Tolerance and Growth Outcomes of an Extensively Hydrolysed Anti-regurgitation Casein-based Formula in Infants With Cow's Milk Protein Allergy (PANDA)

Tolerance and Growth Outcomes of an Extensively Hydrolysed Anti-regurgitation Casein-based Formula in Infants With Cow's Milk Protein Allergy: a Clinical Evaluation

This study is designed as multicentric, interventional, with two successive randomised, double-blind, crossovers. The aim of the study is to demonstrate the tolerance of an extensively hydrolysed anti-regurgitation casein-based formula in infants with cow's milk protein allergy. After a confirmation of the diagnostic, this demonstration will be performed with oral food challenge. Secondarily, a long term tolerance phase will be performed to get growth outcomes with a consumption of the formula compared with a non-enriched formula.

Study Overview

• Status: Not yet recruiting
• Conditions: FPIES; Cow Milk Protein Allergy
• Intervention / Treatment: Other: Oral Food Challenge V2; Other: Oral Food Challenge V3; Other: Product administration between V4 and V5; Other: Product administration between V5 and V6

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grégory ALLAIN; Phone Number: +33 6 65 74 91 49; Email: gregory.allain@biofortis.fr
• Study Contact Backup: Name: Basile FRILLEY; Phone Number: +33 6 64 08 92 96; Email: basile.frilley@biofortis.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

I1. Age ≥ 1 month and < 9 months, I2. Exclusively formula fed and planning to be formula-fed for the duration of the study (food diversification allowed),

I3. With:

1. a suspicion of CMPA based on suggestive allergic symptoms

   • CoMISS score > 10
   • And/or acute allergic symptoms
   • And/or symptoms suggestive of a Food Protein-Induced Enterocolitis Syndrome (FPIES) (major criteria and <3 minor criteria as per consensus guidelines) (Nowak-Węgrzyn et al. 2017; Beaudoin et al. 2025); OR

2. a confirmed diagnosis of CMPA within the two months before inclusion:

   • IgE-mediated CMPA (documented history of allergic reaction grade ≤ 3 according to the ordinal food allergy severity score oFASS-5 (Fernández-Rivas et al. 2022) following milk protein ingestion, and sensitization to CMP: blood IgE level specific to cow milk≥ 5 kU/L, or positive skin prick test with papule with fresh cow's milk ≥ 8 mm
   • or non-IgE-mediated CMPA (documented history of eviction/reintroduction test concluding to CMPA),
   • or FPIES (major criteria and ≥3 minor criteria as per consensus guidelines (Nowak-Węgrzyn et al. 2017; Beaudoin et al. 2025), I4. With a written informed consent signed by the father and mother or legal representative(s), I5. With parents willing to complete questionnaires, records, and diaries associated to the study and to complete all clinical visits, I6. With parents willing to achieve all study interventions, I7. At least one of the legal representatives is affiliated with a social security scheme.

Exclusion Criteria:

E1. Birthweight < 2500 g, E2. Gestational age < 37 weeks, E3. Breastfeeding at the time of inclusion and throughout the study period, E4. Already fed with an AAF, or with the investigational formula EHF-AR, E5. History of anaphylactic reaction grade 4 or 5 according to classification oFASS-5 (Fernández-Rivas et al. 2022), or of severe FPIES (previous reaction with any change in behaviour from baseline, any pallor and dehydration requiring intravenous fluids), after mammalian milk exposure, E6. Diagnosed or reported fever and/or infectious diseases, or current systemic infections, or history of congenital infections,

E7. History / diagnosis of:

1. GI disease or abnormalities (i.e. short bowel syndrome, chronic intestinal diseases, or GI malformations),
2. Or Other malformations, congenital cardiovascular, kidney, liver, pancreas, metabolic or neurological diseases,
3. Or Immunodeficiency, or chronic infection requiring long-term treatment,
4. Or Genetic diseases and chromosomal abnormalities, E8. Suspected or confirmed food allergies or intolerances, other than CMPA, E9. Currently enrolled in another clinical study, or in exclusion period from a previous clinical study, E10. Whose legal representatives have psychological or linguistic incapability to sign the informed consent, E11. Impossibility to contact the legal representatives in case of emergency.

