Safety and Efficacy Evaluation of an Extensively Hydrolyzed Formula in Infants With Cow's Milk Protein Allergy (CMPA)

Safety and Efficacy Evaluation of Extensively Hydrolyzed Formula for Cow's Milk Protein Allergy (CMPA) in Infants and Young Children

This is a prospective, multi-center, randomized, open-label, active-controlled, parallel-group, non-inferiority study. The goal of this clinical trial is to evaluate the clinical efficacy and safety of an extensively hydrolyzed formula (eHF) in treating infants with mild-to-moderate cow's milk protein allergy (CMPA).

CMPA is a common condition in babies where the immune system reacts to proteins in cow's milk, causing symptoms affecting the skin (such as eczema or hives), gastrointestinal tract (such as vomiting, diarrhea, or constipation), and respiratory system (such as runny nose or wheezing).

The study plans to enroll 124 infants aged 0-5 months who have been diagnosed with mild-to-moderate CMPA by a physician based on established diagnostic criteria.

The main questions it aims to answer are:

1. Does this new formula effectively relieve CMPA symptoms? Relief is defined as a reduction in severity from baseline for at least one scored symptom (skin, gastrointestinal, or respiratory) observed during study visits. The overall symptom relief rate at Day 28 will be calculated as: (number of effective cases / total number of cases) × 100%.
2. What medical problems or side effects do infants experience when using this formula? Researchers will compare the new formula (Feihe Extensively Hydrolyzed Formula) to an already approved extensively hydrolyzed formula (a standard treatment for CMPA) to see if the new formula works as well (non-inferiority).

Eligible participants will be randomly assigned (like drawing lots) in a 1:1 ratio to either the test group or the control group. The randomization process will be stratified by age: infants aged >0 to ≤2 months (targeting 40% of participants) and infants aged >2 to ≤5 months (targeting 60% of participants). A centralized interactive web response system (IWRS) will be used to ensure unbiased assignment.

Study Duration and Visits:

The study will last approximately 28 days. After the initial screening visit (V0), participants will need to visit the clinic 3 times:

• Visit 1 (V1, Day 0, before taking the study product): Baseline assessments
• Visit 2 (V2, Day 14 ± 1 day): Follow-up assessments
• Visit 3 (V3, Day 28 ± 1 day): Final assessments

What Participants Will Do:

• Receive study formula: At V1 and V2, researchers will provide enough formula until the next visit. At V2 and V3, parents should return any empty cans.

• Undergo medical assessments: At each visit (V1, V2, V3), the doctor will:

  • Assess atopic dermatitis severity using the SCORAD tool (combining physical examination with parent-reported itching and sleep quality)
  • Assess nasal and eye symptoms (and asthma symptoms, if applicable) using the VAS
  • Assess gastrointestinal, skin, and respiratory symptoms using the CoMiSS
  • At the final visit (V3), evaluate overall treatment effectiveness based on symptom improvement
• Have growth measurements taken: At each visit, researchers will measure the infant's weight (in grams), length (in cm), and head circumference (in cm). Growth velocity and Z-scores will be calculated.

• Complete parent questionnaires: At each visit, parents will:

  • Report on the infant's itching and sleep for the SCORAD assessment
  • Complete the IGSQ to assess gastrointestinal symptoms
  • Use the BSFS pictures to help describe the infant's stool form
• Collect stool samples: Before each visit (V1, V2, V3), parents will collect a small stool sample (about 4-5 grams) using a provided kit. These samples will be tested for routine analysis and occult blood.
• Maintain a feeding diary: From V1 to V3, parents will keep a daily diary recording the amount of study formula consumed and any breastfeeding.
• Report health events: Inform the study team of any illnesses, discomfort, or medications the infant experiences throughout the study.
• Undergo optional bone density testing: At each visit, an ultrasound bone density measurement may be performed at the clinic's discretion.

