A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Motavizumab (MEDI-524) After Dosing for a Second Season in Children
Study Details
Study Description
Brief Summary
The primary objective of this study was to determine the effect on immune reactivity to motavizumab (MEDI-524) of monthly intramuscular (IM) doses of motavizumab (MEDI-524) administered for a second season in children.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This was a Phase 1/2, randomized, double-blind study in which motavizumab (MEDI-524) or palivizumab was administered to children who previously participated in MI-CP104. Children who received at least 3 doses of motavizumab in MI-CP104 were eligible for enrollment. Subjects were randomized 1:1 to receive motavizumab or palivizumab at 15 mg/kg by IM injection every 30 days for a total of 4-5 injections during the 2004-05 RSV season subsequent to the season in which they were participants of MI-CP104. All subjects were evaluated prior to and 30 minutes after each injection of study drug with 2 follow-up evaluations, one at 30 days and the other at 90-120 days after the last dose.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: motavizumab (MEDI-524) 15 mg/kg A single IM injection every 30 days beginning at Day 0 for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
Biological: motavizumab (MEDI-524)
Patients will receive 15 mg/kg MEDI-524 administered IM every 30 days for a total of 4-5 injections.
Other Names:
|
| Active Comparator: palivizumab 15 mg/kg A single IM injection every 30 days beginning at Day 0 for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
Biological: palivizumab 15 mg/kg
Patients will receive 15 mg/kg palivizumab administered IM every 30 days for a total of 4-5 injections.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects Exhibiting Anti-motavizumab Antibodies [Day 0 through 120 days post final dose]
Serum for measurement of anti-motavizumab antibodies was collected prior to the first, second and, if applicable, fifth doses of study drug, and at the 2 follow-up visits 30 and 90-120 days post final dose.
Secondary Outcome Measures
- Number of Subjects Reporting Adverse Events (AEs) [Day 0 through 30 days post final dose]
Assessments of adverse events (including SAEs) were made by clinical investigators according to the protocol.
- Number of Subjects Reporting Serious Adverse Events (SAEs) [Day 0 through 30 days post final dose]
Assessments of SAEs were made by clinical investigators according to the protocol.
- Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations [Day 0 through 30 days post final dose]
Serum chemistry and hematology parameters were measured at baseline, on Days 25-30 and 120, 30 days post the final dose, and at premature discontinuation.
- Motavizumab Serum Concentrations at Each Data Collection Visit [Prior to dosing on Day 0, Day 30, Day 120, and at 30 and 90-120 days post final dose]
Mean serum concentration.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Previous participation in MI-CP104 and received at least 3 injections of MEDI-524 in MI-CP104
-
The child must be less than or equal to 24 months of age at time of entry into the study (child must be entered on or before their 24-month birthday)
-
The child must be able to complete the follow-up visits through 3-4 months after last dose (total length of participation of 6-8 months)
-
Written informed consent obtained from the patient's parent(s) or legal guardian
Exclusion Criteria:
-
Currently hospitalized
-
Receiving chronic oxygen therapy or mechanical ventilation at the time of study entry (including continuous positive airway pressure [CPAP])
-
Evidence of infection with hepatitis A, B, or C virus
-
Known renal impairment, hepatic dysfunction, chronic seizure disorder, or immunodeficiency or HIV infection
-
Suspected serious allergic or immune mediated events with prior receipt of MEDI-524
-
Acute illness or progressive clinical disorder
-
Active infection, including acute respiratory syncytial virus (RSV) infection at the time of enrollment
-
Previous reaction to IGIV, blood products, or other foreign proteins
-
Have ever received palivizumab
-
Received within the past 120 days or currently receiving immunoglobulin products (such as RSV-IGIV [RespiGam(R)], IVIG), or any investigational agents (except MEDI-524)
-
