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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00233064
• Collaborator: (none)
• Enrollment: 417
• Locations: 54
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the rate of anti-palivizumab antibodies (also referred to as immune reactivity or immunogenicity) in subjects receiving either the liquid or lyophilized formulation of palivizumab. This study will compare the number and percentage of subjects with anti-palivizumab antibodies receiving either the liquid or lyophilized formulation of palivizumab.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lung Disease	Biological: Lyophilized Palivizumab; Biological: Liquid Palivizumab	Phase 4

Detailed Description

The approved liquid formulation of palivizumab was developed to simplify preparation of the drug before injection. Both formulations of palivizumab have been shown to be bioequivalent in children 6 months of age or younger with a history of chronic lung disease. In previous studies of liquid palivizumab, immunogenicity was evaluated up to 2 months after dosing in adults, and 1 month after dosing in children. In this study, MI-CP116, immunogenicity will be evaluated between 4 and 6 months after the last dose of study drug, in order to provide data at a time point significantly distant from dosing when drug interference is minimal.

Study Design

• Study Type: Interventional
• Actual Enrollment: 417 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Randomized, Double-Blind Study to Assess the Immune Reactivity of the Liquid and Lyophilized Formulations of Palivizumab (MEDI-493, Synagis) in Children at High Risk for the Development of Serious RSV Disease
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Liquid Palivizumab	Biological: Liquid Palivizumab; Patients will receive 15 mg/kg of liquid palivizumab administered intramuscularly every 30 days for a total of 5 injections.; Other Names: Synagis
Active Comparator: 2 Lyophilized Palivizumab	Biological: Lyophilized Palivizumab; Patients will receive 15 mg/kg of lyophilized palivizumab administered intramuscularly every 30 days for a total of 5 injections.; Other Names: Synagis

Outcome Measures

Primary Outcome Measures

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

   Presence of anti-palivizumab antibodies

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 24 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Medically stable child with chronic lung disease of prematurity who is ≤24 months of age at randomization OR child with premature birth (gestational age ≤35 weeks or less) and who is 6 months of age or younger at randomization

• Written informed consent obtained from the patient's parent(s) or legal guardian(s)

• The child must be able to complete the follow-up visit 4-6 months after the last dose of study drug

Exclusion Criteria:

• Hospitalization at the time of randomization (unless discharge is anticipated within 3 weeks)

• Be receiving mechanical ventilation at the time of study entry (including CPAP)

• Congenital heart disease (children with uncomplicated CHD [e.g., PDA, small septal defect] and children with complicated CHD who are currently anatomically and hemodynamically normal can be enrolled).

• Mother with HIV infection (unless the child has been proven to be not infected)

• Life expectancy <6 months

• Known allergy to Ig products

• Acute respiratory or other acute infection or illness

• Previous reaction to IGIV, blood products, or other foreign proteins

• Receipt of lyophilized palivizumab, RSV-IG IV, or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, Hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization

• Any previous receipt of MEDI-524

• Participation in other investigational drug product studies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Pediatric Associates	Birmingham	Alabama	United States	35235
2	Clinical Research Consultants	Hoover	Alabama	United States	35216
3	The University of Alabama School of Medicine	Tuscaloosa	Alabama	United States	35487
4	All for Kids Pediatric Clinic	Little Rock	Arkansas	United States	72211
5	Family Medical Center	Foothill Ranch	California	United States	92610
6	Edinger Medical Group	Fountain Valley	California	United States	92708
7	Doctors Medical Group	West Covina	California	United States	91790
8	Convenience Care	West Covina	California	United States	91791
9	Norwich Pediatric Group, P.C.	Norwich	Connecticut	United States	06360
10	The Allergy Center at Brookstone	Columbus	Georgia	United States	31904
11	Physicians to Children and Adolescents	Bardstown	Kentucky	United States	40004
12	Peak Medical Research LLC	Owensboro	Kentucky	United States	42303
13	Boston University Medical Center	Boston	Massachusetts	United States	02118
14	Pediatric Association of Fall River	Fall River	Massachusetts	United States	02724
15	Woburn Pediatric Associates	Woburn	Massachusetts	United States	01801
16	Michigan Institute of Medicine	Livonia	Michigan	United States	41852
17	Meridian Clinical Research	Omaha	Nebraska	United States	68134
18	St. Joseph's Childrens Hospital	Paterson	New Jersey	United States	07503
19	Maimonides Pediatric Pulmonology	Brooklyn	New York	United States	11230
20	North Carolina Children's & Adult's Clinical Research Foundation/Purcell Clinic	Laurinburg	North Carolina	United States	28352
21	Capitol Pediatric And Adolescent Center	Raleigh	North Carolina	United States	27609
22	North Carolina Children's and Adult's Clinical Research Foundation	Sylva	North Carolina	United States	28779
23	Medcenter One/Q&R Clinic	Bismarck	North Dakota	United States	58501
24	Dakota Clinic, Ltd. / Innvois Health	Fargo	North Dakota	United States	58103
25	Trinity Medical Group-Health Center Medical Arts	Minot	North Dakota	United States	58701
26	Dr. Shelly David Senders, M.D., Inc.	Cleveland	Ohio	United States	44118
27	Northeast Cincinnati Pediatric Associates, Inc	Mason	Ohio	United States	45040
28	Santiago Reyes, M.D.	Oklahoma City	Oklahoma	United States	73112
29	Tri-State Pediatrics	Beaver Falls	Pennsylvania	United States	15010
30	Greenville Medical Center	Greenville	Pennsylvania	United States	16125
31	CCP - Armstrong Pediatrics	Kittanning	Pennsylvania	United States	16201
32	Pediatric Alliance of Latrobe	Latrobe	Pennsylvania	United States	15650
33	Temple Univ. Children's Medical Center	Philadelphia	Pennsylvania	United States	19140
34	Pediatric Alliance, Southwestern	Pittsburgh	Pennsylvania	United States	15217
35	South Hills Pediatrics	Pittsburgh	Pennsylvania	United States	15227
36	Pediatric Alliance, Southwestern	Pittsburgh	Pennsylvania	United States	15236
37	Primary Physician's Research, Inc.	Pittsburgh	Pennsylvania	United States	15241
38	Laurel Pediatrics	Uniontown	Pennsylvania	United States	15401
39	Brown Clinic P.L.L.P./Northridge Clinic	Watertown	South Dakota	United States	57201
40	Jackson Clinic	Jackson	Tennessee	United States	38305
41	Holston Medical Group; Pediatrics at Meadowview Lane	Kingsport	Tennessee	United States	37660
42	Holston Medical Group; Pediatrics at Stone Plaza	Kingsport	Tennessee	United States	37660
43	Sadler Clinic	Conroe	Texas	United States	77304
44	Pediatric Allergy/Immunology Associates, PA	Dallas	Texas	United States	75230
45	MedPro Research	Houston	Texas	United States	77004
46	Pediatric Associates	Houston	Texas	United States	77087
47	Quality Assurance Research Center	San Antonio	Texas	United States	78205
48	Wee Care Pediatrics	Layton	Utah	United States	84041
49	Bear Care Pediatrics	Ogden	Utah	United States	84405
50	Utah Valley Pediatrics	Provo	Utah	United States	84604
51	Families First Pediatrics	South Jordan	Utah	United States	84095
52	Advanced Pediatrics	Vienna	Virginia	United States	22180
53	WVU Department of Pediatrics	Charleston	West Virginia	United States	25202
54	Monroe Clinic	Monroe	Wisconsin	United States	53566

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: Genny Losonsky, MD, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

• Makari D, Jensen KM, Harris B, Jafri HS. Randomized, Double-Blind Study of the Safety of the Liquid Versus Lyophilized Formulation of Palivizumab in Premature Infants and Children with Chronic Lung Disease of Prematurity. Infect Dis Ther. 2014 Dec;3(2):339-47. doi: 10.1007/s40121-014-0033-y. Epub 2014 Aug 26.

• ClinicalTrials.gov Identifier: NCT00233064
• Other Study ID Numbers: MI-CP116
• First Posted: Oct 5, 2005
• Last Update Posted: Jun 27, 2018
• Last Verified: Jan 1, 2010

• Additional relevant MeSH terms: Lung Diseases; Palivizumab

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	Liquid Palivizumab	Lyophilized Palivizumab
Arm/Group Description	Liquid Palivizumab, 15 mg/kg IM q30 days X 5	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5
Period Title: Overall Study
STARTED	211	202
COMPLETED	197	190
NOT COMPLETED	14	12

Baseline Characteristics

Arm/Group Title	Liquid Palivizumab	Lyophilized Palivizumab	Total
Arm/Group Description	Liquid Palivizumab, 15 mg/kg IM q30 days X 5	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5	Total of all reporting groups
Overall Participants	211	202	413
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	4.56 (4.50)	4.00 (4.16)	4.29 (4.34)
Sex: Female, Male (Count of Participants)
Female	104 49.3%	99 49%	203 49.2%
Male	107 50.7%	103 51%	210 50.8%
Region of Enrollment (participants) [Number]
United States	211 100%	202 100%	413 100%
Chronic Lung Disease at Prematurity (Number) [Number]
Yes	35 16.6%	26 12.9%	61 14.8%
No	176 83.4%	176 87.1%	352 85.2%
Race/Ethnicity (Number) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.5%	3 1.5%	4 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	25 11.8%	24 11.9%	49 11.9%
White	151 71.6%	149 73.8%	300 72.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Hispanic	22 10.4%	14 6.9%	36 8.7%
Other	12 5.7%	12 5.9%	24 5.8%
Gestational Age at Birth (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	32.4 (2.7)	32.7 (2.5)	32.5 (2.6)
Weight at Day 0 (Kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilogram]	5.326 (2.274)	5.079 (2.264)	5.205 (2.270)

