Alfamino^® Meets American Academy of Pediatrics Criteria for Hypoallergenicity in Children With Confirmed Cow's Milk Allergy

Background

Cow's milk allergy (CMA) is a major food allergy in infancy and childhood. The American Academy of Pediatrics (AAP) defines a formula as hypoallergenic when clinical testing demonstrates, with 95% confidence, that at least 90% of individuals with confirmed CMA will not react under double-blind, placebo-controlled conditions.

Objective

To determine whether a new amino acid-based formula (AAF; test formula, subsequently marketed as Alfamino®) met AAP criteria for hypoallergenicity in infants and children with documented CMA.

Study Design

• Design: Randomized, double-blind, active-controlled, crossover food-challenge study followed by a 7- to 9-day at-home open challenge with the test formula.
• Population: Infants and children with documented CMA, recruited at 6 U.S. sites. Thirty-seven subjects were enrolled; mean age was 4.6 years.
• Intervention: Double-blind placebo-controlled food challenges (DBPCFCs) with both the test AAF and a commercial control AAF (Neocate®), administered 2–7 days apart in randomized sequence.
• DBPCFC exposure: Total planned formula volume was 180 mL for subjects ≤1 year and 240 mL for subjects >1 year, with standardized assessment of skin, respiratory, gastrointestinal and cardiovascular signs/symptoms.
• Open challenge: Subjects who passed both DBPCFCs were instructed to consume at least 8 oz/day of the test formula for 1 week, while recording intake, stool characteristics, GI symptoms, potential allergic symptoms and adverse events.
• Primary endpoint: Demonstration that the lower bound of the one-sided 95% confidence interval for the proportion without allergic reactions was at least 90%.

Formula Comparison

Results

33 subjects completed both DBPCFCs. No subjects experienced an allergic reaction to either the test formula or control formula during the DBPCFCs.

• AAP hypoallergenicity criterion achieved: the lower bound of the 95% confidence interval for hypoallergenicity was 91.3%, exceeding the AAP requirement of 90%.
• Open challenge: all 33 DBPCFC completers participated. Thirty consumed at least 8 oz of test formula on at least 5 days.
• GI tolerance: no unusual stool patterns or characteristics, flatulence, or spit-up were reported during the open challenge.
• Reported events: four subjects reported vomiting on at least one occasion, attributed to palatability. One subject reported perioral erythema, one itchy skin on the back, and one a mild stomachache. These events were self-resolving and did not lead to cessation of test formula.
• Safety: no serious adverse events were reported.

Discussion

The randomized crossover DBPCFC design directly assessed acute allergic reactivity to the test and control AAFs in children with well-documented CMA. The authors report that the test formula met the prespecified AAP hypoallergenicity criterion. The subsequent home challenge provided additional short-term observations on intake and tolerance.

Study considerations

• The primary hypoallergenicity analysis was based on the 33 subjects who completed both DBPCFCs. Four of 37 randomized subjects discontinued their first DBPCFC because of formula taste; no signs of a positive allergic reaction were observed in those subjects.
• The open challenge was short (7–9 days) and conducted at home rather than under controlled challenge conditions.
• The study was supported by Nestlé Health Science. Two authors were employees of Nestlé Nutrition.