Clinical trial NCT01475305: Intranasal Challenge of Healthy Adults With Respiratory Syncytial Virus (RSV)
Official title: A Phase 1 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of MEDI-557 in Healthy Adults Intranasally Challenged With Respiratory Syncytial Virus (RSV)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: RSV Infection
Keywords: Respiratory Syncytial Virus (RSV)
Healthy adults
MEDI-557
Intranasal challenge
Human model
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-11-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Plaque Assay Culture
timeFrame: From Day 4 to Day 15
Secondary outcomes:
measure: 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
timeFrame: From Day 4 to Day 15
measure: Mean Viral Load AUC0-t by Plaque Assay Culture
timeFrame: From Day 5 through Day 31
measure: Mean Viral Load AUC0-t by Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
timeFrame: From Day 5 through Day 31
measure: Mean Nasal RSV Peak as Measured by Plaque Assay Culture
timeFrame: From Day 5 through Day 31
measure: Mean Nasal RSV Peak as Measured by Quantitative Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
timeFrame: From Day 5 through Day 31
measure: Duration of Respiratory Syncytial Virus (RSV) Viral Shedding
timeFrame: From Day 5 through Day 31
measure: Mean Serum MEDI-557 Concentration Through Day 360
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Maximum Serum Concentration (Cmax) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Time to Reach Maximum Serum Concentration (Tmax) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Serum Half Life (t1/2) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Volume of Distribution at Steady-State (Vss) of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Mean Clearance of MEDI-557
timeFrame: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360
measure: Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
timeFrame: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
measure: Maximum Nasal Wash Concentration (Cmax) of MEDI-557
timeFrame: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
measure: Time to Reach Maximum Nasal Wash Concentration (Tmax) of MEDI-557
timeFrame: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
measure: Area Under the Nasal Wash Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557
timeFrame: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
measure: Percentage of Participants With Positive Anti-MEDI-557 Antibodies
timeFrame: Day 1 (pre-dose); Day 31, 91, 150, 180, 240, 300 and 360 post-dose
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Day 1 (immediately following administration of study drug) to Day 360
measure: Number of Participants With Vital Signs Abnormalities Reported as Adverse Events (AEs)
timeFrame: From Day 1 through Day 31
measure: Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
timeFrame: From Day 1 through Day 91
measure: Number of Participants With Clinically Meaningful Changes From Baseline in Spirometry Values
timeFrame: Days 1, 2, 3 (Baseline), 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 31
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Hasan Jafri, MD
role: STUDY_DIRECTOR
References: