Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01475305
Other study ID # CD-ID-MEDI-557-1090
Secondary ID
Status Terminated
Phase Phase 1
First received October 14, 2011
Last updated July 20, 2017
Start date October 20, 2011
Est. completion date December 13, 2012

Study information

Verified date July 2017
Source MedImmune LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 7
Est. completion date December 13, 2012
Est. primary completion date December 3, 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 45 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Placebo
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-557
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.

Locations

Country Name City State
United Kingdom Research Site London

Sponsors (1)

Lead Sponsor Collaborator
MedImmune LLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. From Day 4 to Day 15
Secondary 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. From Day 4 to Day 15
Secondary 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. From Day 5 through Day 31
Secondary 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. From Day 5 through Day 31
Secondary 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. From Day 5 through Day 31
Secondary 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. From Day 5 through Day 31
Secondary 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. From Day 5 through Day 31
Secondary 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]. 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
Secondary Maximum Serum Concentration (Cmax) of MEDI-557 The Cmax is the maximum observed serum concentration of MEDI-557. 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
Secondary Time to Reach Maximum Serum Concentration (Tmax) of MEDI-557 The Tmax is defined as actual sampling time to reach maximum observed MEDI-557 concentration. 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
Secondary Serum Half Life (t1/2) of MEDI-557 Serum decay half-life is the time measured for the serum concentration to decrease by one half. 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
Secondary Area Under the Serum Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557 The AUC(0-t) is the area under the serum concentration-time curve from time zero to any time 't'. 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
Secondary Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of MEDI-557 The AUC (0-infinity) is the area under the serum concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. 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
Secondary Volume of Distribution at Steady-State (Vss) of MEDI-557 Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-infinity])*(AUMC[0-infinity])/AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the serum concentration-time curve from time zero to infinite time. 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
Secondary Mean Clearance of MEDI-557 Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the serum Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]). 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
Secondary Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points MEDI-557 nasal wash concentrations were summarized by each sampling point [LLOQ for MEDI-557 concentration assay was 20.00 nanogram per millilitre (ng/mL) for nasal wash]. Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
Secondary Maximum Nasal Wash Concentration (Cmax) of MEDI-557 The Cmax is the maximum observed nasal wash concentration of MEDI-557. Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
Secondary Time to Reach Maximum Nasal Wash Concentration (Tmax) of MEDI-557 The Tmax is defined as actual sampling time to reach maximum observed MEDI-557 concentration. Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
Secondary Area Under the Nasal Wash Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557 The AUC(0-t) is the area under the nasal wash concentration-time curve from time zero to any time 't'. Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31
Secondary Percentage of Participants With Positive Anti-MEDI-557 Antibodies Anti-drug antibodies in the participants blood sample were detected using a validated immunoassay. Antidrug antibodies to MEDI-557 were defined as a detectable antibody titer with a dilution value of 1:30 or greater. Day 1 (pre-dose); Day 31, 91, 150, 180, 240, 300 and 360 post-dose
Secondary Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 were events between first dose of study drug and Day 360 that were absent before treatment or that worsened relative to pretreatment state. From Day 1 (immediately following administration of study drug) to Day 360
Secondary Number of Participants With Vital Signs Abnormalities Reported as Adverse Events (AEs) Vital signs included temperature, respiration rate, heart rate, blood pressure. Abnormal vital sign parameters included Cardiac Disorders (Bradycardia), Respiratory, Thoracic and Mediastinal Disorders (Tachypnoea, Hyperventilation, Hypopnoea). Participants with abnormalities in these vital Signs investigations recorded as AEs were reported. From Day 1 through Day 31
Secondary Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs) Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs were reported. From Day 1 through Day 91
Secondary Number of Participants With Clinically Meaningful Changes From Baseline in Spirometry Values Spirometry is a standardized assessment to evaluate lung function. Baseline values for spirometry is defined as the last measure prior to viral challenge. Spirometry assessments included percent predicted forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and forced expiratory flow (FEF) 25%-75% values. Days 1, 2, 3 (Baseline), 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 31
See also
  Status Clinical Trial Phase
Active, not recruiting NCT03698084 - RESCEU: Defining the Burden of RSV Disease
Recruiting NCT05550545 - Infant RSV Infections and Health-related Quality of Life of Families
Completed NCT05587478 - A Study of EDP-323 in Healthy Subjects Phase 1
Recruiting NCT06180993 - Evaluation of the Effectiveness and Impact of Nirsevimab Administered as Routine Immunization
Suspended NCT03909867 - Emission Patterns of Respiratory Syncytial Virus
Recruiting NCT06259487 - Coordinated Vaccination Against RSV and Influenza in Patients With Chronic Heart Failure and Its Impact on Prognosis. N/A
Not yet recruiting NCT04144816 - Predictors of Respiratory Syncytial Virus (RSV) Hospitalizations in Infants
Completed NCT01090557 - Exhaled Nitric Oxide in Respiratory Syncytial Virus (RSV) Bronchiolitis: a Pilot Study N/A
Not yet recruiting NCT05928507 - FINDER® Instrument and FINDER® FLU A/B, RSV, SARS-CoV-2 Test Clinical Evaluation Protocol
Completed NCT03062917 - Nasal and Bronchial Absorption Sampling in RSV Bronchiolitis N/A
Completed NCT03691623 - A Phase 2a Study to Evaluate EDP-938 in the Virus Challenge Model Phase 2
Completed NCT03387137 - Evaluating the Infectivity, Safety, and Immunogenicity of a Respiratory Syncytial Virus Vaccine (RSV 6120/∆NS2/1030s) in RSV-Seropositive Children and RSV-Seronegative Infants and Children Phase 1
Completed NCT05070975 - Severity of RSV Infections in Twins
Active, not recruiting NCT04938830 - Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007) Phase 3
Recruiting NCT05568706 - A Study of EDP-938 in Non-hospitalized Adults With RSV Who Are at High Risk for Complications. Phase 2
Completed NCT03755778 - Drug-Drug Interaction Study Between EDP-938, Itraconazole, Rifampin, and Quinidine in Healthy Subjects Phase 1
Completed NCT01483911 - ALX-0171 Phase I Study, Evaluating Single Ascending Dose and Multiple Dose in Healthy Male Volunteers Phase 1
Recruiting NCT06170242 - A Controlled Phase 2a Study to Evaluate the Efficacy of EDP-323 Against Respiratory Syncytial Virus Infection in a Virus Challenge Model Phase 2
Completed NCT03750383 - Drug-Drug Interaction Study Between EDP-938, Cyclosporine and Prednisone in Healthy Adult Subjects Phase 1
Completed NCT05118386 - Safety, Tolerability, and Pharmacokinetics of RSV Monoclonal Antibody RSM01 in Healthy Adults Phase 1