| Study summary: |
|
This trial is divide into two groups, subjects from birth to 8 months of age and subjects 8
months of age to 3 years of age. Depending upon the age group, subjects are in the study
for up to 4 months (for the younger age group) or 2 weeks (for the older age group).
Study description for the Birth to 8 month age group:
Infants who qualify will begin a 7-day milk protein elimination diet that excludes all milk
or products which contain milk. Parents will be asked to keep a food diary of everything
the child eats during the week following the Screening Visit. During this week, the child
can continue to drink their current hypoallergenic formula.
At study visit 2 the subject will be given a double-blind, randomized food challenge with up
to 5 doses of each study formula over a 1-hour period. Each formula will be given in 5
increasing amounts (1/4 teaspoon, about 1 teaspoon, 1 teaspoon, about 3 tablespoons, and 3
1/3 tablespoons).
This test is done to see if the subject has any allergic reaction to either of the 2 study
formulas. The test takes about 6 hours to complete because it includes a 2-hour observation
period between drinking the 2 formulas. If the subject has an allergic reaction to either
study formula, the subject will not continue with the study.
Subjects who are eligble to continue will be given a 1 week supply of the test formula, a
study diary, and a food diary. Parents will be asked to record everything their child eats
and any symptoms he/she may have for 1 week.
The subject will return for 5 additional study visits. Subjects will continue to be given
study formula for the rest of the study. During the study, parents will also be asked to
collect stool samples.
This study is expected to last a little over 4 months and will include 7 study visits.
Procedures for subjects' birth up to 8 months old:
Subjects will be assessed at seven study visits at baseline, two weeks, four weeks and then
monthly until the end of the study period, where the following will be assessed:
Study Visit 1 (Day -7): Baseline
This will be carried out at entry to the trial to collect baseline data; at this visit
subjects will under go the following assessments:
Assess Patient suitability Obtain Informed Consent Obtain Subject number Perform physical
exam and clinical assessment Medical history and assessment including SCORing Atopic
Dermatitis assessment (SCORAD) Obtain weight, length and head circumference Collect a 9ml
venous blood sample The following is to analysed by the central lab; Plasma total
protein/albumin and prealbumin Blood urea nitrogen, electrolytes and creatinine Complete
blood count with differential Alkaline phosphatase. Serum Iron, Total Iron Binding Capacity
and Ferritin Plasma fatty acid analysis Provide stool lab kits and explain to
parent/caregiver how to collect stool sample during the pre-evaluation week Provide one-week
subject diary (Subject Diary 1) and instruct parent/caregiver on how to complete record,
clinical symptoms and stool characteristics (frequency, consistency and color) in subject
diary.
Provide the one-week Food Frequency Diary A and instruct the parent/caregiver on how to
complete this assessment Provide information on following a milk protein exclusion diet,
with or without the exclusion of other allergenic food proteins as advised by the subject's
physician Record all concomitant medications taken within two weeks prior to the Baseline
Visit
Study Visit 2 (Day 0): Double-blind Placebo Controlled Formula Challenge (DBPCFC)(Phase I)
Once subjects have completed the pre-evaluation period subjects will undergo the following
assessment:
Review Subject Diary 1 and Food Frequency Diary A, for study compliance Randomisation
assignment to determine order of challenges Perform physical exam and clinical assessment
Complete the DBPCFC Obtain weight, length/height and head circumference Provide two-week
subject diary (Subject Diary 2a) and instruct parent/caregiver on how to record clinical
symptoms and stool characteristics in subject diary.
Provide the one-week Food Frequency Diary B and instruct the parent/caregiver on how to
complete this assessment Collect stool sample that was obtained in previous week at home
Subject to commence seven-day, post challenge feeding period with blinded study formula the
subject was first exposed to during the DBPCFC Dispense study product
Subjects who show clinical symptoms consistent with an allergic reaction during DBPCFC will
be considered as failing the challenge and be terminated from the study. Reactions should
be recorded by the supervising clinician and will be noted in the screening log. In the
event that a clinical reaction is observed during the DBPCFC or during the one-week feeding
period following the challenge procedure, the subject will be discontinued from the study.
Once a sufficient number of subjects have completed the DBPCFC and seven-day post-challenge
feeding period with the test formula, Phase I will be completed and no further subjects in
the 8 months to 3 years old group will be enrolled. Enrollment of infants aged from birth
up to 8 month old will continue, however they will no longer be required to undergo the
DBPCFC. Randomization will occur by using the formula that they should first have been
exposed to if they had undergone the DBPCFC. The Sponsor will notify all sites when this
change in procedure should occur. Following this change subjects will undergo all Visit 2
activities, except for the DBPCFC.
Phone review (Day 7) Subjects will be reviewed at this time point by telephone to review if
any clinical symptoms have occurred while ingesting study formula. If it is determined by
the Principal Investigator that the subject has had any clinically significant reaction(s)
to the study formula, the subject must return to the clinic for evaluation. Subjects will
progress to Phase II and continue feeding with the formula they have consumed as part of the
seven-day, post-challenge feeding period.
Study Visit 3 (Day 14): Two weeks on formula
Once subjects have been consuming their assigned formula for a two week period the following
assessment will be carried out:
Obtain weight, length and head circumference Collect Subject Diary 2a and Food Frequency
Diary B Review of open feeding period and presence of any clinical symptoms Provide one-week
subject diary (Subject Diary 3) to be completed the week before returning for Visit 4 and
instruct parent/caregiver on how to record, clinical symptoms and stool characteristics in
subject diary.