Study Overview

• Status: Not yet recruiting
• Conditions: Cow's Milk Protein Allergy (CMPA)
• Intervention / Treatment: Other: Feihe Extensively Hydrolyzed Formula; Other: Nestlé Extensively Hydrolyzed Formula

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shaojie Pang; Phone Number: +8613001298033; Email: pangshaojie@feihe.com
• Study Contact Backup: Name: Fei Xu; Phone Number: +8613391512691; Email: love_faith@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 102208
      • Beijing Jingdu Children's Hospital
      • Contact: Tao An; Phone Number: +8613621324860; Email: wwaa7576@126.com
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Foshan Maternal and Child Health Hospital
      • Contact: Saijun Huang; Phone Number: +8618038831089; Email: tufanqie@163.com
    • Zhuhai, Guangdong, China, 519000
      • Zhuhai Maternal and Child Health Hospital
      • Contact: Hongjun Chen; Phone Number: +8613823092202; Email: zhfy-chj@163.com
  • Hunan
    • Xiangtan, Hunan, China, 411200
      • Xiangtan County Maternal and Child Health Hospital
      • Contact: Fengyun Li; Phone Number: +8615873289995; Email: 762185394@qq.com
  • Jiangsu
    • Wuxi, Jiangsu, China, 214000
      • Wuxi Maternal and Child Health Hospital
      • Contact: Xinye Jiang; Phone Number: +8613814201725; Email: fyjxy2110@163.com
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Jinxin Xinan Women's and Children's Hospital
      • Contact: Shuhua Ren; Phone Number: +8613880856194; Email: renshuhua@jxyl.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for participation:

• Born at 37-42 weeks gestation with birth weight 2500-4000 g
• Aged 0 to 5 months at enrollment

• Diagnosed with mild-to-moderate CMPA by a physician based on the Nowak-Wegrzyn (2019) diagnostic criteria, meeting any of the following prior to enrollment:

  (a) Typical allergic symptoms + sensitization markers

• Symptoms: Clear allergic reactions (e.g., urticaria, vomiting, dyspnea) following exposure to cow's milk or dairy products

• Evidence of sensitization (any one of the following):

  • Serum cow's milk-specific IgE >0.7 kIU/L
  • Serum cow's milk-specific IgE >0.35 kUA/L
  • Positive skin prick test (wheal diameter ≥5 mm) (b) High-threshold serum specific IgE
• Infants aged <1 year: Cow's milk-specific IgE ≥5 kIU/L (c) Strongly positive SPT
• SPT wheal diameter ≥10 mm (regardless of age) (d) Positive oral food challenge under medical supervision
• Dietary elimination for at least 2 weeks, followed by OFC provoking immediate allergic reactions (e) Physician-confirmed diagnosis
• Physician-confirmed diagnosis of CMPA supported by medical records dated within 2 weeks
• Written informed consent voluntarily signed by at least one parent or legal guardian
• Parents or legal guardians able to understand the informed consent form and other study documents, and willing and able to comply with study requirements
• Parents or legal guardians agree not to enroll the infant in any other clinical studies during the trial period

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for participation:

