Baked Milk Oral Immunotherapy for Cow's Milk Allergy

Cow's Milk Allergy Clinical Trial

Official title:

Phase II Study of Baked Milk Oral Immunotherapy for the Treatment of Cow's Milk Allergy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03462030
• Other study ID #: IRB00099590
• Status: Completed
• Phase: Phase 2
• Start date: March 15, 2018
• Est. completion date: February 19, 2024

Study information

• Verified date: February 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether baked milk oral immunotherapy is safe in the treatment of cow's milk allergy.

Description:

This study is designed to assess the safety of baked milk oral immunotherapy among patients who are milk allergic and who do not pass a baked milk challenge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: February 19, 2024
• Est. primary completion date: January 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

Inclusion Criteria:

• Patients who meet all of the following criteria are eligible for enrollment as study participants, including participants who:

• Are age 3-18 years, either sex, any ethnicity or race

• Provide signed informed consent by parent or legal guardian and informed assent if applicable

• Have a history of symptomatic reactivity to cow's milk (i.e. eczema, urticarial, upper or lower respiratory symptoms, gastrointestinal disturbances, rash, oral symptoms)

• Have a skin prick test positive to milk (diameter of wheal 3 mm = negative control) and serum milk-specific immunoglobulin E (IgE) level >5 kilo Units (kU)/L within the past 6-12 months

• Have a positive reaction to a cumulative dose of =444 mg of baked milk powder in the initial qualifying double blind placebo-controlled food challenge.

• Use an effective method of contraception by females of childbearing potential to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study.

• Have self-injectable epinephrine available at all times

Exclusion Criteria:

• Patients who meet any of these criteria are not eligible for enrollment as study participants, including participants who:

• Have a history of severe anaphylaxis resulting in hypotension, neurological compromise, or mechanical ventilation

• Have a history of intubation related to asthma

• Tolerate more than 444 mg of baked milk powder at the initial qualifying double blind placebo controlled food challenge.

• Allergy to placebo ingredients or reacts to any dose of placebo during the qualifying oral food challenge.

• Poor control of atopic dermatitis

• Are unable to tolerate at least 3 mg of baked milk protein on dose escalation day

• Are pregnant or lactating

• Have severe asthma defined by 2007 National Heart Lung and Blood Institute (NHLBI) Criteria Steps 5 or 6

• Have severe or poorly controlled asthma defined by with any of the following criteria:

1. Forced expiratory volume in 1 second (FEV1) <80% of predicted

2. Inhaled corticosteroid dosing dosing of >500 mcg daily of fluticasone (or equivalent inhaled corticosteroids based on NHLBI dosing chart) or

3. = 1 hospitalization in the past year for asthma or

4. > 1 emergency department visit in the past 6 months for asthma

• Use of steroid medications (oral steroids, such as prednisone or Medrol, steroid injections, such as Kenalog, or intravenous or oral corticosteroid burst) in the following manners: History of daily oral steroid dosing within 4 weeks prior to baseline visit or for > 1 month during the past year or >2 burst oral steroid courses in the past 6 months.

• Are unable to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or food challenges

• Are receiving omalizumab, mepolizumab, beta- blocker, angiotensin-converting-enzyme inhibitor (ACE-I), angiotensin-receptor blockers, calcium channel blockers, or tricyclic antidepressant therapy

• Have used immunomodulatory therapy (not including corticosteroids) or biologic therapy within the past year

• Have participated in any interventional study for treatment of a food allergy in the past 6 months

• Are on 'build up phase' of environmental allergen immunotherapy. Subjects tolerating maintenance allergen immunotherapy can be enrolled.

• Have a history of eosinophilic esophagitis in the past 3 years

• Have a chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes)

• Have used an investigational drug within 90 days or plan to use an investigational drug during the study period

• Severe reaction at initial double blind placebo controlled food challenge, defined as:

• Life-threatening anaphylaxis

• Requiring overnight hospitalization

Related Conditions & MeSH terms

• Cow's Milk Allergy
• Hypersensitivity
• Milk Hypersensitivity

Intervention

Drug:
• Baked non-fat cow's milk powder
Oral immunotherapy with increasing quantities of baked milk.
• Placebo: Tapioca Powder
Placebo control.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	La Jolla Institute for Allergy & Immunology, Myra Reinhardt Foundation

Country where clinical trial is conducted

United States, 

References & Publications (32)

Bernstein DI, Wanner M, Borish L, Liss GM; Immunotherapy Committee, American Academy of Allergy, Asthma and Immunology. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol. 2004 Jun;113(6):1129-36. doi: 10.1016/j.jaci.2004.02.006. — View Citation

Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. Nutr Res. 2011 Jan;31(1):61-75. doi: 10.1016/j.nutres.2011.01.001. No abstract available. — View Citation

Burbank AJ, Sood P, Vickery BP, Wood RA. Oral Immunotherapy for Food Allergy. Immunol Allergy Clin North Am. 2016 Feb;36(1):55-69. doi: 10.1016/j.iac.2015.08.007. — View Citation

Chafen JJ, Newberry SJ, Riedl MA, Bravata DM, Maglione M, Suttorp MJ, Sundaram V, Paige NM, Towfigh A, Hulley BJ, Shekelle PG. Diagnosing and managing common food allergies: a systematic review. JAMA. 2010 May 12;303(18):1848-56. doi: 10.1001/jama.2010.582. — View Citation

Cummings AJ, Knibb RC, King RM, Lucas JS. The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review. Allergy. 2010 Aug;65(8):933-45. doi: 10.1111/j.1398-9995.2010.02342.x. Epub 2010 Feb 22. — View Citation

Devenney I, Falth-Magnusson K. Skin prick tests may give generalized allergic reactions in infants. Ann Allergy Asthma Immunol. 2000 Dec;85(6 Pt 1):457-60. doi: 10.1016/S1081-1206(10)62571-9. — View Citation

Eigenmann PA, Caubet JC, Zamora SA. Continuing food-avoidance diets after negative food challenges. Pediatr Allergy Immunol. 2006 Dec;17(8):601-5. doi: 10.1111/j.1399-3038.2006.00455.x. — View Citation

Flokstra-de Blok BM, Dubois AE, Vlieg-Boerstra BJ, Oude Elberink JN, Raat H, DunnGalvin A, Hourihane JO, Duiverman EJ. Health-related quality of life of food allergic patients: comparison with the general population and other diseases. Allergy. 2010 Feb;65(2):238-44. doi: 10.1111/j.1398-9995.2009.02121.x. Epub 2009 Oct 1. — View Citation

Goldberg MR, Nachshon L, Appel MY, Elizur A, Levy MB, Eisenberg E, Sampson HA, Katz Y. Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J Allergy Clin Immunol. 2015 Dec;136(6):1601-1606. doi: 10.1016/j.jaci.2015.05.040. Epub 2015 Jul 17. — View Citation

Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, Holl JL. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011 Jul;128(1):e9-17. doi: 10.1542/peds.2011-0204. Epub 2011 Jun 20. — View Citation

Hobbs CB, Skinner AC, Burks AW, Vickery BP. Food allergies affect growth in children. J Allergy Clin Immunol Pract. 2015 Jan-Feb;3(1):133-4.e1. doi: 10.1016/j.jaip.2014.11.004. Epub 2014 Nov 25. — View Citation

Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, Kamilaris J, Burks AW. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009 Aug;124(2):286-91, 291.e1-6. doi: 10.1016/j.jaci.2009.03.045. Epub 2009 May 27. — View Citation

Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, Steele P, Driggers S, Burks AW, Wood RA. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012 Feb;129(2):448-55, 455.e1-5. doi: 10.1016/j.jaci.2011.10.023. Epub 2011 Nov 30. — View Citation

Kim J, Kwon J, Noh G, Lee SS. The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract. 2013 Dec;7(6):488-94. doi: 10.4162/nrp.2013.7.6.488. Epub 2013 Nov 29. — View Citation

Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA. Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol. 2011 Jul;128(1):125-131.e2. doi: 10.1016/j.jaci.2011.04.036. Epub 2011 May 23. — View Citation

Lin MS, Tanner E, Lynn J, Friday GA Jr. Nonfatal systemic allergic reactions induced by skin testing and immunotherapy. Ann Allergy. 1993 Dec;71(6):557-62. — View Citation

Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008 Feb;121(2):343-7. doi: 10.1016/j.jaci.2007.10.029. Epub 2007 Dec 26. — View Citation

Martorell A, De la Hoz B, Ibanez MD, Bone J, Terrados MS, Michavila A, Plaza AM, Alonso E, Garde J, Nevot S, Echeverria L, Santana C, Cerda JC, Escudero C, Guallar I, Piquer M, Zapatero L, Ferre L, Bracamonte T, Muriel A, Martinez MI, Felix R. Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy. Clin Exp Allergy. 2011 Sep;41(9):1297-304. doi: 10.1111/j.1365-2222.2011.03749.x. Epub 2011 Apr 11. — View Citation

Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004 Sep;59(9):980-7. doi: 10.1111/j.1398-9995.2004.00542.x. — View Citation

Narisety SD, Skripak JM, Steele P, Hamilton RG, Matsui EC, Burks AW, Wood RA. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow's milk allergy. J Allergy Clin Immunol. 2009 Sep;124(3):610-2. doi: 10.1016/j.jaci.2009.06.025. Epub 2009 Aug 8. — View Citation

Nelson HS, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):744-51. doi: 10.1016/s0091-6749(97)80006-1. — View Citation

Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol. 2008 Aug;122(2):342-7, 347.e1-2. doi: 10.1016/j.jaci.2008.05.043. Epub 2008 Jul 11. — View Citation

Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992 Aug;90(2):256-62. doi: 10.1016/0091-6749(92)90080-l. — View Citation

Pajno GB, Caminiti L, Ruggeri P, De Luca R, Vita D, La Rosa M, Passalacqua G. Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Ann Allergy Asthma Immunol. 2010 Nov;105(5):376-81. doi: 10.1016/j.anai.2010.03.015. Epub 2010 Jul 31. — View Citation

Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014 Feb;133(2):291-307; quiz 308. doi: 10.1016/j.jaci.2013.11.020. Epub 2013 Dec 31. — View Citation

Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol. 2007 Nov;120(5):1172-7. doi: 10.1016/j.jaci.2007.08.023. Epub 2007 Nov 1. — View Citation

Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec;122(6):1154-60. doi: 10.1016/j.jaci.2008.09.030. Epub 2008 Oct 25. — View Citation

Valyasevi MA, Maddox DE, Li JT. Systemic reactions to allergy skin tests. Ann Allergy Asthma Immunol. 1999 Aug;83(2):132-6. doi: 10.1016/S1081-1206(10)62624-5. — View Citation

Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, Plaut M, Sampson HA. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol. 2016 Apr;137(4):1103-1110.e11. doi: 10.1016/j.jaci.2015.10.005. Epub 2015 Nov 12. — View Citation

Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer DM, Henning AK, Mayer L, Burks AW, Grishin A, Stablein D, Sampson HA. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013 Mar;131(3):805-12. doi: 10.1016/j.jaci.2012.10.060. Epub 2012 Dec 28. — View Citation

Wood RA. Food allergen immunotherapy: Current status and prospects for the future. J Allergy Clin Immunol. 2016 Apr;137(4):973-982. doi: 10.1016/j.jaci.2016.01.001. — View Citation

Yeung JP, Kloda LA, McDevitt J, Ben-Shoshan M, Alizadehfar R. Oral immunotherapy for milk allergy. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD009542. doi: 10.1002/14651858.CD009542.pub2. — View Citation

* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	Adverse events will be recorded per CTCAE version 4.0. Events per dose on baked milk oral immunotherapy will be compared to adverse events per dose on placebo. Data will be collected over the first year of treatment. Analysis of cumulative adverse reactions per dose of oral immunotherapy or placebo will be performed at the end of year 1.	1 year
Secondary	Proportion of Subjects Who Are Able to Tolerate 4 Grams of Baked Milk Protein After One Year of Treatment	The investigators will perform baked milk challenges to 4044 mg of baked milk protein and calculate the proportion of subjects who tolerate 4 grams of baked milk protein after one year of baked milk oral immunotherapy. This measure reports the number of participants that were able to tolerate 4 grams of baked milk protein.	1 year
Secondary	Proportion of Subjects Who Are Able to Tolerate 2 Grams of Unheated Milk Protein After 2 Years of Treatment	The investigators will perform unheated milk challenges to up to 8000 mg of unheated milk protein and calculate the proportion of subjects who tolerate 2 grams of unheated milk protein after 2 years of treatment. This measure reports the number of participants that were able to tolerate 2 grams of unheated milk protein.	2 years
Secondary	Change in Maximum Tolerated Dose of Baked Milk	Change in maximum tolerated dose (milligrams) of baked milk from baseline to end of year 1 and end of year 2.	Baseline, 1 year and 2 years
Secondary	Change in Milk-specific IgE Level	Change in milk-specific immunoglobulin E (IgE) level measured in kU/L.	Baseline and up to year 4
Secondary	Change in Milk-specific IgG4 Level	Change in milk-specific immunoglobulin G4 (IgG4) level measured in mg/L.	Baseline and up to year 4
Secondary	Change in Milk Skin Prick Test Responses	Change in milk skin prick test responses measured as a change in wheal size in millimeters.	Baseline and up to year 4
Secondary	Change in Quality of Life as Assessed by the Food Allergy Questionnaire	The food allergy questionnaire has an overall score range of 0-6 with 6 indicating the worst quality of life.	Baseline and up to year 4