Trial Outcomes & Findings for Efficacy and Safety Evaluation in Recurrent Wheezing Attacks (NCT NCT01734811)

NCT ID: NCT01734811

Last Updated: 2021-11-08

Results Overview

Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 120 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2021-11-08

Participant Flow

October 2012 - May 2015 subjects enrollment. 120 children <3 years old with recurrent WA, defined as 3 or more episodes of WA during the previous year. . WA were confirmed by the review of the medical records. Aeroallergen sensitization at baseline was used as an exclusion criterion to avoid an eventual WA due to allergic asthma.

Participant milestones

Measure	Placebo The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Overall Study STARTED	58	62
Overall Study COMPLETED	54	59
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Measure	Placebo The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Overall Study Lost to Follow-up	2	3
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Efficacy and Safety Evaluation in Recurrent Wheezing Attacks

Baseline characteristics by cohort

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	58 Participants n=5 Participants	62 Participants n=7 Participants	120 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	23 Months STANDARD_DEVIATION 8 • n=5 Participants	23 Months STANDARD_DEVIATION 7 • n=7 Participants	23 Months STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	37 Participants n=7 Participants	69 Participants n=5 Participants
Region of Enrollment Spain	58 participants n=5 Participants	62 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Number of Recurrent Bronchospasm (Wheezing Attacks)	299 events	176 events

SECONDARY outcome

Timeframe: 12 months

Review of bronchospasm (wheezing attacks) duration per patient

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Duration (Days) of Wheezing Attacks (WA)	7.9 days Interval 6.2 to 11.0	6.0 days Interval 4.0 to 9.5

SECONDARY outcome

Timeframe: 12 months

time (days) until appearance of first wheezing attack (WA)

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Time Until Appearance of First WA	5.0 days Interval 2.0 to 28.8	41.0 days Interval 15.0 to 94.5

SECONDARY outcome

Timeframe: 12 months

Review of the number of days with wheezing attacks during the study

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Number of Days With Wheezing Attacks During the Study	42.0 days Interval 17.0 to 57.5	19.2 days Interval 8.5 to 35.0

SECONDARY outcome

Timeframe: 12 months

Review of number of patients with recurrent WA during the whole study

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Number of Patients With Recurrent WA During the Study	45 Participants	36 Participants

SECONDARY outcome

Timeframe: 12 months

Total of Symptom score during wheezing attacks. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed.

Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3.

The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC.

The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Symptom Score During Wheezing Attacks	155.0 units on a scale Interval 79.0 to 244.5	80.0 units on a scale Interval 19.5 to 154.5

SECONDARY outcome

Timeframe: 12 months

Review of medication consumption during wheezing attacks. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed.

Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded.

The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Medication Score During WA	424.0 units on a scale Interval 185.0 to 738.5	164.0 units on a scale Interval 43.5 to 311.5

SECONDARY outcome

Timeframe: 12 months

Review of symptoms during the whole study. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed.

Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3.

The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC.

The total symptom score was calculated as the sum of all individual scores during the whole study

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Overall Symptom Score	421.0 units on a scale Interval 303.0 to 673.0	276.5 units on a scale Interval 151.0 to 426.0

SECONDARY outcome

Timeframe: 12 months

Review of medication consumption during the whole study. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed.

Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded.

The total symptom score was calculated as the sum of all individual scores during the whole study.

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Overall Medication Score	1043.5 units on a scale Interval 669.5 to 1696.0	618.5 units on a scale Interval 318.3 to 1035.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

The use of health and social resources during the study was also recorded: days of hospitalization in ward and/or intensive care unit, visits to the emergency units, unscheduled visits to the pediatrician and/or to the specialist, telephone calls to the pediatrician, complementary tests (chest radiogram, blood analysis, others), days of school absenteeism and caregiver-days when the children needed them. The data were obtained from the diary cards and confirmed through the review of medical records.

Maximum value corresponds to the maximum days spent in health resources (specified above) and the minimum value corresponds to the minimum of days spent in health resources (specified above)

Outcome measures

Measure	Placebo n=58 Participants The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 Participants The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Use of Health and Social Resources During the Whole Period of the Study.	14.5 days Interval 2.0 to 52.0	11.0 days Interval 0.0 to 44.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Biological Vaccine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=58 participants at risk The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Biological Vaccine n=62 participants at risk The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Nervous system disorders Epilectic seizure	1.7% 1/58 • Number of events 1 • Up to 12 months. Adverse Events were registered throughout the trial. Grading was according to EAACI guidelines.	0.00% 0/62 • Up to 12 months. Adverse Events were registered throughout the trial. Grading was according to EAACI guidelines.

Other adverse events

Adverse event data not reported

Additional Information

Medical Director

Inmunotek

Phone: 916 510 010

Email: mcasanovas@inmunotek.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place