• Recent onset of allergic symptoms due to causes other than cow's milk protein (including other food allergens, inhalant allergies, contact allergies, drug allergies, insect bite allergies, etc.)
• Use of any extensively hydrolyzed formula (eHF) or amino acid formula (AAF) for the treatment of cow's milk protein allergy within 1 month prior to enrollment
• Known intolerance to ingredients in the study formula (e.g., lactose intolerance)
• Severe cow's milk protein allergy requiring treatment with amino acid formula (AAF)
• Presence of severe congenital diseases or malformations, major organ dysfunction, genetic or metabolic disorders, or infectious diseases of the gastrointestinal tract or other sites
• Growth retardation due to causes other than cow's milk protein allergy, or other significant medical conditions that, in the opinion of the investigator, may affect growth and/or development
• Need for specialized diets or feeding methods (e.g., amino acid formula, metabolic disorder formula, or tube feeding)
• Complementary foods already introduced
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study
• Concurrent participation in another clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Feihe Extensively Hydrolyzed Formula	Other: Feihe Extensively Hydrolyzed Formula; Feihe Extensively Hydrolyzed Formula： Nutritional Characteristics: Protein is extensively hydrolyzed into peptides and amino acids to reduce allergenicity. Enriched with MCT for rapid energy, DHA/ARA for neurodevelopment, and OPO for improved fatty acid and calcium absorption. Contains vitamins and minerals to meet full nutritional needs. Dosage and Administration: To be used under medical supervision. Dosage is individualized based on infant's age, weight, and clinical condition. Standard reconstitution: 3 level scoops (approx. 4.5 g/scoop) added to 90 mL of potable water. Intended as a sole source of nutrition for infants up to 6 months; for older infants, complementary foods may be added as advised by a physician.
Active Comparator: Nestlé Extensively Hydrolyzed Formula	Other: Nestlé Extensively Hydrolyzed Formula; Nestlé Extensively Hydrolyzed Formula： Nutritional Characteristics: Protein is extensively hydrolyzed into peptides and amino acids to reduce allergenicity. Enriched with MCT for rapid energy, DHA/ARA for neurodevelopment, and OPO for improved fatty acid and calcium absorption. Contains 26 vitamins and minerals to meet full nutritional needs. Dosage and Administration: To be used under medical supervision. Dosage is individualized. Standard reconstitution: 13.5 g powder (3 level scoops, approx. 4.5 g/scoop) added to 90 mL of cooled boiled water to obtain 100 mL of feed. Intended as a sole source of nutrition for infants up to 6 months with food protein allergy; for older infants, complementary foods may be added under medical guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Relief Rate of Cow's Milk Protein Allergy (CMPA)	The proportion of infants showing improvement in CMPA symptoms. Effectiveness is defined as a reduction in severity from baseline for at least one scored symptom (skin, gastrointestinal, or respiratory) observed during study visits. No improvement in any symptoms or signs during the intervention is considered ineffective. The total effective rate is calculated as: (number of effective cases / total number of cases) × 100%.	At Day 28 (allowing a window of ± 1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scoring Atopic Dermatitis (SCORAD) Score	Scoring Atopic Dermatitis (SCORAD) score assessing the severity of atopic dermatitis by combining physician assessment of lesion extent and intensity with parent-reported pruritus and sleep loss.	Baseline, Day 14 ± 1, Day 28 ± 1
Infant Gastrointestinal Symptom Questionnaire (IGSQ) Score	Infant Gastrointestinal Symptom Questionnaire (IGSQ) total score assessing gastrointestinal symptoms including stooling, spitting up/vomiting, crying, fussiness/irritability, and gas.	Baseline, Day 14 ± 1, Day 28 ± 1
Visual Analogue Scale (VAS) Score	Visual Analogue Scale (VAS) score assessing nasal symptoms (sneezing, rhinorrhea, nasal itching, congestion) and ocular symptoms (itching, foreign body sensation, redness, lacrimation). For infants with comorbid asthma, asthma symptoms (wheezing, coughing, shortness of breath, chest tightness) are also recorded. Based on objective symptoms and signs, the physician evaluates improvement in individual symptom scores as well as total scores for nasal, ocular, and asthma symptoms.	Baseline, Day 14 ± 1, Day 28 ± 1
Bristol Stool Form Scale (BSFS) Score	Assessment of stool form. This scale is a 7-point visual chart featuring pictorial representations and textual descriptions of different stool forms, ranging from Type 1 (separate hard lumps) to Type 7 (watery stool).	Baseline, Day 14 ± 1, Day 28 ± 1
Cow's Milk-related Symptom Score (CoMiSS) Score	Cow's Milk-related Symptom Score (CoMiSS) assessing gastrointestinal, skin, and respiratory symptoms associated with CMPA. It provides a reference for healthcare professionals to monitor the evolution of symptoms through assessment and quantification during the course of treatment.	Baseline, Day 14 ± 1, Day 28 ± 1
Stool Samples Test Results	Presence of abnormalities in stool routine examination and fecal occult blood test results.	Baseline, Day 14 ± 1, Day 28 ± 1
Growth Parameters	Change from baseline in weight (g), length (cm), head circumference (cm), growth velocity (g/day, cm/day), and Z-scores (WAZ, LAZ, HCAZ, WLZ) based on WHO growth standards.	Baseline, Day 14 ± 1, Day 28 ± 1
Bone Mineral Density (Optional)	Change from baseline in ultrasound bone mineral density measurements (SOS value, Z-score, percentage) if performed.	Baseline, Day 14 ± 1, Day 28 ± 1
Adverse Events and Concomitant Medications	Incidence, severity, and relationship to study product of adverse events and serious adverse events, as well as concomitant medication use, throughout the study period.	From first dose to Day 28 ± 1

Collaborators and Investigators

• Sponsor: Heilongjiang Feihe Dairy Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 5, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: FEIHE-INF2508-001

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