A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety of MEDI-559 in Healthy 1 to <24 Month-Old Children

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00767416
• Collaborator: (none)
• Enrollment: 116
• Locations: 76
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 1 to <24 months of age.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: MEDI-559; Other: Placebo	Phase 1/Phase 2

Detailed Description

This is a randomized, double-blind, placebo-controlled, multi-dose, Phase 1/2a multi-center trial to evaluate the safety, tolerability, viral shedding, immunogenicity, and genotypic and phenotypic stability of MEDI-559 in RSV seronegative infants 5 to <24 months of age and in infants 1 to <3 months of age regardless of baseline serostatus. The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 5 to <24 months of age and to healthy infants 1 to <3 months of age regardless of baseline serostatus.

MEDI-559 will be administered at a dose of 10^{5 fluorescent focus units (FFU) on a 0, 2, and 4 month schedule to two cohorts of subjects in a step-wise fashion. The target sample size for this study is 320 subjects, with 160 subjects 5 to <24 months of age enrolled into Cohort 1 and 160 subjects 1 to <3 months of age enrolled into Cohort 2. Each cohort will be randomized 1:1 (MEDI-559 to placebo) and stratified by site. Cohort 1 will initiate dosing at 10}5 FFU MEDI-559. Blinded safety data from the first 40 subjects enrolled in Cohort 1 for the 28 days following administration of the first dose of vaccine will be reviewed. If no safety concerns are noted, Cohort 2 will initiate dosing at 10^5 FFU. Enrollment into Cohort 2 will be halted after approximately 40 subjects have been randomized, and blinded safety data will be reviewed through 28 days post Dose 1. If no safety concerns are noted, the remainder of Cohort 2 will be enrolled. All subjects will be followed through 365 days after randomization to ensure that each subject has been followed through an RSV season.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Viral Shedding of MEDI-559, a Live Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus in Healthy 1 to <24 Month-Old Children
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 MEDI-559 MEDI-559	Biological: MEDI-559; Cohort 1 (5 to <24 months): N=80 MEDI-559 at 10^5 FFU at 0, 2, and 4 months; frozen preparation filled into 0.5 ml luer slip-tip syringes. Each 0.2 ml dose contains 10^5 FFU MEDI-559 in a sucrose phosphate glutamate buffer.
Placebo Comparator: Cohort 1 Placebo Placebo	Other: Placebo; Cohort 1 (5 to < 24 months); N = 80 placebo at 0, 2, and 4 months; frozen preparation filled into 0.5 ml luer slip-tip syringes. Each 0.2 ml dose contains sucrose phosphate buffer.

Outcome Measures

Primary Outcome Measures

1. Incidence of solicited symptoms after Dose 1 [Through Day 28 after each dose]

   Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis

2. Incidence of solicited symptoms after Dose 2 [Through Day 28 after each dose]

   Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis

3. Incidence of solicited symptoms after Dose 3 [Through Day 28 after each dose]

   Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis

4. Incidence of adverse events (AEs) after Dose 1 [Through Day 28 after each dose]

   As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

5. Incidence of AEs after Dose 2 [Through Day 28 after each dose]

   As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

6. Incidence of AEs after Dose 3 [Through Day 28 after each dose]

   As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

7. Incidence of medically-attended lower respiratory illnesses (MA-LRIs) after Dose 1 [Through Day 28 after each dose]

   An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea

8. Incidence of MA-LRIs after Dose 2 [Through Day 28 after each dose]

   An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea

9. Incidence of MA-LRIs after Dose 3 [Through Day 28 after each dose]

   An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea

10. Incidence of SAEs [Administration of Dose 1 (Day 0) through Day 28 post final dose]

    An SAE is any adverse event that results in any of the following outcomes: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly/birth defect (in the offspring of a subject); an important medical event that may not result in death, threaten life or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

