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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00316264

Enrollment

260

Registered

2006-04-20

Start date

2006-04-30

Completion date

2007-02-28

Last updated

2012-12-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

Keywords

Respiratory Syncytial Virus, Premature and under 6 mos. of age, Chronic Lung Disease over 6 mos. of age, palivizumab, motavizumab, RSV

Brief 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.

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.

Interventions

BIOLOGICALMotavizumab, 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.

BIOLOGICALPalivizumab, 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.

BIOLOGICALMotavizumab

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

No minimum to 24 Months

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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.	Day 0 - Day 150	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.

Secondary

Measure	Time frame	Description
The Immunogenicity of Palivizumab at Day 60	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.
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	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.
The Serum Concentrations of Motavizumab at Day 0	Day 0	—
The Immunogenicity of Motavizumab at Day 150	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.
The Immunogenicity of Motavizumab at 120 to 150 Days Post Final Dose	120 - 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.
The Immunogenicity of Motavizumab at Any Time	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.
The Immunogenicity of Palivizumab at Day 0	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.
The Immunogenicity of Palivizumab at Day 150	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.
The Immunogenicity of Palivizumab at 120 to 150 Days Post Final Dose	120 - 150 days post final pose	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.
The Immunogenicity of Palivizumab at Any Time	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.
The Immunogenicity of Motavizumab at Day 60	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.
The Trough Serum Concentrations of Motavizumab at Day 60	Day 60	—
The Trough Serum Concentrations of Motavizumab at Day 150	Day 150	—

Countries

Australia, Chile, New Zealand

Participant flow

Recruitment details

It was anticipated that approximately 240 children (80 in each group) would be enrolled from the southern hemisphere during the upcoming RSV season (2006).

Pre-assignment details

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.

Participants by arm

Arm	Count
Motavizumab (MEDI-524) 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)	83
Palivizumab Followed by Motavizumab (MEDI-524) 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)	84
Motavizumab (MEDI-524) Control 5 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month)	93
Total	260

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	2	0	0
Overall Study	Lost to Follow-up	0	1	0
Overall Study	Other	1	1	0
Overall Study	Withdrawal of Consent	3	5	6

Baseline characteristics

Characteristic	Motavizumab (MEDI-524) Followed by Palivizumab	Palivizumab Followed by Motavizumab (MEDI-524)	Motavizumab (MEDI-524) Control	Total
Age Continuous	3.68 months STANDARD_DEVIATION 3.13	3.35 months STANDARD_DEVIATION 2.25	3.92 months STANDARD_DEVIATION 2.43	3.66 months STANDARD_DEVIATION 2.62
Sex: Female, Male Female	32 Participants	41 Participants	45 Participants	118 Participants
Sex: Female, Male Male	51 Participants	43 Participants	48 Participants	142 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	75 / 83	74 / 83	83 / 93
serious Total, serious adverse events	19 / 83	7 / 83	11 / 93

Outcome results

Primary

Number of Subjects Reporting Adverse Events (AEs)

Time frame: Day 0 - Day 150

Population: The safety population included all randomized subjects who received study drug and had any safety follow-up.

Arm	Measure	Value (NUMBER)
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects Reporting Adverse Events (AEs)	77 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects Reporting Adverse Events (AEs)	75 participants
Motavizumab (MEDI-524) Control	Number of Subjects Reporting Adverse Events (AEs)	83 participants

Primary

Number of Subjects Reporting Serious Adverse Events (SAEs)

Time frame: Day 0 - Day 150

Population: The safety population included all randomized subjects who received study drug and had any safety follow-up.

Arm	Measure	Value (NUMBER)
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects Reporting Serious Adverse Events (SAEs)	19 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects Reporting Serious Adverse Events (SAEs)	7 participants
Motavizumab (MEDI-524) Control	Number of Subjects Reporting Serious Adverse Events (SAEs)	11 participants

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.

Time frame: Day 0 - Day 150

Population: The safety population included all randomized subjects who received study drug and had any safety follow-up.

Arm	Measure	Group	Value (NUMBER)
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Blood urea increased	1 participants
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Liver function test abnormal	0 participants
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Alanine aminotransferase increased	1 participants
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Hepatic enzyme increased	1 participants
Motavizumab (MEDI-524) Followed by Palivizumab	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Aspartate aminotransferase increased	2 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Liver function test abnormal	0 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Alanine aminotransferase increased	1 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Hepatic enzyme increased	0 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Blood urea increased	1 participants
Palivizumab Followed by Motavizumab (MEDI-524)	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Aspartate aminotransferase increased	3 participants
Motavizumab (MEDI-524) Control	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Aspartate aminotransferase increased	2 participants
Motavizumab (MEDI-524) Control	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Blood urea increased	3 participants
Motavizumab (MEDI-524) Control	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Alanine aminotransferase increased	5 participants
Motavizumab (MEDI-524) Control	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Liver function test abnormal	1 participants
Motavizumab (MEDI-524) Control	Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs.	Hepatic enzyme increased	0 participants

Secondary