Safety Study of a Monoclonal Antibody to Respiratory Syncytial Virus (RSV) in Children Hospitalized With RSV Infection

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00192504
• Collaborator: (none)
• Enrollment: 31
• Arms: 4
• Duration (Months): 10.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety of motavizumab (MEDI-524) following a single intravenous dose in children hospitalized with respiratory syncytial virus (RSV).

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Prophylaxis	Biological: Motavizumab; Biological: Motavizumab; Biological: Motavizumab; Other: Placebo	Phase 1

Detailed Description

This study was designed as a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation, multicenter clinical study to evaluate the safety, tolerability, serum concentrations, and immunogenicity of a single intravenous dose of motavizumab (MEDI-524) and the effect on the amount of respirtory syncytial virus (RSV) in the respiratory tract (nasopharynx) of otherwise healthy children hospitalized with RSV infection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Single Intravenous Dose of MEDI-524, a Humanized Enhanced Potency Monoclonal Antibody to Respiratory Syncytial Virus (RSV), in Otherwise Healthy Children Hospitalized With RSV Infection
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Jan 1, 2005
• Actual Study Completion Date: Jan 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Motavizumab, 3 mg/kg as a single intravenous dose Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Biological: Motavizumab; Single dose of Motavizumab at a dose of 3 mg/kg administered intravenously (in the vein) on Day 0; Other Names: MEDI-524
Experimental: Motavizumab, 15 mg/kg as a single intravenous dose Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Biological: Motavizumab; Single dose of Motavizumab at a dose of 15 mg/kg administered intravenously (in the vein) on Day 0; Other Names: MEDI-524
Experimental: Motavizumab, 30 mg/kg as a single intravenous dose Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Biological: Motavizumab; Single dose of Motavizumab at a dose of 30 mg/kg administered intravenously (in the vein) on Day 0; Other Names: MEDI-524
Placebo Comparator: Placebo, as a single intravenous dose Placebo, as a single intravenous dose administered on Day 0	Other: Placebo; Single dose of placebo administered intravenously (in the vein) on Day 0

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting Adverse Events Through 30 Days After Dosing [From the start of treatment to 30 days after dosing]

   Safety and tolerability of motavizumab (MEDI-524) was measured by adverse events through 30 days after dosing

2. Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing [From the start of treatment to 30 days after dosing]

   Safety and tolerability of motavizumab (MEDI-524) was measured by serious adverse events through 30 days after dosing

3. The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations [From the start of treatment to 30 days after dosing]

   Safety and tolerability of motavizumab (MEDI-524) was measured by the occurrence of increased toxicity grade from baseline as determined by laboratory evaluations (complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and urinalysis) at baseline and at each study collection time point following dosing

4. To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 [Day 2 and Day 30]

   Mean trough serum concentrations of motavizumab (MEDI-524) were collected on Day 2 and on Day 30. Serum concentrations of MEDI-524 were analysed using a qualified enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

1. To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 [Immediately before dosing on Day 0]

   The serum anti-motavizumab antibody titers were measured in subjects on Day 0 (before dosing). Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.

2. To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 [Day 30]

   The serum anti-motavizumab antibody titers were measured in subjects on Day 30. Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Previously healthy

• Age 24 months and younger at the time of randomization

• Gestational age of 36 weeks gestation and older

• Randomization within 24 hours after hospitalization

• Hospitalized for lower respiratory tract illness (ie, respiratory syncytial virus (RSV) bronchiolitis and/or pneumonia) documented by positive RSV antigen detection or culture in respiratory secretions within 72 hours before randomization

Exclusion Criteria:

• Already received or would receive ribavirin or other anti-viral treatment for the current episode of RSV infection prior to randomization

• Required intubation for ventilatory support

• Any medically significant underlying ongoing chronic illness or organ system dysfunction or other known acute illness, other than RSV infection

• Known renal impairment, hepatic dysfunction, hematologic abnormalities, seizure or other neurologic disorder or immunodeficiency

