Evaluation of Tolerance, Efficacy and Safety of an Hydrolyzed Formula in Infants With IgE/Non-IgE Mediated CMA. (MERLIN)

Cow's Milk Allergy (CMA): Evaluation of Tolerance, Efficacy and Safety of a Thickened Extensively Hydrolyzed Formula in Infants With IgE and Non-IgE Mediated CMA

The aim of this interventional study is to assess the hypoallergenicity of a new formula in infants having a cow milk allergy (CMA), whatever the type of CMA, meaning in both IgE-mediated and non-IgE-mediated CMA patients.

This will be tested through a double-blind placebo controlled food challenge (DBPCFC) taking place over 2 or 3 separate days, in hospital.

If the child tolerates the tested formula during the DBPCFC, he will be fed with the test formula during the second study phase. There will be monthly visit and parents will be asked to fill in diaries.

Study Overview

• Status: Active, not recruiting
• Conditions: Cow's Milk Allergy
• Intervention / Treatment: Dietary supplement: Test Formula; Dietary supplement: Placebo Formula

Detailed Description

Briefly, on two separate days, the placebo formula and the TEHCF will be introduced at increasing doses under medical supervision, and appearance of allergic symptoms will be witnessed and recorded if any. The week after, and more particularly the 72 hours after each food challenge day, child's parents will be instructed to report to the investigator any delayed reaction that may occur. In case the TEHCF induces an allergic reaction, the child's participation will be ended. Otherwise, the child will enter the second study part, lasting 4 months and during which the usual formula taken by the child will be totally replaced by the TEHCF.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Begium
    • Namur, Begium, Belgium, 5000
      • Private practice Elena BRADATAN
• Italy
  • Roma, Italy, 00161
    • University Hospital - Umberto I Sapienza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• between 1 and 24 months old
• having a CMA proven in the last 3 months prior to inclusion
• free of clinical allergic symptoms for at least one week (i.e., successfully fed an elimination diet)
• whose parent(s)/legal guardian(s) signed the informed consent form.

Main Exclusion Criteria:

• Children mainly (>1 breastfeeding/day) or exclusively breastfed, with maternal willingness to continue breast-feeding
• Children with a mean formula intake lower than 250 ml/day
• Children with past anaphylactic reaction(s)

• Children with chronic (non acute) FPIES

  -- Children presenting with any situation which, according to the investigator, may interfere with the study participation, or lead to a particular risk for the subject,

• Children already participating in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Formula; Infants will receive an extensively hydrolyzed formula during the double-blind placebo-controlled food challenge (DBPCFC) and will continue on this formula during the open-label feeding phase if they tolerate it.	Dietary supplement: Test Formula; Infants will receive an extensively hydrolyzed formula during the double-blind placebo-controlled food challenge (DBPCFC) and will continue on this formula during the open-label feeding phase if they tolerate it.; Dietary supplement: Placebo Formula; Infants will receive a placebo formula during the DBPCFC to compare against the test formula.
Placebo Comparator: Placebo Formula; Infants will receive a placebo formula (=their previous formula) during the DBPCFC to compare against the test formula.	Dietary supplement: Test Formula; Infants will receive an extensively hydrolyzed formula during the double-blind placebo-controlled food challenge (DBPCFC) and will continue on this formula during the open-label feeding phase if they tolerate it.; Dietary supplement: Placebo Formula; Infants will receive a placebo formula during the DBPCFC to compare against the test formula.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoallergenicity of the formula	the percentage of children tolerating the formula during the double blind placebo controlled food challenge	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cow's Milk Related Symptom Score (CoMiSS™)	The Cow's Milk Related Symptom Score (CoMiSS™) will be evaluated globally and each of its subscore. CoMiSS ranges from 0 to 33 (worst outcome).	At each visit : day7, day 30, day 60, day 90 and day 120
Atopic dermatitis severity - SCORing Atopic Dermatitis (SCORAD) Index	Atopic dermatitis is assessed using the SCORing Atopic Dermatitis (SCORAD) Index. The score ranges from 0 to 103 (most severe state) and is used to determine the stages of severity of AD.	At each visit : day7, day 30, day 60, day 90 and day 120
Gastrointestinal CMA symptoms	the other Gastrointestinal CMA symptoms (not described by the COMISS) will be reported (such as acute diarrhea, constipation...)	At each visit : day7, day 30, day 60, day 90 and day 120
Cutaneous CMA symptoms	Others Cutaneous CMA symptoms besides those evaluated in the CoMISS and the SCORAD will be described	At each visit : day7, day 30, day 60, day 90 and day 120
Sleep characteristics	This measures focuses on evaluating the quality and duration of sleep in children consuming the test.	At each visit : day7, day 30, day 60, day 90 and day 120
Weight	Weight will be expressed in kg and in z scores according to the World Health Organization (WHO) Child Growth Standards.	At each monthly visit day 30, day 60, day 90 and day 120
Height	Height will be expressed in cm and in z scores according to the WHO Child Growth Standards.	At each monthly visit day 30, day 60, day 90 and day 120
Head circumference	Head circumference will be expressed in cm and in z scores according to the WHO Child Growth Standards.	At each monthly visit day 30, day 60, day 90 and day 120
BMI	BMI will be expressed in value and z scores according to the WHO Child Growth Standards.	At each monthly visit day 30, day 60, day 90 and day 120
Adverse event	Any untoward medical reaction occuring from the signatture of the consent until the end of the participant's participation	During the whole study duration
Compliance	It will be assessed through the volume of formula consumed	At each visit : day7, day 30, day 60, day 90 and day 120
Parents' satisfaction	Satisfaction regarding the effect of the study formula on regurgitations, stool consistency, digestive comfort, and the acceptability of the formula by the child will be evaluated by using a 5-level satisfaction scale (very satisfied/satisfied/unsatisfied/very unsatisfied / without opinion)	At each visit : day7, day 30, day 60, day 90 and day 120
Investigator's satisfaction	paediatrician's satisfaction with the effect of the study formula on the child) will be assessed by using a 4-level satisfaction scale (very satisfied/satisfied/unsatisfied/very unsatisfied).	At each visit : day7, day 30, day 60, day 90 and day 120
Digestive tolerance	Digestive tolerance of the formula will be assessed by monitoring stool frequency and consistency, regurgitations, abdominal pain/painful flatus/ bloating, crying time, irritability time.	At each visit : day7, day 30, day 60, day 90 and day 120

Collaborators and Investigators

• Sponsor: United Pharmaceuticals
• Collaborators: Slb Pharma
• Investigators: Principal Investigator: Salvatore OLIVA, MD, PhD, University Hospital - Umberto I

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CMA (Cow's Milk Allergy); DBPCFC (Double-Blind Placebo-Controlled Food Challenge); FA (Food Allergy); IgE (Immunoglobulin E); OFC (Oral Food Challenge)
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Food Hypersensitivity; Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: UP2022-01-MERLIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No