

• Placebo Comparator: Placebo + Oseltamivir 75 mg
  Participants will receive a single intravenous (IV) infusion of placebo (matched to MEDI8852) on Day 1 and oseltamivir 75 milligrams (mg) capsules orally twice a day (BID) from Day 1 to Day 5.
  Interventions:

  • Drug: Oseltamivir
  • Drug: Placebo
• Experimental: MEDI8852 750 mg + Oseltamivir 75 mg
  Participants will receive a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.
  Interventions:

  • Drug: Oseltamivir
  • Drug: MEDI8852
• Experimental: MEDI8852 3000 mg + Oseltamivir 75 mg
  Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.
  Interventions:

  • Drug: Oseltamivir
  • Drug: MEDI8852
• Experimental: MEDI8852 3000 mg
  Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1.
  Intervention: Drug: MEDI8852

• Publications *: Ali SO, Takas T, Nyborg A, Shoemaker K, Kallewaard NL, Chiong R, Dubovsky F, Mallory RM. Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00694-18. doi: 10.1128/AAC.00694-18. Print 2018 Nov.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2018): 126
• Original Estimated Enrollment (submitted: November 10, 2015): 160
• Actual Study Completion Date: December 9, 2016
• Actual Primary Completion Date: December 9, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 18 through 65 years at the time of screening.
• Symptomatic presumptive Influenza A infection with onset of symptoms less than or equal to (≤) 5 days prior to MEDI8852 administration and defined as the presence of:
• Fever of greater than or equal to (≥) 38.0 degrees Celsius (100.4 degrees Fahrenheit) at screening AND
• ≥ 1 moderate systemic symptom (headache, malaise, myalgia, sweats and/or chills, or fatigue) AND
• ≥ 1 moderate respiratory symptom (cough, sore throat, or nasal symptoms)
• Influenza A infection confirmed with positive rapid antigen test
• Able to complete the follow-up period through Day 101 as required by protocol (including telephone follow-up for Days 11 to 101)
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for at least 2 days prior to the first dose of investigational product and must agree to continue using such precautions through Day 101 of the study

Exclusion Criteria:

• Hospitalized subjects.
• Receipt of influenza antiviral therapy within the preceding 14 days.
• Receipt of immunoglobulin or blood products within 6 months prior to screening.
• Known immunodeficiency due to illness, including human immunodeficiency virus (HIV), 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.
• Current clinical evidence of pneumonia.
• Active bacterial infection requiring treatment with oral or parenteral antibiotics.
• History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 3 years.
• Any planned surgical procedure before completion of Day 101.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: South Africa, United States

Administrative Information

• NCT Number: NCT02603952
• Other Study ID Numbers: D6000C00002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedImmune LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: MedImmune LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: MedImmune LLC
• Verification Date: May 2018