Intranasal Challenge of Healthy Adults With Respiratory Syncytial Virus (RSV)

Phase 1TerminatedNCT01475305

MedImmune LLC7 enrolled

Overview

The primary objective is to evaluate the suitability of the challenge model in measuring the efficacy of MEDI-557 compared to placebo in healthy adult participants for the reduction in the incidence of RSV through 12 days post-RSV challenge with the RSV Memphis-37 strain.

This is designed to be a double-blind, placebo-controlled, randomized study. Approximately 30 participants will be randomized, dosed and followed. Participants will be randomly assigned to receive a single intravenous (IV) dose of MEDI-557 or placebo. Participants will be inoculated with RSV-A. Participants will be followed for efficacy for 12 days post-RSV challenge. Safety follow-up will be approximately 12 months from randomization.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

Conditions

RSV Infection

Interventions

PlaceboDRUG

Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.

MEDI-557DRUG

Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Healthy as determined by medical history and physical examination. 2. Age 19 through 38 years at the time of screening. 3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. 4. Weight less than or equal to (\<=) 10 kilogram (kg) with body mass index (BMI) less than (\<) 32 kilogram per meter square (kg/m\^2). 5. Normotensive (systolic blood pressure \[BP\] \<150 millimeters of mercury (mmHg) and diastolic BP \< 90 mmHg). 6. Females of childbearing age using contraception. 7. Males who are sexually active with a female partner of childbearing potential, using contraception. 8. Sero-suitable (that is, low serum RSV neutralizing antibody titre) for RSV infection. Exclusion Criteria: Current medical conditions as follows: 1. Clinical evidence of chronic pulmonary disease or any use of a bronchodilator or other asthma medication. 2. Current smoker unwilling/unable to desist for the quarantine phase of the study. 3. History or clinical evidence of recurrent lower respiratory tract infection. 4. Evidence of infection with hepatitis A, B, or C virus or human immunodeficiency virus (HIV) by serology. Medical history as follows: 5. History of immunodeficiency. 6. History of chronic sinusitis. 7. History of frequent epistaxis. 8. History of or current diagnosis of diabetes. 9. Prior/concomitant therapy including * Receipt of any systemic chemotherapeutic agent at any time; * Receipt of systemic glucocorticoids within 1 month, or any other immunosuppressive drug within 6 months prior to challenge. * Receipt of any investigational drug within 6 months prior to dose or concurrent enrolment in another clinical study. * Prior participation in a clinical trial of any experimental RSV viral challenge delivered directly to the respiratory tract at any time, or any other respiratory virus challenge within 1 year prior to dose. 10. Nursing mother. 11. Alcohol or drug addiction/abuse within the past 2 years. 12. A positive urine Class A drug or alcohol screen unless there is a medical reason. 13. History of seasonal hay fever or seasonal allergies. 14. Employees of the clinical study site or sponsor, any other individuals involved with the conduct of the study, or immediate family members of such individuals. 15. Health care workers anticipated to have patient contact within 2 weeks after viral challenge. 16. Participants who, for an additional 2 weeks after discharge from the isolation facility, are likely to have contact with a household member or close contact with someone who is: (a) less than 3 years of age; (b) any person with any known immunodeficiency; (c) any person receiving immunosuppressant medications; (d) any person undergoing or soon to undergo cancer chemotherapy within 28 days of challenge; (e) any person who has diagnosed emphysema or COPD, is elderly residing in a nursing home, or with severe lung disease or medical condition; or (f) any person who has received a transplant (bone marrow or solid organ). 17. As a result of the medical interview, physical examination, or screening investigations, the investigator(s) considers the participant unfit for the study.

Locations (1)

Research Site

London, United Kingdom

Outcomes

Primary Outcomes

Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Plaque Assay Culture

RSV infection is defined as positive plaque assay culture sample for greater than or equal to (\>=) 1 day through 12 days post-RSV challenge. A sample was determined positive if log10 plaque-forming units per milliliter \[pfu/mL\] greater than or equal lower limit of quantitation (LLOQ; 1.69 log10 pfu/mL) and 2 of the 3 replicates must have greater than (\>) 0 pfu/mL.

Time frame: From Day 4 to Day 15

Secondary Outcomes

Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Direct Fluorescent Antibody (DFA), And by Any Method

RSV infection defined as positive quantitative real-time RT-PCR (RSV-A only) sample for \>= 2 consecutive days through 12 days post-RSV challenge. A sample was determined positive if log10 copies/ml \>= limit of quantitation (LLOQ; 2.80 log10 copies/mL). RSV infection defined as positive DFA sample for \>= 2 consecutive days through 12 days post-RSV challenge. RSV infection by any method included positive plaque assay culture sample for \>=1 day through 12 days post-RSV challenge, or positive quantitative real-time RT-PCR (RSV-A only) sample for \>= 2 consecutive days through 12 days post-RSV challenge, or positive DFA sample for \>=2 consecutive days through 12 days post-RSV challenge.

Time frame: From Day 4 to Day 15

Mean Viral Load AUC0-t by Plaque Assay Culture

RSV infection by plaque assay culture defined as positive sample for \>= 1 day through 12 days post-RSV challenge.

Time frame: From Day 5 through Day 31

Mean Viral Load AUC0-t by Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

RSV infection by plaque assay culture defined as positive sample for \>= 2 consecutive days through 12 days post-RSV challenge.

Data from ClinicalTrials.gov

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Time frame: From Day 5 through Day 31

Mean Nasal RSV Peak as Measured by Plaque Assay Culture

RSV infection by plaque assay culture defined as positive sample for \>= 1 day through 12 days post-RSV challenge. log10 pfu/mL = log10 plaque-forming unit per milliliter.

Time frame: From Day 5 through Day 31

Mean Nasal RSV Peak as Measured by Quantitative Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

RSV infection by plaque assay culture defined as positive sample for \>= 2 consecutive days through 12 days post-RSV challenge.

Time frame: From Day 5 through Day 31

Duration of Respiratory Syncytial Virus (RSV) Viral Shedding

Duration of viral shedding defined as the number of days from the first sample positive by any assay (that is, plaque assay culture, quantitative real-time (RT-PCR), or direct fluorescent Antibody (DFA) to the last sample positive by any assay.

Time frame: From Day 5 through Day 31

Mean Serum MEDI-557 Concentration Through Day 360

MEDI-557 serum concentrations were summarized by each sampling point \[LLOQ for MEDI-557 concentration assay was 1.56 microgram per millilitre (μg/mL) for serum\].