Clinical trial NCT00121108: MEDI-524 (Motavizumab) for the Prevention of Respiratory Sycytial Virus (RSV) Disease Among Native American Indian Infants in the Southwestern United States
Official title: A Phase 3 Study of MEDI-524 (Motavizumab), an Enhanced Potency Humanized Respiratory Syncytial Virus (RSV) Monoclonal Antibody, for the Prevention of RSV Disease Among Native American Infants in the Southwestern United States
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Keywords: RSV, infants, Native American Indians
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2005-07-21
Enrollment: 2127
Sex: ALL
Minimum age (years): 0
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American Infants in the Southwestern United States during their first RSV season.

Detailed description: MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American infants during their first RSV season.

Participants were randomized in a 2:1 ratio to receive either 15 mg/kg motavizumab or placebo by intramuscular (IM) injection every 30 days during the RSV season for a maximum of 5 injections.

During their first RSV season, participants were evaluated monthly just prior to each injection of study drug for adverse events (AEs) (including medically attended otitis media), with a final post-dosing follow up evaluation at Study Day 150. During Seasons 1, 2, and 3, blood was to be collected prior to the first and last dose of study drug for serum chemistry evaluations, motavizumab serum concentrations, and anti-motavizumab antibodies. Efficacy and safety outcomes were examined through Study Day 150 and wheezing outcomes were evaluated from the time of randomization until the third birthday.

Eligibility criteria: Inclusion Criteria:

* 6 months of age or younger at randomization (child must be randomized on or before their 6-month birthday)
* Male or female Native American
* General state of good health
* Written informed consent obtained from the participant's parent(s) or legal guardian

Exclusion Criteria:

* Gestational age less than or equal to 35 weeks
* Chronic lung disease of prematurity
* A bleeding diathesis that would preclude IM injections
* Hospitalization at the time of randomization (unless discharge is anticipated within 10 days)
* Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection
* A documented wheezing episode before enrollment
* Known renal impairment
* Known hepatic dysfunction
* Clinically significant congenital anomaly of the respiratory tract
* Chronic seizure or evolving or unstable neurologic disorder
* Congenital heart disease (CHD) (children with uncomplicated CHD \[e.g., Patent ductus arteriosus, small septal defect\] and children with complicated CHD who are currently anatomically and hemodynamically)
* Known immunodeficiency
* Mother with human immunodeficiency virus infection (unless the child has been proven to be not infected)
* Known allergy to Ig products
* Receipt of palivizumab, Respiratory syncytial virus immunoglobulin, intravenous (RSV-IGIV), or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, hepatitis B immunoglobulin, IVIG) within 3 months prior to randomization
* Anticipated use of palivizumab or IVIG during the study (blood transfusions permitted)
* Previous receipt of RSV vaccines
* Participation in other investigational drug product studies
* Any medical or social condition which, in the opinion of the investigator, would adversely affect monitoring the infant
* Inability to complete the study follow-up period through up to 5 years of age

Primary outcomes:
measure: Number of Participants With Respiratory Syncytial Virus (RSV) Hospitalization
timeFrame: From study Day 0 through study Day 150
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From study Day 0 through study Day 150
measure: Number of Participants With RSV Outpatient Medically Attended Lower Respiratory Illness (MA LRI)
timeFrame: From study Day 0 through study Day 150
measure: Number of Participants With Medically Attended-Otitis Media (MA-OM) Events
timeFrame: From study Day 0 through study Day 150
measure: Number of Participants With Frequency of MA-OM Events
timeFrame: From study Day 0 through study Day 150
measure: Number of Participants With Medically Attended Wheezing Episodes
timeFrame: From first year through 3 years
measure: Number of Participants With Serious Early Childhood Wheezing Episodes
timeFrame: From first year through 3 years
measure: Number of Participants With Frequency of Medically Attended Wheezing Events
timeFrame: Study Day 0 through 3 years
measure: Mean Trough Serum Concentrations of Motavizumab
timeFrame: Day 0 (pre Dose 1) and Day 120 (Pre Dose 5)
measure: Number of Participants With Positive Anti-Motavizumab Antibodies After Full Dose
timeFrame: Day 0 (Pre Dose 1) and Day 120 (Pre Dose 5)
measure: Number of Participants With Positive Anti-Motavizumab Antibodies After Any Dose
timeFrame: Day 0 (Pre Dose 1) and Day 120 (Pre Dose 5)
Other outcomes:
Locations:
city: Chinle
country: United States
facility: Research Site
state: Arizona
city: Cibecue
country: United States
facility: Research Site
state: Arizona
city: Fort Definace
country: United States
facility: Research Site
state: Arizona
city: San Carlos
country: United States
facility: Research Site
state: Arizona
city: Tuba City
country: United States
facility: Research Site
state: Arizona
city: Whiteriver
country: United States
facility: Research Site
state: Arizona
city: Winslow
country: United States
facility: Research Site
state: Arizona
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bloomfield
country: United States
facility: Research Site
state: New Mexico
city: Crownpoint
country: United States
facility: Research Site
state: New Mexico
city: Gallup
country: United States
facility: Research Site
state: New Mexico
city: Shiprock
country: United States
facility: Research Site
state: New Mexico
Study officials:
affiliation: MedImmune LLC
name: MedImmune, LLC MedImmune, LLC
role: STUDY_DIRECTOR
References:
citation: O'Brien KL, Chandran A, Weatherholtz R, Jafri HS, Griffin MP, Bellamy T, Millar EV, Jensen KM, Harris BS, Reid R, Moulton LH, Losonsky GA, Karron RA, Santosham M; Respiratory Syncytial Virus (RSV) Prevention study group. Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial. Lancet Infect Dis. 2015 Dec;15(12):1398-408. doi: 10.1016/S1473-3099(15)00247-9. Epub 2015 Nov 4.