Outcome Measures

1. Primary Outcome

Title	Number and Percentage of Participants With Immune Reactivity
Description	Presence of anti-palivizumab antibodies
Time Frame	Day 240-300 follow up

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liquid Palivizumab	Lyophilized Palivizumab	Combined Liquid/Lyophilized Palivizumab
Arm/Group Description	Liquid Palivizumab, 15 mg/kg IM q30 days X 5	Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5
Measure Participants	191	188	379
Number	0 0%	1 0.5%	1 0.2%
Percentage	0.0 0%	0.5 0.2%	0.3 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liquid Palivizumab
	Comments	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)].
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Overall percentage of immune reactivity
	Estimated Value	0.0
	Confidence Interval	() 95%; 0.0 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lyophilized Palivizumab
	Comments	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)].
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Overall percentage of immune reactivity
	Estimated Value	0.5
	Confidence Interval	() 95%; 0.0 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combined Liquid/Lyophilized Palivizumab
	Comments	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)].
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Overall percentage of immune reactivity
	Estimated Value	0.3
	Confidence Interval	() 95%; 0.0 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The number and percentage of subjects with immune reactivity at Study Day 240-300 were constructed using the Clopper-Pearson Method.

Adverse Events

Time Frame	Serious adverse events were collected from the time of the first study drug administration through Study Day 150. Adverse events were not collected in this study.
Arm/Group Title	Liquid Palivizumab		Lyophilized Palivizumab
Arm/Group Description	Liquid Palivizumab, 15 mg/kg IM q30 days X 5		Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5
All Cause Mortality
	Liquid Palivizumab		Lyophilized Palivizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Liquid Palivizumab		Lyophilized Palivizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/211 (8.5%)		12/202 (5.9%)
Blood and lymphatic system disorders
Lymphadenitis	1/211 (0.5%)	1	0/202 (0%)	0
Congenital, familial and genetic disorders
Cleft Lip	1/211 (0.5%)	1	1/202 (0.5%)	1
Gastrointestinal disorders
Anal Fissure	1/211 (0.5%)	1	0/202 (0%)	0
Gastroesophageal Reflux Disease	1/211 (0.5%)	1	0/202 (0%)	0
Inguinal Hernia	1/211 (0.5%)	1	1/202 (0.5%)	1
Umbilical Hernia	1/211 (0.5%)	1	0/202 (0%)	0
Occult Blood Positive	0/211 (0%)	0	1/202 (0.5%)	1
Infections and infestations
Abscess	0/211 (0%)	0	1/202 (0.5%)	1
Bronchiolitis	6/211 (2.8%)	6	3/202 (1.5%)	3
Bronchopneumonia	1/211 (0.5%)	1	0/202 (0%)	0
Cellulitis	1/211 (0.5%)	1	0/202 (0%)	0
Infectious Croup	1/211 (0.5%)	1	0/202 (0%)	0
Gastroenteritis	2/211 (0.9%)	2	2/202 (1%)	2
Gastroenteritis Rotavirus	1/211 (0.5%)	1	0/202 (0%)	0
Viral Infection	2/211 (0.9%)	2	0/202 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/211 (0.5%)	1	0/202 (0%)	0
Failure to Thrive	0/211 (0%)	0	1/202 (0.5%)	1
Musculoskeletal and connective tissue disorders
Craniosynostosis	1/211 (0.5%)	1	0/202 (0%)	0
Nervous system disorders
Complex Partial Seizures	1/211 (0.5%)	1	0/202 (0%)	0
Convulsions	1/211 (0.5%)	1	0/202 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/211 (0.5%)	1	0/202 (0%)	0
Respiratory, thoracic and mediastinal disorders
Apnoea	0/211 (0%)	0	1/202 (0.5%)	1
Asphyxia	0/211 (0%)	0	1/202 (0.5%)	1
Dyspnoea	0/211 (0%)	0	1/202 (0.5%)	1
Respiratory Distress	0/211 (0%)	0	2/202 (1%)	2
Other (Not Including Serious) Adverse Events
	Liquid Palivizumab		Lyophilized Palivizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/211 (0%)		0/202 (0%)

Limitations/Caveats

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.

More Information

Certain Agreements

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

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.