Provide three-day Food Diary 1 to be completed the week before returning for visit 4 and
instruct parent/caregiver on how to complete the food records Instruct parent to collect
stool sample during the week before study Visit 4. Review study product requirement and
dispense as necessary
Study Visit 4 (Day 28): One month on formula
Once subject have been consuming test formula for one month they will undergo the following
assessment:
Perform clinical assessment and SCORAD Obtain weight, length and head circumference Obtain
stool sample collected by parent Collect and review Subject Diary 3 and Food Diary 1 Review
study product requirement and dispense as necessary
Study Visit 5 (Day 56): Two months on formula Obtain weight, length and head circumference
Provide 3 day subject diary (Subject Diary 4) to be completed in the following week and
instruct parent/caregiver on how to record clinical symptoms and stool characteristics in
subject diary Provide three-day Food Diary 2 to be completed in the following week and
instruct parent/caregiver on how to complete the food records Review study product
requirement and dispense as necessary
Study Visit 6 (Day 84): Three months on formula Obtain weight, length and head circumference
Collect Subject Diary 4 and Food Diary 2 Provide one week subject diary (Subject Diary 5) to
be completed in the week prior to the final study visit and instruct parent/caregiver on how
to complete the food records, clinical symptoms and stool characteristics in subject diary
Provide three-day Food Diary 3 to be completed in the week prior to the final study visit
and instruct parent/caregiver on how to complete the food records Instruct parent to take
stool sample during the week before the final study visit Review study product requirement
and dispense as necessary
Study Visit 7 (Day 112): Final visit - four months on formula or Early Termination Perform
clinical assessment and SCORAD Obtain weight, length and head circumference Obtain stool
sample collected by parent Collect and review Subject Diary 5 and Food Diary 3 Collect blood
sample Ensure Parents/caregivers have returned all diaries to the appropriate clinician at
each center Study personnel will review the forms with the parents/caregivers
Parents/caregivers will return all partial and unopened cans of the test formula
Study description for the 8 month to 3 year age group:
Infants who qualify will begin a 7-day milk protein elimination diet that excludes all milk
or products which contain milk. Parents will be asked to keep a food diary of everything
the child eats during the week following the Screening Visit. During this week, the child
can continue to drink their current hypoallergenic formula.
At study visit 2 the subject will be given a double-blind, randomized food challenge with up
to 5 doses of each study formula over a 1-hour period. Each formula will be given in 5
increasing amounts (1/4 teaspoon, about 1 teaspoon, 1 teaspoon, about 3 tablespoons, and 3
1/3 tablespoons).
This test is done to see if your child has any allergic reaction to either of the 2 study
formulas. The test takes about 6 hours to complete because it includes a 2-hour observation
period between drinking the 2 formulas. If the subject has an allergic reaction to either
study formula, the subject will not continue with the study.
Subjects who are eligble to continue will be given a 1 week supply of the test formula, a
study diary, and a food diary. Parents will be asked to record everything their child eats
and any symptoms he/she may have for 1 week. The subject will return in about 1 week for a
final study visit.
The study is expected to last about 2 weeks and will include 3 study visits. |
| Criteria: |
|
Inclusion Criteria:
1. Subjects aged from birth to 3 years old with documented allergy to cow milk protein
are eligible to enter the study. Subjects with other IgE or non IgE mediated
allergies to food in addition to milk protein (e.g. multiple food allergy or an
eosinophilic disorder) are also eligible to enter the study. However all subjects
must have a confirmed allergy to milk confirmed by one of the following criteria,
within two months prior to the baseline visit:
- Positive double-blind placebo controlled food challenge with cow milk
- A confirmed history of acute severe reaction after isolated accidental ingestion
with a positive test result for IgE antibody
- Confirmed history of a reaction to cow milk protein with CM-specific IgE of
>15kU/L for children over two years and > 5kU/L for children under two years.
- Confirmed clinical history of a reaction to cow milk protein with a positive
skin prick test with a resulting wheal diameter greater or equal to 3mm.
- No confirmed clinical history of a reaction to cow milk protein subjects with a
positive skin prick test with a resulting wheal diameter greater or equal to 8mm
for children over 2 years and greater or equal to 6mm for children under 2
years.
- For children with an Allergic Eosinophilic Gastroenteritis (AEG), documentation
of eosinophilic infiltration and resolution of symptoms on a diet that
restricted cow milk (and other foods) with reoccurrence after re-administration
of cow milk.
2. Written informed consent / ability to give informed consent.
Subjects aged from birth up to 8 months of age;
3. Suitable for inclusion into Phase I and II of the study.
4. These subjects are expected to consume a minimum intake of test formula to ensure an
average daily intake, which provides at least 50% of their daily energy requirements,
during the seven-day, post challenge feeding period and the Phase II growth
assessment.
Subjects aged over 8 months to 3 years old
5. Suitable for inclusion into Phase I only
6. These subjects are expected to consume a minimum of 8 fl. oz per day of study formula
during the seven-day, post-challenge feeding period
Exclusion Criteria:
All subjects
1. Infants <5lb 8oz at birth
2. Infants < 37 weeks gestation
3. Infants with severe concurrent illness or major congenital malformations
4. Suspected or documented systemic or congenital infections (e.g. human
immunodeficiency virus)
5. Unable to adhere to protocol instructions due to non compliance of parent or
caregiver
6. Investigator's uncertainty about the willingness or ability of the patient to comply
with the protocol requirements
7. Participation in any other studies involving investigational products concomitantly
or within twenty eight days prior to entry into the study
8. An infant of any personnel connected with the study
9. Infants whose parent/caregiver is younger than the legal age of consent
Subjects aged from birth up to 8 months of age;
10. For these subjects the dietary consumption of other sources of prebiotics or
probiotics is prohibited two weeks prior to inclusion in the study and during the
study period.
11. These subjects must not have received systemic antibiotics in the previous two weeks
prior to entry into the study. |