Study to Assess the Immune Reactivity of the Liquid and Lyophilized Formulations of Palivizumab (MEDI-493, Synagis) - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment
Condition:	Chronic Lung Disease
Interventions:	Biological: Lyophilized Palivizumab Biological: Liquid Palivizumab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 417 subjects were randomized into the study at 51 sites in the United States between 20 October 2005 and 02 October 2007.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 4 subjects at site #1022 who received all 5 doses of study drug (per drug accountability records) had no further information including case report form that could be obtained. These 4 subjects were excluded from all data analyses.

Reporting Groups

	Description
Liquid Palivizumab	Liquid Palivizumab, 15 mg/kg IM q30 days X 5
Lyophilized Palivizumab	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5

Participant Flow: Overall Study

	Liquid Palivizumab	Lyophilized Palivizumab
STARTED	211	202
COMPLETED	197	190
NOT COMPLETED	14	12
Lost to Follow-up	7	7
Withdrawal by Subject	5	3
Death	0	1
Relocation	0	1
Protocol Violation	1	0
Moved to Dom. Republic	1	0

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Liquid Palivizumab	Liquid Palivizumab, 15 mg/kg IM q30 days X 5
Lyophilized Palivizumab	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5

Baseline Measures

	Liquid Palivizumab	Lyophilized Palivizumab	Total
Number of Participants [units: participants]	211	202	413
Age [units: months] Mean ± Standard Deviation	4.56 ± 4.50	4.00 ± 4.16	4.29 ± 4.34
Gender [units: participants]
Female	104	99	203
Male	107	103	210
Region of Enrollment [units: participants]
United States	211	202	413
Chronic Lung Disease at Prematurity [units: Participants]
Yes	35	26	61
No	176	176	352
Race/Ethnicity [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	1	3	4
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	25	24	49
White	151	149	300
More than one race	0	0	0
Unknown or Not Reported	0	0	0
Hispanic	22	14	36
Other	12	12	24
Gestational Age at Birth [units: Weeks] Mean ± Standard Deviation	32.4 ± 2.7	32.7 ± 2.5	32.5 ± 2.6
Weight at Day 0 [units: Kilogram] Mean ± Standard Deviation	5.326 ± 2.274	5.079 ± 2.264	5.205 ± 2.270

Outcome Measures

1. Primary:

Number and Percentage of Participants With Immune Reactivity [ Day 240-300 follow up ]

Hide Outcome Measure 1

Measure Type	Primary
Measure Title	Number and Percentage of Participants With Immune Reactivity
Measure Description	Presence of anti-palivizumab antibodies
Time Frame	Day 240-300 follow up
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least 2 doses of study drug and had at least 1 blood sample collected (at baseline or Study Day 240-300) were included in the analysis. This included 206 subjects in Arm 1 and 200 subjects in Arm 2. Of these subjects, 191 (Arm 1) and 188 (Arm 2) had adequate blood samples for analysis. This analysis was per protocol.

Reporting Groups

	Description
Liquid Palivizumab	Liquid Palivizumab, 15 mg/kg IM q30 days X 5
Lyophilized Palivizumab	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5
Combined Liquid/Lyophilized Palivizumab	No text entered.

Measured Values

	Liquid Palivizumab	Lyophilized Palivizumab	Combined Liquid/Lyophilized Palivizumab
Number of Participants Analyzed [units: participants]	191	188	379
Number and Percentage of Participants With Immune Reactivity [units: Participants]
Number	0	1	1
Percentage	0.0	0.5	0.3

Statistical Analysis 1 for Number and Percentage of Participants With Immune Reactivity

Groups ^[1]	Liquid Palivizumab
Overall percentage of immune reactivity ^[2]	0.0
95% Confidence Interval	( 0.0 to 1.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of <2-3% based on 95% confidence intervals [(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)].
[2]	Other relevant estimation information:
	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Statistical Analysis 2 for Number and Percentage of Participants With Immune Reactivity

Groups ^[1]	Lyophilized Palivizumab
Overall percentage of immune reactivity ^[2]	0.5
95% Confidence Interval	( 0.0 to 2.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of <2-3% based on 95% confidence intervals [(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)].
[2]	Other relevant estimation information:
	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Statistical Analysis 3 for Number and Percentage of Participants With Immune Reactivity

Groups ^[1]	Combined Liquid/Lyophilized Palivizumab
Overall percentage of immune reactivity ^[2]	0.3
95% Confidence Interval	( 0.0 to 1.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of <2-3% based on 95% confidence intervals [(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)].
[2]	Other relevant estimation information:
	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Only serious adverse events were collected as part of the safety evaluation. One death (asphyxia) occurred in the Lyophilized Palivizumab group; this event was judged not related to study drug.

Results Point of Contact:

Name/Title: Hasan S. Jafri, MD
Organization: MedImmune, LLC
phone: 301-398-0000

No publications provided

Responsible Party:	MedImmune Inc. ( Genevieve Lonosky, M.D. )
Study ID Numbers:	MI-CP116
Study First Received:	October 3, 2005
Results First Received:	October 2, 2008
Last Updated:	March 27, 2009
ClinicalTrials.gov Identifier:	NCT00233064 History of Changes
Health Authority:	United States: Food and Drug Administration