Study of Motavizumab (MEDI-524) and Palivizumab Administered Sequentially in the Same Respiratory Syncytial Virus (RSV) Season

A Phase 2, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of Motavizumab (MEDI-524), a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), and Palivizumab When Administered in the Same Season

This is a Phase 2, randomized, double-blind study in which motavizumab (MEDI-524) and palivizumab were administered sequentially to high-risk children during the same respiratory syncytial virus (RSV) season. A control group was administered only motavizumab.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections; Chronic Lung Disease and <= 24 Months of Age or; Premature With Gestational Age <=35 Weeks and <=6 Months of Age
• Intervention / Treatment: Biological: Motavizumab, palivizumab; Biological: Palivizumab, motavizumab; Biological: Motavizumab

Detailed Description

This is a Phase 2, randomized, double-blind study in which motavizumab and palivizumab were administered sequentially to high-risk children during the same RSV season. It was anticipated that approximately 240 children (80 in each group) would be enrolled from the southern hemisphere during the upcoming RSV season (2006). Children were randomized into one of three regimens in a 1:1:1 ratio; the first group received 2 doses of motavizumab followed by 3 doses of palivizumab; the second group received 2 doses of palivizumab followed by 3 doses of motavizumab; and the third group received 5 doses of motavizumab. Motavizumab or palivizumab was administered at 15 mg/kg by IM injection every 30 days, for a total of 5 injections.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Department of Paediatrics and Child Health, The Canberra Hospital
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Neonatalogy John Hunter Hospital
  • Queensland
    • Caboolture, Queensland, Australia, 4510
      • Caboolture Clinical Research
    • Herston, Queensland, Australia, 4029
      • University of Queensland, Royal Children's Hospital
    • Kippa-Ring, Queensland, Australia, 4021
      • Peninsula Clinical Research Centre
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Respiratory Medicine Department, Royal Children's Hospital
• Chile
  • Santiago, Chile
    • Hospital Clinico de la Pontificia Universidad Catolica de Chile
  • Santiago, Chile
    • Hospital Dr. Sotero del Rio
  • Santiago, Chile
    • Hospital Clinico San Borja Arriaran
  • Santiago, Chile
    • Hospital Padre Hurtado
  • Santiago, Chile
    • Hospital Dr Felix Bulnes Cerda
  • Santiago
    • Independencia, Santiago, Chile
      • Hospital Clinico de la Universidad de Chile
    • Independencia, Santiago, Chile
      • Hospital San José
• New Zealand
  • Christchurch, New Zealand
    • Christchurch Women's Hospital
  • Dunedin, New Zealand
    • Paediatric Medicine, Dunedin Hospital
  • Hamilton, New Zealand
    • Department of Paediatrics, Waikato Hospital
  • Palmerston North, New Zealand
    • Child Health, Palmerston North Hospital
  • Auckland
    • Otahuhu, Auckland, New Zealand
      • Kidz First, Middlemore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The child must have been born at less than or equal to 35 weeks gestation and be less than or equal to 6 months of age at the time of entry into the study (child must be entered on or before his/her 6-month birthday); or the child must be less than or equal to 24 months of age at the time of entry into the study (child must be entered on or before his/her 24-month birthday) and diagnosed with chronic lung disease (CLD) of prematurity with stable or decreasing doses of diuretics, steroids, or bronchodilators, or treatment with supplemental oxygen, within the previous 6 months.
• The child must be in general good health at the time of study entry.
• The child's parent(s)/legal guardian must provide written informed consent.
• The child must be able to complete the follow-up visits through 120-150 days from last injection of study drug.
• Parent(s)/legal guardian of patient must have available telephone access.

