Clinical trial NCT01980966: A Study of MHAA4549A in Healthy Volunteers in an Influenza Challenge Model
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study in Healthy Volunteers to Evaluate the Efficacy and Safety of MHAA4549A in an Influenza Challenge Model
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of MHAA4549A in healthy volunteers in an influenza challenge model. Subjects will be intranasally oculated with the challenge virus and will be randomly assigned to receive a intravenous dose of either MHAA4549A or placebo. In the stage 5 cohort, subjects will be randomly assigned to receive doses of MHAA4549A or placebo or Tamiflu (oseltamivir) orally twice daily for 5 days. All subjects in all cohorts may take Tamiflu twice daily from Day 7 to Day 11.


Eligibility criteria: Inclusion Criteria:

* In good health with no history of major medical conditions from medical history, physical examination and routine laboratory tests
* Male subjects and women of child-bearing potential must use effective contraception as defined by protocol, starting at entry to quarantine and continuing until Day 120 follow-up visit
* Sero-suitable for challenge virus

Exclusion Criteria:

* Women who have been pregnant within 6 months prior to the study, or who have been breastfeeding within 3 months prior to the study, or who have a positive pregnancy test at any point in the study
* Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease or malignancy, as judged by the CI
* Abnormal pulmonary function evidenced by clinically significant abnormalities in spirometry
* History of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung disease of any etiology. A history of childhood asthma before the age of 12 is acceptable provided the subject is asymptomatic without treatment.
* History suggestive of respiratory infection within 14 days prior to admission to the unit

Primary outcomes:
measure: Viral area under the concentration-time curve (AUC) of nasopharyngeal viral load by quantitative Polymerase Chain Reaction (qPCR)
timeFrame: 8 days
Secondary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: 120 days
measure: Safety: Change in lung function
timeFrame: from pre-challenge to Day 29
measure: Safety: Incidence of anti-therapeutic antibodies (ATAs)
timeFrame: 120 days
measure: Pharmacokinetics: Area under the concentration-time curve
timeFrame: 8 days
measure: AUC of nasopharyngeal viral load, as measured by cell culture
timeFrame: 8 days
measure: Peak viral load (qPCR and cell culture)
timeFrame: 8 days
measure: Duration of viral shedding
timeFrame: 8 days
measure: Duration of Grade 2 or worse symptoms (from first occurrence of any Grade >2 symptom to last occurrence of any Grade >2 symptom)
timeFrame: 8 days
measure: Peak/AUC of composite symptoms
timeFrame: 8 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Retroscreen Ltd
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: McBride JM, Lim JJ, Burgess T, Deng R, Derby MA, Maia M, Horn P, Siddiqui O, Sheinson D, Chen-Harris H, Newton EM, Fillos D, Nazzal D, Rosenberger CM, Ohlson MB, Lambkin-Williams R, Fathi H, Harris JM, Tavel JA. Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01154-17. doi: 10.1128/AAC.01154-17. Print 2017 Nov.
citation: Deng R, Lee AP, Maia M, Lim JJ, Burgess T, Horn P, Derby MA, Newton E, Tavel JA, Hanley WD. Pharmacokinetics of MHAA4549A, an Anti-Influenza A Monoclonal Antibody, in Healthy Subjects Challenged with Influenza A Virus in a Phase IIa Randomized Trial. Clin Pharmacokinet. 2018 Mar;57(3):367-377. doi: 10.1007/s40262-017-0564-y.