• Requirement for supplemental oxygen at any time prior to the current RSV infection (brief use of oxygen in the immediate postnatal period to treat a transient condition was allowed)

• Mechanical ventilation at any time prior to the onset of the current RSV infection

• Congenital heart disease (children with medically or surgically corrected patent ductus arteriosus [PDA], small atrial septal defect [ASD] or ventricular septal defect [VSD] were allowed)

• Previous reaction to intravneous immunoglobulin (IVIG), blood products, or other foreign proteins

• Prior use of IVIG, RSV-IGIV (RespiGam), palivizumab (Synagis), or other immunoglobulin products within the past 2 months

• Currently receiving other investigational agents or have received any other investigational agents within the last 3 months

• Prior or current participation in any investigational study with a therapeutic agent or vaccine for RSV

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: Genevieve A Losonsky, MD, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00192504
• Other Study ID Numbers: MI-CP106
• First Posted: Sep 19, 2005
• Last Update Posted: Oct 8, 2021
• Last Verified: Oct 1, 2006

• Keywords provided by , ,: MEDI-524; Motavizumab; respiratory syncytial virus; children; intravenous; Rezield
• Additional relevant MeSH terms: Respiratory Syncytial Virus Infections

Study Results

Participant Flow

Pre-assignment Detail	The screening period occurred within 24 hours before randomization. All subjects who were screened were randomized into the study.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Period Title: Overall Study
STARTED	5	5	6	15
COMPLETED	4	5	5	15
NOT COMPLETED	1	0	1	0

Baseline Characteristics

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo	Total
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0	Total of all reporting groups
Overall Participants	5	5	5	15	30
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	8.84 (6.62)	3.18 (1.56)	10.78 (9.07)	7.43 (7.69)	7.51 (7.19)
Sex: Female, Male (Count of Participants)
Female	2 40%	4 80%	1 20%	3 20%	10 33.3%
Male	3 60%	1 20%	4 80%	12 80%	20 66.7%
Race/Ethnicity, Customized (Number) [Number]
White/Non-Hispanic	1 20%	0 0%	1 20%	1 6.7%	3 10%
Hispanic	4 80%	5 100%	4 80%	14 93.3%	27 90%
Region of Enrollment (participants) [Number]
Chile	4 80%	5 100%	4 80%	14 93.3%	27 90%
United States	1 20%	0 0%	1 20%	1 6.7%	3 10%
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	8.728 (1.392)	5.516 (0.891)	9.194 (3.43)	7.386 (3.218)	7.599 (2.903)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting Adverse Events Through 30 Days After Dosing
Description	Safety and tolerability of motavizumab (MEDI-524) was measured by adverse events through 30 days after dosing
Time Frame	From the start of treatment to 30 days after dosing

Outcome Measure Data

Analysis Population Description

All patients who recieved study drug were included in the analysis of safety.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	5	5	5	15
Number [Participants]	3 60%	5 100%	3 60%	6 40%

2. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing
Description	Safety and tolerability of motavizumab (MEDI-524) was measured by serious adverse events through 30 days after dosing
Time Frame	From the start of treatment to 30 days after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	4	5	5	15
Number [participants]	0 0%	0 0%	1 20%	1 6.7%

3. Secondary Outcome

Title	To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0
Description	The serum anti-motavizumab antibody titers were measured in subjects on Day 0 (before dosing). Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.
Time Frame	Immediately before dosing on Day 0

Outcome Measure Data

Analysis Population Description

All patients who received a full dose of study drug were included in the analysis of immunogenicity.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	5	5	5	15
Number [Participants]	0 0%	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30
Description	The serum anti-motavizumab antibody titers were measured in subjects on Day 30. Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

All patients who received a full dose of study drug were included in the analysis of immunogenicity. One patient in the 3 mg/kg group was not assessed for immunogenicity.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	4	5	5	15
Number [Participants]	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations
Description	Safety and tolerability of motavizumab (MEDI-524) was measured by the occurrence of increased toxicity grade from baseline as determined by laboratory evaluations (complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and urinalysis) at baseline and at each study collection time point following dosing
Time Frame	From the start of treatment to 30 days after dosing