Exclusion Criteria:

• Hospitalized at the time of study entry (unless discharge is expected within 10 days after entry into the study)
• Receiving chronic oxygen therapy or mechanical ventilation at the time of study entry (including continuous positive airway pressure [CPAP])
• Congenital heart disease (CHD) (children with medically or surgically corrected [closed] patent ductus arteriosus and no other CHD may be enrolled)
• Evidence of infection with hepatitis A, B, or C virus
• Known renal impairment, hepatic dysfunction, chronic seizure disorder, or immunodeficiency or HIV infection (a child of a mother with known HIV infection must be proven to be uninfected at the time of enrollment)
• Suspected serious allergic or immune-mediated events with prior receipt of palivizumab
• Acute illness or progressive clinical disorder
• Active infection, including acute RSV infection, at the time of enrollment
• Previous reaction to intravenous immunoglobulin (IGIV), blood products, or other foreign proteins
• Received within the past 120 days or currently receiving immunoglobulin products (such as RSV-IGIV [RespiGam], IVIG, or palivizumab) or any investigational agents
• Previous participation in a clinical trial of motavizumab
• Currently participating in any investigational study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Motavizumab followed by Palivizumab; 2 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month) followed by 3 doses of palivizumab (15 mg/kg, administered as an intramuscular injection once/month)	Biological: Motavizumab, palivizumab; Motavizumab was provided in sterile vials containing 100 mg of motavizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine-HCl.
Experimental: Palivizumab followed by motavizumab; 2 doses of palivizumab (15 mg/kg, administered as an intramuscular injection once/month) followed by 3 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month)	Biological: Palivizumab, motavizumab; Palivizumab was provided in sterile vials containing 100 mg of palivizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine, and 1.6 mM glycine.
Experimental: Motavizumab control; 5 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month)	Biological: Motavizumab; Motavizumab was provided in sterile vials containing 100 mg of motavizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine-HCl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Serious Adverse Events (SAEs)		Day 0 - Day 150
Number of Subjects Reporting Adverse Events (AEs)		Day 0 - Day 150
Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Serum chemistry samples were collected at Day 0, Day 60, and Day 150. Values representing changes in severity according to the AE grading table were recorded as AEs.	Day 0 - Day 150

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Serum Concentrations of Motavizumab at Day 0		Day 0
The Trough Serum Concentrations of Motavizumab at Day 60		Day 60
The Trough Serum Concentrations of Motavizumab at Day 150		Day 150
The Trough Serum Concentrations of Motavizumab 120-150 Days Post Final Dose		120-150 days post final dose
The Serum Concentrations of Palivizumab at Day 0		Day 0
The Trough Serum Concentrations of Palivizumab at Day 60		Day 60
The Trough Serum Concentrations of Palivizumab at Day 150		Day 150
The Trough Serum Concentrations of Palivizumab at 120-150 Days Post Final Dose		120-150 days post final dose
The Immunogenicity of Motavizumab at Day 0	Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 0
The Immunogenicity of Motavizumab at Day 60	Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 60
The Immunogenicity of Motavizumab at Day 150	Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 150
The Immunogenicity of Motavizumab at 120 to 150 Days Post Final Dose	Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	120 - 150 days post final dose
The Immunogenicity of Motavizumab at Any Time	Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	At any time
The Immunogenicity of Palivizumab at Day 0	Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 0
The Immunogenicity of Palivizumab at Day 60	Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 60
The Immunogenicity of Palivizumab at Day 150	Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	Day 150
The Immunogenicity of Palivizumab at 120 to 150 Days Post Final Dose	Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	120 - 150 days post final pose
The Immunogenicity of Palivizumab at Any Time	Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10.	At any time

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Pamela Griffin, M.D., MedImmune LLC

Publications and helpful links

General Publications

• Fernandez P, Trenholme A, Abarca K, Griffin MP, Hultquist M, Harris B, Losonsky GA; Motavizumab Study Group. A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season. BMC Pediatr. 2010 Jun 3;10:38. doi: 10.1186/1471-2431-10-38.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: April 18, 2006
• First Submitted That Met QC Criteria: April 18, 2006
• First Posted (Estimate): April 20, 2006

Study Record Updates

• Last Update Posted (Estimate): December 11, 2012
• Last Update Submitted That Met QC Criteria: November 13, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: RSV; Respiratory Syncytial Virus; palivizumab; motavizumab; Premature and under 6 mos. of age; Chronic Lung Disease over 6 mos. of age
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Lung Diseases; Respiratory Syncytial Virus Infections; Anti-Infective Agents; Antiviral Agents; Palivizumab
• Other Study ID Numbers: MI-CP127