TeriFort 1+ Study: Efficacy and Safety of an Extensively Hydrolyzed Formula in the Management of Cow's Milk Protein Allergy in Young Children: A Prospective, Single-Arm Interventional Study (TeriFort 1+)

Cow's milk protein allergy (CMPA) is one of the most common food allergy in infancy and early childhood. The global overall prevalence ranges from 0.5% to 3% , and in some regions it can be as high as 4.9%. Currently, there are no nationwide epidemiological survey data on CMPA in China. However, local studies conducted in Chongqing, Hangzhou, and Zhuhai have reported a prevalence of 0.83% \~ 3.5% in infants aged 0 \~ 2 years. The pathogenesis of CMPA mainly includes IgE-mediated immediate-type hypersensitivity, non-IgE-mediated delayed-type hypersensitivity, and mixed-type reactions mediated by both mechanisms. Clinical manifestations may involve multiple organs and systems, including the skin, gastrointestinal tract, and respiratory tract. Dietary avoidance of cow's milk protein continues to be the main therapeutic approach, utilizing extensively hydrolyzed or amino acid-based formulas as determined by the degree of allergy.

Ages 1 \~ 3 years represent a critical window for the persistence of allergic symptoms and disease resolution in toddlers; approximately 85% \~ 90% of children with CMPA achieve clinical tolerance by around 3 years of age. Meanwhile, the age group of 1 \~ 3 years is also a critical period for dietary transition and the establishment of immune tolerance, during which children are particularly vulnerable to nutritional deficiencies. Therefore, special attention should be given to this age group, so that early diagnosis and appropriate interventions can be implemented to mitigate the impact of the disease on growth and development.

This is a prospective, longitudinal, single-arm study conducted at 1 hospital in China. The study will enroll young children aged 1\~ 3 years with diagnosed with or highly suspected CMPA. Each participant will be followed for 90 days after the initiation of the investigational product. Parents or legal guardians will complete questionnaires regarding symptoms, gastrointestinal function, and product acceptability, while investigators will record clinical symptoms and anthropometric data using an electronic case report form (eCRF).

Collected data will include:

* Sociodemographic and baseline characteristics: sex, birth weight and length, gestational age, and family history of allergy.
* Anthropometric parameters: weight, length, and head circumference.
* Clinical assessments: Modified CoMiSS, SCORAD, and BSFS scores.
* Parent-reported outcomes: IGSQ-13, FAQL-PB, BISQ scores,and acceptability/satisfaction surveys.
* Safety outcomes: adverse events and concomitant medications.

A healthy reference group will include, which underwent only the modified CoMiSS assessment without exposure to the investigational product or involvement in efficacy/safety analyses, yielding normative reference benchmarks for the healthy population.

• Diagnosed with or highly suspected CMPA: Extensively Hydrolyzed Formula intervention (Other): * Avoidance of all foods and products containing cow's milk protein will be required; * An individualized diet will be selected and arranged according to the young children's usual eating habits, with dietary guidance provided by the investigator based on the young children's allergic status; * The intake of the investigational product will be recommended to be maintained at approximately 500 mL/day.

Primary outcomes

• Change in investigator-reported allergy symptom scores [Baseline, Day 30 ± 5, Day 90 ± 7]: Change from baseline to D30 and D90 in investigator-assessed allergy symptoms in toddlers with diagnosed with or highly suspected cow's milk protein allergy, measured using four instruments.

Secondary outcomes

• Change in investigators measured or parent/caregiver-reported allergy symptom scores [Baseline, Day 30 ± 5, Day 60 ± 7, Day 90 ± 7]: Change from baseline to D30, D60 and D90 in investigators measured or parent/caregiver-reported symptoms, which will be analyzed according to improvement (reduction in score) or no improvement.
• Change in z-scores for weight, length/height, and head circumference [Baseline, Day 30 ± 5, Day 90 ± 7]: Change in z-scores for weight, length/height, and head circumference calculated according to World Health Organization (WHO) growth standards. Differences between baseline, D30 and D90 will be summarized using descriptive statistics.
• Change in stool characteristics [Baseline, Day 30 ± 5, Day 60 ± 7, Day 90 ± 7]: Parent-reported stool characteristics (consistency and color), stool frequencies and stool types will be summarized for each visit.
• Stool Samples Test Results [Baseline, Day 30 ± 5, Day 90 ± 7]: Abnormalities in routine stool examination and fecal occult blood test.
• Change in parental quality of life related to children allergy [Baseline, Day 30 ± 5, Day 60 ± 7, Day 90 ± 7]: Change in the Food Allergy Quality of Life-Parental Burden Questionnaire (FAQL-PB) score from baseline to Day 30, Day 60 and day 90. Improvement will be defined as a reduction in the total score. Descriptive statistics and frequencies of improvement will be presented.
• Parental satisfaction with the investigational product [Day 90 ± 7]: Parent- or caregiver-reported satisfaction with the investigational product.
• Dietary intake [Baseline, Day 30 ± 5, Day 90 ± 7]: Assessment of dietary intake, including food categories and quantities (by weight), at baseline, on Day 30, and on Day 90 of the intervention.
• Adverse Events and Concomitant Medications [From first intervention to Day 90 ± 7]: Incidence, severity, and causal attribution to the study product of AEs and SAEs, together with concomitant medication use, throughout the study period.

Sex: All, ages: 12 Months to 36 Months

Inclusion Criteria:

* 12 months≤ Age <36 months at enrollment.
* Born at term at 37 \~ 42 weeks of gestation, with birth weight 2,500\~4,000g.
* Diagnosed with or highly suspected mild-to-moderate CMPA by a physician, meeting any of the following prior to enrollment:

  1. Positive serum cow's-milk-specific IgE (sIgE) >0.35 kUA/L (>0.7 kIU/L), combined with a detailed medical history; or a positive skin prick test (SPT);
  2. Positive result from a cow's milk protein elimination-challenge test;
  3. A documented medical history confirming CMPA within the 2 weeks prior to enrollment.
* Hospitalization is not required and home intervention is considered appropriate by the investigator.
* Written informed consent signed by a parent or legal guardian.

Exclusion Criteria:

* History of severe cows-milk-induced allergic reaction, such as anaphylactic shock.
* Underlying disease or history that may increase risk or affect gastrointestinal tolerance, growth, or development, including chronic systemic disease, congenital heart disease, chronic inflammatory bowel disease, malignant tumor, gastrointestinal malformation, or major congenital malformation.
* Laboratory abnormalities judged by the investigator to make participation inappropriate.
* Use of an extensively hydrolyzed formula or amino-acid formula within the preceding month.
* Participation in another interventional clinical trial within the preceding 90 days or currently.
* Inability to complete scheduled study visits
* Known intolerance to another ingredient in the study formula
* Any other condition judged inappropriate by the investigator.