Secondary Outcome Measures

1. Incidence of MEDI-559 shedding [Day 7-10 after Dose 1, 2, and 3]

   Number (%) of subjects who shed vaccine-type virus

2. Incidence of MEDI-559 shedding [Day 12-18 after Dose 1, 2, and 3]

   Number (%) of subjects who shed vaccine-type virus

3. Incidence of MEDI-559 shedding [Day 28-34 post Dose 1, 2, and 3]

   Number (%) of subjects who shed vaccine-type virus

4. Post-vaccination seroresponse against RSV [Day 28 post final dose]

   Seroresponse is defined as a ≥ 4-fold rise from baseline as measured by microneutralization assay

5. Phenotypic stability of recovered vaccine-type virus [Day 7-10 post any dose]

   Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable

6. Phenotypic stability of recovered vaccine-type virus [Day 12-18 post any dose]

   Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable

7. Phenotypic stability of recovered vaccine-type virus [Day 28-34 post any dose]

   Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable

8. Genotypic stability of recovered vaccine-type virus [Day 7-10 post any dose]

   Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable

9. Genotypic stability of recovered vaccine-type virus [Day 12-18 post any dose]

   Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable

10. Genotypic stability of recovered vaccine-type virus [Day 28-34 post any dose]

    Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable

11. Incidence of MA-LRIs [Study Day 0 through 365 days post randomization]

    Number (%) of subjects with MA-LRIs occurring from Study Day 0 through the end of study

12. Incidence of SAEs [Study Day 0 post Dose 1 through 365 days post randomization]

    Number (%) of subjects with SAEs occurring from Study Day 0 through 365 days post randomization

13. Incidence of significant new medical conditions (SNMCs) [Study Day 0 post Dose 1 through 365 days post randomization]

    Number (%) of subjects with SNMCs from administration of Dose 1 through 365 days post randomization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 23 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female whose age on the day of randomization falls within one of the two age cohorts: Cohort 1: 5 to <24 months (reached their 5th month birthday but not yet reached their 2nd year birthday); Cohort 2: 1 to < 3 months (>28 days of age and not yet reached their 3rd month birthday)

• Cohort 1 only: Subject is seronegative to RSV at screening

• Subject was the product of normal full term pregnancy (defined as 36-42 weeks gestation)

• Subject is in general good health

• Written informed consent and HIPAA authorization (if applicable) obtained from the subject's legal representative

• Subject's legal representative is willing and able to bring the subject to the study site for evaluation of respiratory illness in accordance with the protocol

Exclusion Criteria:

• Any fever (≥ 100.4°F [≥ 38.0°C]), regardless of route within 7 days prior to randomization

• Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization

• Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of vaccine

• Cohort 1 only: weight ≤ 5th percentile for age on the day of randomization

• Cohort 2 only: history of low birth weight (ie, <2500 grams at birth) or weight ≤ 5th percentile for age on the day of randomization

• Living in the same home or enrolled in the same classroom at day care with infants <6 months of age within 28 days after each dose (only one child per household may be enrolled into the study)

• Contact with pregnant caregiver within 28 days after each dose

• Living in a household with someone who is immunocompromised within 28 days after each dose; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after each study vaccine dosing

• Living in a household with someone who works in the healthcare field and who has direct patient care responsibilities within 28 days after each dose

• Living in a household with someone who is a day care provider or preschool teacher for children <6 months of age within 28 days after each dose