Outcome Measure Data

Analysis Population Description

All patients who recieved study drug were included in the analysis of safety.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	5	5	5	15
Number [Participants]	0 0%	1 20%	1 20%	1 6.7%

6. Primary Outcome

Title	To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30
Description	Mean trough serum concentrations of motavizumab (MEDI-524) were collected on Day 2 and on Day 30. Serum concentrations of MEDI-524 were analysed using a qualified enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 2 and Day 30

Outcome Measure Data

Analysis Population Description

All patients who recieved a full dose of study drug were included in the analysis of trough serum concentrations. One patient in the 3 mg/kg group was not assessed for serum trough levels at either Day 2 or Day 30.

Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg	Motavizumab (MEDI-524), 15 mg/kg	Motavizumab (MEDI-524), 30 mg/kg	Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0	Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0	Placebo, as a single intravenous dose administered on Day 0
Measure Participants	4	5	5	15
Trough Serum Concentration at Day 2	61.78 (20.09)	170.8 (38.43)	333.2 (99.86)	0 (0)
Trough Serum Concentration at Day 30	16.63 (13.08)	59.18 (12.72)	80.28 (27.34)	0 (0)

Adverse Events

Time Frame	Adverse events were collected from the time of the first administration of motavizumab (MEDI-524) to 30 days after dosing.
Arm/Group Title	Motavizumab (MEDI-524), 3 mg/kg		Motavizumab (MEDI-524), 15 mg/kg		Motavizumab (MEDI-524), 30 mg/kg		Placebo
Arm/Group Description	Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0		Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0		Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0		Placebo, as a single intravenous dose administered on Day 0
All Cause Mortality
	Motavizumab (MEDI-524), 3 mg/kg		Motavizumab (MEDI-524), 15 mg/kg		Motavizumab (MEDI-524), 30 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Motavizumab (MEDI-524), 3 mg/kg		Motavizumab (MEDI-524), 15 mg/kg		Motavizumab (MEDI-524), 30 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		1/5 (20%)		1/15 (6.7%)
Infections and infestations
Epstein-Barr virus infection	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Motavizumab (MEDI-524), 3 mg/kg		Motavizumab (MEDI-524), 15 mg/kg		Motavizumab (MEDI-524), 30 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		5/5 (100%)		3/5 (60%)		6/15 (40%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Leukocytosis	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	2/15 (13.3%)	2
Eye disorders
Eyelid oedema	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Gastrointestinal disorders
Diarrhoea	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Disbacteriosis	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Vomiting	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	1/15 (6.7%)	1
General disorders
Oedema	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Pyrexia	0/5 (0%)	0	1/5 (20%)	1	1/5 (20%)	1	3/15 (20%)	4
Infections and infestations
Bronchitis	1/5 (20%)	1	2/5 (40%)	2	0/5 (0%)	0	3/15 (20%)	3
Gastroenteritis rotavirus	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Genital infection fungal	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Haemophilus infection	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Lower respiratory tract infection	2/5 (40%)	2	1/5 (20%)	1	0/5 (0%)	0	2/15 (13.3%)	2
Nasopharyngitis	1/5 (20%)	1	1/5 (20%)	1	1/5 (20%)	1	0/15 (0%)	0
Otitis media	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Otitis media acute	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Pseudomonal bacteraemia	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Superinfection bacterial	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Upper respiratory tract infection	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/15 (6.7%)	1
Urinary tract infection	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Viral skin infection	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Investigations
Alanine aminotransferase increased	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/15 (0%)	0
Aspartate aminotransferase increased	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/15 (0%)	0
Cardiac murmur	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Metabolism and nutrition disorders
Hypocalcaemia	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Hypokalaemia	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Hypophosphataemia	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Allergic respiratory symptom	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Skin and subcutaneous tissue disorders
Heat rash	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Rash erythematous	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Rash macular	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/15 (0%)	0
Skin erosion	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/15 (0%)	0
Vascular disorders
Haemodynamic instability	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0
Hypertension	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

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.