After V1, the participant will be excluded from participation in this trial if he/she fulfils the following criteria:

E12. No allergic symptoms following the OFC with a standard CMPF.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: First cross-over : EHF-STD / AAF; At V2 visit, an OFC is performed with EHF-STD (extensively hydrolysed anti-regurgitation casein-based formula). At V3 visit, an OFC is performed with AAF (amino acid formula).	Other: Oral Food Challenge V2; At V2, a randomization is performed and a product is allocated to be administrated in an OFC. According to the randomization the product is EHF-AR or AAF. The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.; Other: Oral Food Challenge V3; At V3, the second product is administrated (EHF-AR or AAF)(cross-over). The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.
Other: First cross-over : AAF / EHF-AR; At V2 visit, an OFC is performed with AAF (amino acid formula). At V3 visit, an OFC is performed with EHF-STD (extensively hydrolysed anti-regurgitation casein-based formula).	Other: Oral Food Challenge V2; At V2, a randomization is performed and a product is allocated to be administrated in an OFC. According to the randomization the product is EHF-AR or AAF. The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.; Other: Oral Food Challenge V3; At V3, the second product is administrated (EHF-AR or AAF)(cross-over). The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.
Other: Second cross-over : EHF-AR / EHF-STD; From V4 to V5 visit, the subject consumes EHF-AR (extensively hydrolysed anti-regurgitation casein-based formula). From V5 to V6 visit, the subject consumes EHF-STD (extensively hydrolysed casein-based formula).	Other: Product administration between V4 and V5; At V4, a randomization is performed and a product is allocated for the consumption between V4 and V5. According to the randomization, the product is EHF-AR or EHF-STD. The patient will be fed this product for 2 months.; Other: Product administration between V5 and V6; At V5, a second allocation is performed and the second product is consumed between V5 and V6 (EHF-AR or EHF-STD)(crossover). The patient will be fed this product for 2 months.
Other: Second cross-over : EHF-STD / EHF-AR; From V4 to V5 visit, the subject consumes EHF-STD (extensively hydrolysed casein-based formula). From V5 to V6 visit, the subject consumes EHF-AR (extensively hydrolysed anti-regurgitation casein-based formula).	Other: Product administration between V4 and V5; At V4, a randomization is performed and a product is allocated for the consumption between V4 and V5. According to the randomization, the product is EHF-AR or EHF-STD. The patient will be fed this product for 2 months.; Other: Product administration between V5 and V6; At V5, a second allocation is performed and the second product is consumed between V5 and V6 (EHF-AR or EHF-STD)(crossover). The patient will be fed this product for 2 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of infants with CMPA who do not experience any allergic symptoms.	The proportion of infants with CMPA who do not experience any allergic symptoms that lead to study discontinuation, as per the investigator, during the first week following the OFC with the EHF-AR formula, including the OFC period itself (between V2 and V3, or V3 and V4).	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of the CoMISS subscores	Variation of the CoMISS subscores (crying, regurgitation, stools, respiratory symptoms, and skin signs) (expressed in arbitrary unit (a.u.), range 0-33) between: V4 and PC2; V5 and PC3; V4 and V5,; V5 and V6.	9 months
Variation of the IGSQ score	Variation of the IGSQ score (expressed in a.u., range 13-65) from V4 to V5, and from V5 to V6.	9 months
Number of TEAEs	Total number of TEAEs in the allergy body system; Total number of TEAEs in the gastrointestinal body system; Total number of TEAEs	9 months
Z-scores for age of anthropometric parameters	Z-scores for age of anthropometric parameters (length (cm), weight (g) and head circumference (cm)) at V4, V5 and V6	9 months
Parents' satisfaction	Rate of parents' answer to the following questions: "Did your baby accept the formula well?" at PC2 and PC3 (yes / somewhat / no),; "Did the formula reduce your baby's spit-up symptoms?" at PC2 and PC3 (yes / somewhat / no / not applicable (no symptoms)),; "Are you generally satisfied with the formula?" at V5 and V6 (yes / somewhat / no),; "Would you recommend this formula to other parents?" at V5 and at V6 (yes / no / no opinion).	9 months

Collaborators and Investigators

• Sponsor: Lactalis
• Investigators: Study Director: GUERVILLE Mathilde, Lactalis; Study Director: Charlotte MAGNANT, Lactalis; Principal Investigator: Anaïs LEMOINE, Hôpital Armand Trousseau - APHP

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2025-A01706-43

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