Currently participating in any investigational study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pontificia Universidade Catolica Do Rio Grande | Porto Alegre | Brazil | 90610-000 | |
| 2 | Hospital Das Clinicas Da Faculdade | Ribeirao Preto | Brazil | 14049-900 | |
| 3 | Hospital Clinico De La Pointificia Universidad | Santiago | Chile | ||
| 4 | Hospital Clinico de la Universidad de Chile | Santiago | Chile | ||
| 5 | Hospital Dr. Sotero Del Rio | Santiago | Chile | ||
| 6 | Hospital San Jose | Santiago | Chile |
Sponsors and Collaborators
- MedImmune LLC
Investigators
- Study Director: M Pamela Griffin, M.D., MedImmune LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MI-CP118
Study Results
Participant Flow
| Recruitment Details | Children who received at least 3 doses of motavizumab in Study MI-CP104 during the 2004-2005 RSV season were eligible for enrollment in this study. It was anticipated that approximately 150 children would be enrolled. |
|---|---|
| Pre-assignment Detail | Motavizumab or palivizumab was administered to children, using a 1:1 randomization, at 15 mg/kg of study drug by IM injection every 30 days, for a total of 4-5 doses (determined by when in the RSV season a child was enrolled) during the 2005-2006 RSV season. |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg |
|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Period Title: Overall Study | ||
| STARTED | 66 | 70 |
| COMPLETED | 64 | 67 |
| NOT COMPLETED | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | Total |
|---|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | Total of all reporting groups |
| Overall Participants | 66 | 70 | 136 |
| Age (Months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Months] |
13.25
(3.13)
|
13.59
(2.89)
|
13.43
(3.00)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
23
34.8%
|
32
45.7%
|
55
40.4%
|
| Male |
43
65.2%
|
38
54.3%
|
81
59.6%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Hispanic |
61
92.4%
|
62
88.6%
|
123
90.4%
|
| White/Non-Hispanic |
5
7.6%
|
6
8.6%
|
11
8.1%
|
| Other |
0
0%
|
2
2.9%
|
2
1.5%
|
Outcome Measures
| Title | Number of Subjects Exhibiting Anti-motavizumab Antibodies |
|---|---|
| Description | Serum for measurement of anti-motavizumab antibodies was collected prior to the first, second and, if applicable, fifth doses of study drug, and at the 2 follow-up visits 30 and 90-120 days post final dose. |
| Time Frame | Day 0 through 120 days post final dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received any study drug were included in all summaries of immunogenicity. Day 0 n=66 mota, n=70 pali; Day 25-30 n=65 mota, n=69 pali; Day 120 n=64 mota, n=67 pali; 30 days post final dose n=65 mota, n=67 pali; 90-120 days post final dose n=64 mota, n=67 pali; at any time n=66 mota, n=70 pali. |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg |
|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Measure Participants | 66 | 70 |
| Day 0 |
2
3%
|
3
4.3%
|
| Day 25-30 |
0
0%
|
3
4.3%
|
| Day 120 |
0
0%
|
6
8.6%
|
| 30 Days Post Final Dose |
0
0%
|
9
12.9%
|
| 90-120 Days Post Final Dose |
0
0%
|
10
14.3%
|
| At any time |
2
3%
|
12
17.1%
|
| Title | Number of Subjects Reporting Adverse Events (AEs) |
|---|---|
| Description | Assessments of adverse events (including SAEs) were made by clinical investigators according to the protocol. |
| Time Frame | Day 0 through 30 days post final dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received any study drug were included in all summaries of safety. |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg |
|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Measure Participants | 66 | 70 |
| Number [participants] |
56
84.8%
|
62
88.6%
|
| Title | Number of Subjects Reporting Serious Adverse Events (SAEs) |
|---|---|
| Description | Assessments of SAEs were made by clinical investigators according to the protocol. |
| Time Frame | Day 0 through 30 days post final dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received any study drug were included in all summaries of safety. |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg |
|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Measure Participants | 66 | 70 |
| Number [participants] |
4
6.1%
|
1
1.4%
|
| Title | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations |
|---|---|