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Greenville	Alabama	United States	36037
2	Research Site	Huntsville	Alabama	United States	35802
3	Research Site	Mobile	Alabama	United States	36608
4	Research Site	Conway	Arkansas	United States	72034
5	Research Site	Little Rock	Arkansas	United States	72202
6	Research Site	Little Rock	Arkansas	United States	72205
7	Research Site	Anaheim	California	United States	92804
8	Research Site	Cypress	California	United States	90630
9	Research Site	Downey	California	United States	90241
10	Research Site	Huntington Beach	California	United States	92647
11	Research Site	Lakewood	California	United States	90712
12	Research Site	Long Beach	California	United States	90806
13	Research Site	Los Angeles	California	United States	90015
14	Research Site	Los Angeles	California	United States	90024
15	Research Site	Paramount	California	United States	90723
16	Research Site	San Diego	California	United States	92103
17	Research Site	Santa Ana	California	United States	92705
18	Research Site	Thornton	Colorado	United States	80223
19	Research Site	Hartford	Connecticut	United States	06106
20	Research Site	Washington	District of Columbia	United States	20058
21	Research Site	Miami	Florida	United States	33142
22	Research Site	Miami	Florida	United States	33155
23	Research Site	Orange City	Florida	United States	32763
24	Research Site	Tampa	Florida	United States	33606
25	Research Site	Dalton	Georgia	United States	30721
26	Research Site	Chicago	Illinois	United States	60614
27	Research Site	Fishers	Indiana	United States	46037
28	Research Site	New Albany	Indiana	United States	47150
29	Research Site	South Bend	Indiana	United States	46601
30	Research Site	Ames	Iowa	United States	50010
31	Research Site	Bardstown	Kentucky	United States	40004
32	Research Site	Lexington	Kentucky	United States	40503
33	Research Site	Lexington	Kentucky	United States	40509
34	Research Site	Louisville	Kentucky	United States	40202
35	Research Site	Louisville	Kentucky	United States	40207
36	Research Site	Paducah	Kentucky	United States	42003
37	Research Site	Metarie	Louisiana	United States	70006
38	Research Site	Fredrick	Maryland	United States	21215
39	Research Site	Boston	Massachusetts	United States	02111
40	Research Site	Fall River	Massachusetts	United States	02724
41	Research Site	Bridgeton	Missouri	United States	63044
42	Research Site	Kansas City	Missouri	United States	64132
43	Research Site	Omaha	Nebraska	United States	68131
44	Research Site	Omaha	Nebraska	United States	68134
45	Research Site	Brooklyn	New York	United States	11219
46	Research Site	Endwell	New York	United States	13760
47	Research Site	Stony Brook	New York	United States	11794
48	Research Site	Syracuse	New York	United States	13210
49	Research Site	Cleveland	Ohio	United States	44109
50	Research Site	Cleveland	Ohio	United States	44121
51	Research Site	Huber Heights	Ohio	United States	45424
52	Research Site	Norman	Oklahoma	United States	73071
53	Research Site	Tulsa	Oklahoma	United States	74127
54	Research Site	Warwick	Rhode Island	United States	02886
55	Research Site	Spartanburg	South Carolina	United States	29303
56	Research Site	Franklin	Tennessee	United States	37067
57	Research Site	Jackson	Tennessee	United States	38305
58	Research Site	Johnson City	Tennessee	United States	37604
59	Research Site	Kingsport	Tennessee	United States	37660
60	Research Site	Corpus Christi	Texas	United States	78414
61	Research Site	Houston	Texas	United States	77036
62	Research Site	Houston	Texas	United States	77055
63	Research Site	San Angelo	Texas	United States	76904
64	Research Site	San Antonio	Texas	United States	78205
65	Research Site	San Antonio	Texas	United States	78229
66	Research Site	San Antonio	Texas	United States	78258
67	Research Site	Tomball	Texas	United States	77375
68	Research Site	Layton	Utah	United States	84041
69	Research Site	St. George	Utah	United States	84790
70	Research Site	Syracuse	Utah	United States	84075
71	Research Site	Charlottesville	Virginia	United States	22902
72	Research Site	Colonial Heights	Virginia	United States	23834
73	Research Site	Midlothian	Virginia	United States	23113
74	Research Site	Richmond	Virginia	United States	23219
75	Research Site	Walla Walla	Washington	United States	99362
76	Research Site	Caguas		Puerto Rico	00726

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: Joseph Sliman, M.D., MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• MEDI-559_CP-147_Protocol_Redacted_13Nov13

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT00767416
• Other Study ID Numbers: MI-CP147
• First Posted: Oct 7, 2008
• Last Update Posted: Jul 20, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by MedImmune LLC: MEDI-559; Respiratory Syncytial Virus; RSV; Pediatric; Vaccine; respiratory syncytial virus, RSV, pediatric, vaccine

Study Results

No Results Posted as of Jul 20, 2016