The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy

• The proportion of patients who maintain a clinical response after withdrawal of treatment for one week. [ Time Frame: Approximately 1 1/2 years. ] [ Designated as safety issue: No ]
• The proportion of patients who maintain a clinical response after withdrawal of treatment for six weeks. [ Time Frame: Approximately 1 1/2 years. ] [ Designated as safety issue: No ]
• Incidence of all serious adverse events during the study [ Time Frame: Approximately 1 1/2 years. ] [ Designated as safety issue: Yes ]
• Incidence of all adverse events during the study. [ Time Frame: Approximately 1 1/2 years. ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine if small oral and sublingual doses of milk protein are safe and effective in decreasing sensitivity to cow's milk in allergic children.

• Drug: Milk Protein Extract Immunotherapy
  Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.
• Drug: Milk Protein Extract Immunotherapy
  Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.
• Drug: Milk Powder Immunotherapy
  Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.
• Drug: Milk Powder Immunotherapy
  Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.

• Experimental: 1
  These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 2000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year.
  Interventions:

  • Drug: Milk Protein Extract Immunotherapy
  • Drug: Milk Powder Immunotherapy
• Experimental: 2
  These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 1000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year.
  Interventions:

  • Drug: Milk Protein Extract Immunotherapy
  • Drug: Milk Powder Immunotherapy
• Experimental: 3
  These subjects will have a dose escalation of the milk protein extract given sublingually. After dose escalation, they will continue on the sublingual daily maintenance dose for approximately one year.
  Intervention: Drug: Milk Protein Extract Immunotherapy

Inclusion Criteria:

• Are age 6 to 21 years
• Provide signed informed consent (by parent or legal guardian if the subject is a minor), and informed assent if applicable
• Have a history of symptomatic reactivity to cow's milk (i.e. Eczema, urticaria, upper or lower respiratory symptoms, GI disturbances, other rash or oral symptoms)
• Have a positive skin prick test (defined as wheal 3 mm ≥ negative control) and cow's milk-IgE > 0.35 kIU/L
• Have a positive OFC to cow's milk at a cumulative dose of less than 184 milligrams of cow's milk intact protein (2,400 mg total milk protein).
• Are using appropriate birth control if subject is female and of child bearing age.
• Have self-injectable epinephrine (ie. EpiPen® or EpiPen Jr.®) available at home

Exclusion Criteria:

• Have a history of severe anaphylaxis defined as hypoxia (cyanosis or SpO2 ≤ 92% at any stage), hypotension, confusion, collapse, loss of consciousness; or incontinence
• Have a history of intubation related to asthma
• Tolerate more than 184 milligrams of intact cow's milk protein at initial OFC
• Are pregnant or lactating
• Have a viral URI or gastroenteritis within 7 days of OFC (OFC needs to be rescheduled)
• Have pulmonary function tests <80% of predicted (FEV1) or clinical history consistent with more than moderate persistent asthma
• Are currently taking greater than medium dose inhaled corticosteroid (>400 mcg/day fluticasone or fluticasone equivalent if ≤ 12 years old or > 600 mcg/day if > 12 years old)
• Are unable to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or food challenges
• Have used systemic corticosteroids within 4 weeks prior to baseline visit
• Are receiving omalizumab, beta-blocker, ACE inhibitor or tricyclic antidepressant therapy
• Have a chronic disease (other than asthma, atopic dermatitis or rhinitis) requiring therapy (e.g., heart disease, diabetes)
• Have participated in any interventional study for treatment of a food allergy in the past 12 months
• Have a severe reaction at initial DBPCFC, defined as either:

Life-threatening anaphylaxis, or Reaction requiring hospitalization

• Duke University
• Greer Laboratories