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

Respiratory Syncytial Virus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00316264
• Other study ID #: MI-CP127
• Status: Completed
• Phase: Phase 2
• First received: April 18, 2006
• Last updated: November 13, 2012
• Start date: April 2006
• Est. completion date: February 2007

Study information

• Verified date: November 2012
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 24 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Chronic Lung Disease and <= 24 Months of Age or
• Lung Diseases
• Premature With Gestational Age <=35 Weeks and <=6 Months of Age
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

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.
• 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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

Australia,  Chile,  New Zealand, 

References & Publications (1)

Fernández 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 pa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Reporting Serious Adverse Events (SAEs)		Day 0 - Day 150	Yes
Primary	Number of Subjects Reporting Adverse Events (AEs)		Day 0 - Day 150	Yes
Primary	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	Yes
Secondary	The Serum Concentrations of Motavizumab at Day 0		Day 0	No
Secondary	The Trough Serum Concentrations of Motavizumab at Day 60		Day 60	No
Secondary	The Trough Serum Concentrations of Motavizumab at Day 150		Day 150	No
Secondary	The Trough Serum Concentrations of Motavizumab 120-150 Days Post Final Dose		120-150 days post final dose	No
Secondary	The Serum Concentrations of Palivizumab at Day 0		Day 0	No
Secondary	The Trough Serum Concentrations of Palivizumab at Day 60		Day 60	No
Secondary	The Trough Serum Concentrations of Palivizumab at Day 150		Day 150	No
Secondary	The Trough Serum Concentrations of Palivizumab at 120-150 Days Post Final Dose		120-150 days post final dose	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes