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.

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