Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance (SLIT2)

• Percentage of subjects who demonstrate clinical desensitization by passing the 48 month double-blind, placebo-controlled food challenge. [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
• Induction of clinical tolerance after 48months vs 60 months of peanut SLIT. [ Time Frame: 66 months ] [ Designated as safety issue: Yes ]
• The change in immune parameters over time associated with the induction of tolerance. [ Time Frame: 66 months ] [ Designated as safety issue: No ]
• The change of immune function of those who achieve tolerance versus those who do not achieve tolerance. [ Time Frame: 66 months ] [ Designated as safety issue: No ]

• Percentage of subjects who demonstrate clinical desensitization by passing the 48 month double-blind, placebo-controlled food challenge. [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
• Induction of clinical tolerance after 48months vs 60 months of peanut SLIT. [ Time Frame: 66 months ] [ Designated as safety issue: Yes ]
• The change in immune parameters over time associated with the induction of clinical tolerance versus the failure to achieve clinical tolerance. [ Time Frame: 66 months ] [ Designated as safety issue: No ]

The goal of this study will be to increase the reaction threshold (desensitization) of peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance).

Allergy to peanuts and tree nuts affects approximately 1.4% of the population. Allergic reactions to peanut can be severe and life threatening and account for the vast majority of fatalities due to food-induced anaphylaxis. At present, there are no viable treatment options for patients with peanut allergy. The current standard of care is strict dietary elimination and emergency preparedness with an anaphylaxis kit in the event of an accidental reaction.

Our group and others have shown that oral immunotherapy can provide protection from anaphylaxis to a variety of food proteins. In addition, our ongoing research has demonstrated that sublingual immunotherapy to peanut provides a safe, alternative mode of immunotherapy to reduce allergic reaction rates (desensitization) during oral food challenge to peanut. The goal of this study will be to desensitize peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance). Children ages 1-11 years will be enrolled following an entry double blind, placebo controlled food challenge (DBPCFC). All children will receive peanut sublingual immunotherapy (SLIT) for 48 months and before undergoing a second DBPCFC. Subjects who demonstrate desensitization at this food challenge will be randomized to placebo or continued peanut SLIT for 6 months prior to undergoing a third DBPCFC to assess clinical tolerance. Subjects randomized to continued peanut SLIT will complete 6 additional months of the study drug. At that point, they will discontinue SLIT for 6 months and have a final DBPCFC to assess tolerance at the end of study (66 months). Outcome variables of interest include response to double blind, placebo controlled food challenges, skin prick testing, peanut specific serum IgE, IgG, and IgG4 and salivary IgA, T and B cell responses, basophil hyporesponsiveness, quality of life, and adverse events.

• Peanut Hypersensitivity
• Food Hypersensitivity
• Food Allergy
• Peanut Allergy

• Drug: Liquid peanut extract
  Liquid peanut extract will be administered under the tongue
  Other Name: Peanut SLIT - active arm
• Drug: Placebo Glycerin SLIT
  Liquid glycerin extract will be administered under the tongue
  Other Name: Placebo Glycerin SLIT

• Experimental: Peanut SLIT
  All subjects will receive peanut SLIT upon enrollment for the first 48 months. After the desensitization DBPCFC at 48 months, subjects will be randomized 2:1 to placebo or continued peanut SLIT. The SLIT group will complete 60 months of SLIT prior to undergoing a final DBPCFC at 66 months to assess clinical tolerance.
  Intervention: Drug: Liquid peanut extract
• Placebo Comparator: Placebo Glycerin SLIT
  All subjects will receive peanut SLIT for 48 months upon enrollment. After the desensitization DBPCFC at 48 months, subjects will be randomized 2:1 to placebo or continued peanut SLIT for 6 months and then undergo a DBPCFC to assess clinical tolerance. The placebo subjects will either demonstrate tolerance or be eligible to restart SLIT for the remainder of the study if they fail to achieve tolerance.
  Intervention: Drug: Placebo Glycerin SLIT

Inclusion Criteria:

• Age 1-11 years
• Peanut specific IgE > 0.35kU/L or a convincing clinical history of an allergic reaction to peanut within 1 hour of ingestion
• Positive entry DBPCFC to 1 gram of peanut protein

Exclusion Criteria:

• History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse, loss of consciousness, or incontinence)
• Participation in any interventional study for the treatment of food allergy in the past 6 months
• Known oat, wheat, or glycerin allergy
• Eosinophilic or other inflammatory (e.g. celiac) gastrointestinal disease
• Severe asthma (2007 NHLBI Criteria Steps 5 or 6 - Appendix 2)
• Inability to discontinue antihistamines for skin testing and DBPCFCs
• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year
• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
• Significant medical condition (e.g., liver, kidney, gastrointestinal, cardiovascular, hematologic, or pulmonary disease) which would make the subject unsuitable for induction of food reactions

• National Institute of Allergy and Infectious Diseases (NIAID)
• National Center for Complementary and Alternative Medicine (NCCAM)