| Description | Serum chemistry and hematology parameters were measured at baseline, on Days 25-30 and 120, 30 days post the final dose, and at premature discontinuation. |
| Time Frame | Day 0 through 30 days post final dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received any study drug were included in all summaries of safety. |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg |
|---|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Measure Participants | 66 | 70 |
| ALT Increased |
1
1.5%
|
0
0%
|
| Blood Urea Nitrogen Increased |
0
0%
|
4
5.7%
|
| Anemia |
3
4.5%
|
3
4.3%
|
| Eosinophil Count Increased |
0
0%
|
2
2.9%
|
| Neutropenia |
0
0%
|
2
2.9%
|
| AST increased |
0
0%
|
2
2.9%
|
| Hemoglobin Decreased |
1
1.5%
|
0
0%
|
| Eosinophilia |
3
4.5%
|
4
5.7%
|
| Title | Motavizumab Serum Concentrations at Each Data Collection Visit |
|---|---|
| Description | Mean serum concentration. |
| Time Frame | Prior to dosing on Day 0, Day 30, Day 120, and at 30 and 90-120 days post final dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received any study drug were included in all summaries. Day 0 n= 66; Day 25-30 n=65; Day 120 n=63; 30 days post final dose n=63; 90-120 days post final dose n=62 |
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg |
|---|---|
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. |
| Measure Participants | 66 |
| Day 0 |
1.536
(6.192)
|
| Day 25-30 |
54.59
(16.05)
|
| Day 120 |
86.21
(23.79)
|
| 30 Days Post Final Dose |
76.03
(27.13)
|
| 90-120 Days Post Final Dose |
12.2
(6.260)
|
Adverse Events
| Time Frame | Day 0 through 30 days post final dose. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | ||
| Arm/Group Description | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | ||
All Cause Mortality |
||||
| Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/66 (6.1%) | 1/70 (1.4%) | ||
| Immune system disorders | ||||
| HYPERSENSITIVITY | 1/66 (1.5%) | 1 | 0/70 (0%) | 0 |
| Infections and infestations | ||||
| BRONCHITIS | 1/66 (1.5%) | 1 | 0/70 (0%) | 0 |
| PYELONEPHRITIS | 1/66 (1.5%) | 1 | 0/70 (0%) | 0 |
| RESPIRATORY SYNCYTIAL VIRUS INFECTION | 1/66 (1.5%) | 1 | 0/70 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| PNEUMONITIS CHEMICAL | 1/66 (1.5%) | 1 | 0/70 (0%) | 0 |
| THERMAL BURN | 0/66 (0%) | 0 | 1/70 (1.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 56/66 (84.8%) | 62/70 (88.6%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 3/66 (4.5%) | 3 | 3/70 (4.3%) | 3 |
| EOSINOPHILIA | 3/66 (4.5%) | 3 | 4/70 (5.7%) | 4 |
| Eye disorders | ||||
| CONJUNCTIVITIS | 4/66 (6.1%) | 4 | 4/70 (5.7%) | 4 |
| Gastrointestinal disorders | ||||
| DIARRHOEA | 11/66 (16.7%) | 12 | 10/70 (14.3%) | 13 |
| General disorders | ||||
| INJECTION SITE ERYTHEMA | 10/66 (15.2%) | 16 | 8/70 (11.4%) | 10 |
| PYREXIA | 2/66 (3%) | 2 | 4/70 (5.7%) | 4 |
| Immune system disorders | ||||
| IMMUNISATION REACTION | 2/66 (3%) | 2 | 4/70 (5.7%) | 4 |
| Infections and infestations | ||||
| BRONCHITIS | 21/66 (31.8%) | 33 | 19/70 (27.1%) | 38 |
| CANDIDA NAPPY RASH | 3/66 (4.5%) | 3 | 2/70 (2.9%) | 2 |
| LARYNGITIS | 3/66 (4.5%) | 4 | 4/70 (5.7%) | 4 |
| NASOPHARYNGITIS | 29/66 (43.9%) | 38 | 29/70 (41.4%) | 44 |
| OTITIS MEDIA | 1/66 (1.5%) | 1 | 3/70 (4.3%) | 3 |
| OTITIS MEDIA ACUTE | 4/66 (6.1%) | 5 | 3/70 (4.3%) | 3 |
| PHARYNGITIS | 6/66 (9.1%) | 6 | 8/70 (11.4%) | 10 |
| PNEUMONIA | 2/66 (3%) | 2 | 3/70 (4.3%) | 3 |
| RHINITIS | 6/66 (9.1%) | 6 | 4/70 (5.7%) | 6 |
| TONSILLITIS | 4/66 (6.1%) | 6 | 5/70 (7.1%) | 5 |
| UPPER RESPIRATORY TRACT INFECTION | 3/66 (4.5%) | 3 | 4/70 (5.7%) | 5 |
| VARICELLA | 3/66 (4.5%) | 3 | 0/70 (0%) | 0 |
| Investigations | ||||
| BLOOD UREA INCREASED | 0/66 (0%) | 0 | 4/70 (5.7%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||
| RHINITIS ALLERGIC | 3/66 (4.5%) | 3 | 0/70 (0%) | 0 |
| WHEEZING | 14/66 (21.2%) | 19 | 16/70 (22.9%) | 24 |
| Skin and subcutaneous tissue disorders | ||||
| DERMATITIS ATOPIC | 1/66 (1.5%) | 1 | 3/70 (4.3%) | 3 |
| DERMATITIS DIAPER | 0/66 (0%) | 0 | 5/70 (7.1%) | 5 |
| PRURIGO | 2/66 (3%) | 2 | 4/70 (5.7%) | 4 |
Limitations/Caveats
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.The PIs also agree for data to be presented first as a joint, multi-center publication.
Results Point of Contact
| Name/Title | M. Pamela Griffin, MD/ Clinical Development |
|---|---|
| Organization | MedImmune |
| Phone | 301-398-0000 |
| clinicaltrialenquiries@medimmune.com |
- MI-CP118