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Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants (OUtMATCH)

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ClinicalTrials.gov Identifier: NCT03881696
Recruitment Status : Recruiting
First Posted : March 19, 2019
Last Update Posted : November 30, 2020
Sponsor:
Collaborators:
Genentech, Inc.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE March 15, 2019
First Posted Date  ICMJE March 19, 2019
Last Update Posted Date November 30, 2020
Actual Study Start Date  ICMJE July 22, 2019
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
Number of Participants by Stage 1 Treatment Group, Omalizumab versus Placebo, Who Successfully Consume ≥600 mg of Peanut Protein Without Dose-Limiting Symptoms During the DBPCFC Conducted at the End of Treatment Stage 1 [ Time Frame: During the DBPCFC at the end of Stage 1: After 16 to 20 weeks of assigned Stage 1 treatment ]
Number of participants who successfully consume ≥600 mg of peanut protein without dose-limiting symptoms during the double-blind placebo-controlled oral food challenge (DBPCFC) conducted at the end of Stage 1 treatment. Dose-limiting symptoms are those that in the view of the principal investigator indicate a true allergic reaction.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants
Official Title  ICMJE Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy (OIT) in Food Allergic Children and Adults (CoFAR-11)
Brief Summary This study is a multi-center, randomized, double-blind, placebo-controlled study in participants 1 to less than 56 years of age who are allergic to peanut and at least two other foods (including milk, egg, wheat, cashew, hazelnut, or walnut). While each participant may be allergic to more than two other foods, the primary endpoint/outcome in this study will only be assessed in peanut and two other foods for each participant. The primary objective of the study is to compare the ability to consume foods without dose-limiting symptoms during a double-blind placebo-controlled food challenge (DBPCFC), after treatment with either omalizumab or placebo for omalizumab.
Detailed Description

Food allergy affects about 15 million people in the United States. This includes 6 million children. The current treatment for food allergy is to avoid eating the foods that may cause an allergic reaction and have medications such as epinephrine (adrenaline) in case of a reaction. However, accidental exposures can be extremely difficult to avoid, particularly if you are allergic to multiple foods. The risks of accidental exposures and life-threatening reactions can place a large burden on patients and their families.

Investigators in this study would like to learn if omalizumab injections alone or in combination with multi-allergen oral immunotherapy (OIT) will help people with multiple food allergies eat foods to which they are allergic. Oral means that you will take the food allergen (peanut and 2 other foods to which you are allergic) by mouth. If you are allergic to more than 3 foods, this study will only provide OIT for peanut and 2 other foods.

There are 3 stages to the study:

In Stage 1, investigators would like to learn:

• If omalizumab stops or decreases allergic reactions to peanut and other common food allergens after taking it for a length of time.

Stage 1 will also have an extra part so that 60 participants will receive omalizumab and everyone (the investigators conducting the research and study participants) will know it. This is why it is called the open label extension. This part of the study will assist investigators in learning if receiving omalizumab for a longer time may work better at decreasing allergic reactions.

In Stage 2, investigators would like to learn:

• How a short course of omalizumab combined with Multi-allergen OIT compares with a longer course of omalizumab in decreasing allergic reactions.

In Stage 3, investigators would like to learn:

• If, after participants stop both treatments, will they be able to eat the peanut and the 2 other foods in the form that is normally eaten.

In all stages, investigators would like to learn:

  • How safe and effective the treatments are and
  • How the OIT affects the immune system.

Participation will last up to 56 months (4 years and 8 months).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Peanut Allergy
  • Multi-food Allergy
Intervention  ICMJE
  • Drug: Omalizumab
    Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.
    Other Name: Xolair®
  • Drug: Placebo for Omalizumab
    Placebo contains the same ingredients as the omalizumab formulation, excluding omalizumab. Placebo will be supplied in pre-filled syringes (PFS). PFS of placebo will be provided to the clinical research units as 75 mg and 150 mg dosage forms.
    Other Name: Placebo
  • Drug: Multi-Allergen Oral Immunotherapy

    Multi-allergen OIT will be any of the following drug products: peanut, milk, egg, wheat, cashew, hazelnut, and walnut (all food protein flours).

    A prescription for each participant for the appropriate dose of each of the allergens will be prepared. The pharmacist will compound the appropriate allergens and dispense the Multi-allergen OIT dose in a blinded (masked) fashion. The Clinical Research Unit (CRU) staff will administer food flour to the participant orally in an age-appropriate food vehicle (e.g., applesauce, pudding, etc.). Dosage will be administered according to the study protocol.

    Other Name: Multi-Allergen OIT
  • Drug: Placebo for Multi-Allergen Oral Immunotherapy
    Oat flour will be used for placebo for Multi-allergen OIT. Route: by mouth/oral. Dosage will be administered according to the study protocol.
    Other Name: Placebo for Multi-Allergen OIT
  • Other: Double-Blind Placebo-Controlled Food Challenge Based Treatment

    Each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods. A treatment plan will include instructions for one of the following:

    • Long-term follow-up with dietary consumption of a food; or
    • Long-term follow-up with avoidance of a food; or
    • Rescue OIT for a food. The treatment plan for each food may change depending on a participant's response to prescribed treatment over time.
    Other Name: DBPCFC Based Treatment
Study Arms  ICMJE
  • Experimental: Stage 1:Omalizumab as Monotherapy

    Eligible participants are randomized to receive omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

    After 16 weeks of treatment, each participant will complete double-blind placebo-controlled food challenge (DBPCFCs) to each of their three specific foods to a cumulative dose of 6044 mg protein of each food.

    Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic.

    The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 Open Label Extension (OLE).All other participants who complete all four DBPCFCs will move Stage 2 of the study.

    Intervention: Drug: Omalizumab
  • Experimental: Stage 1: Omalizumab OLE

    OLE: Open Label Extension, Long-Term Treatment with Omalizumab. Participants will receive 24 weeks of open label omalizumab in accordance with the omalizumab dosing table defined in the study protocol. Omalizumab is administered by subcutaneous injection either every 2 weeks or every 4 weeks for 24 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

    After 24 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 8044 mg protein of each food. Each participant who completes all four DBPCFCs at the end of the Stage 1 OLE will move on to Stage 3 of the study.

    Throughout Stage 1 OLE, each participant will be instructed to strictly avoid all foods to which they are allergic.

    Intervention: Drug: Omalizumab
  • Placebo Comparator: Stage 1: Placebo for Omalizumab as Monotherapy

    Eligible participants are randomized to receive placebo for omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

    After 16 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 6044 mg protein of each food.

    Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic.

    The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 OLE. All other participants who complete all four DBPCFCs will move Stage 2 of the study.

    Intervention: Drug: Placebo for Omalizumab
  • Experimental: Stage 2: Omalizumab

    Participants will receive eight weeks of treatment with open label omalizumab in accordance with the omalizumab dosing table specified in the study protocol, administered by subcutaneous injection. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

    After completion of eight weeks of open label omalizumab, participants will be randomized 1:1 to either:

    • Omalizumab-facilitated oral immunotherapy (OIT): Open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks OR
    • Omalizumab + placebo OIT: Open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks.

    Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

    Intervention: Drug: Omalizumab
  • Experimental: Stage 2: Omalizumab-Facilitated OIT

    OIT: oral immunotherapy-Omalizumab as Adjunct Therapy to Multi-Allergen Oral Immunotherapy

    Participants randomized to open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks.

    Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

    Interventions:
    • Drug: Omalizumab
    • Drug: Multi-Allergen Oral Immunotherapy
  • Experimental: Stage 2: Omalizumab + Placebo OIT

    OIT: oral immunotherapy Participants randomized to open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks.

    Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

    Interventions:
    • Drug: Omalizumab
    • Drug: Placebo for Multi-Allergen Oral Immunotherapy
  • Stage 3: DBPCFC Based Treatment

    DBPCFC Based Treatment-Long-term Follow-up Treatment Plan for Peanut and Each of the Two Other Participant-Specific Foods.

    Upon completion of the DBPCFCs at the end of Stage 1 OLE or Stage 2, each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods based on the results of the DBPCFCs. A treatment plan will include instructions for one of the following:

    • Long-term follow-up with dietary consumption of a food;
    • Long-term follow-up with avoidance of a food; or
    • Rescue OIT for a food.

    The treatment plan for each food may change throughout Stage 3 depending on a participant's response to treatment. Once a participant enters Stage 3, the participant will remain in Stage 3 until December 2023.

    Note: Participants will be instructed to strictly avoid a food if they receive rescue OIT for the food during Stage 3.

    Intervention: Other: Double-Blind Placebo-Controlled Food Challenge Based Treatment
Publications * Sampson HA, Berin MC, Plaut M, Sicherer SH, Jones S, Burks AW, Lindblad R, Leung DYM, Wood RA. The Consortium for Food Allergy Research (CoFAR): The first generation. J Allergy Clin Immunol. 2019 Feb;143(2):486-493. doi: 10.1016/j.jaci.2018.12.989. Epub 2018 Dec 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 18, 2019)
225
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

  1. Participant and/or parent/legal guardian must be able to understand and provide informed consent and/or assent, as applicable;
  2. Peanut allergic: participant must meet all of the following criteria to minimize the chance that the participant will develop natural tolerance to peanut over the course of the study:

    1. Positive skin prick test (SPT) defined as ≥4 mm wheal greater than saline control) to peanut,
    2. Positive peanut immunoglobulin E (IgE), ≥6 kUA/L, at Screening or within three months of Screening, determined by ImmunoCap, and
    3. Positive double-blind placebo-controlled food challenge (DBPCFC), defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg of peanut protein.
  3. Allergic to at least two of the six other foods (milk, egg, wheat, cashew, hazelnut, walnut): each participant must meet all of the following criteria for at least two of the six other foods to minimize the chance that the participant will develop natural tolerance to at least two of the six other foods over the course of the study:

    1. Positive SPT (≥4 mm wheal) to food,
    2. Positive food specific IgE (≥6 kUA/L) at Screening or within three months of Screening, determined by ImmunoCap, and
    3. Positive DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg of food protein.
  4. With body weight (as measured at Screening) and total serum IgE level (as measured within three months of Screening) suitable for omalizumab dosing;
  5. If female of child-bearing potential, must have a negative urine or serum pregnancy test;
  6. For women of childbearing potential, must agree to,during the treatment period and for 60 days after the last dose of study drug:

    • remain abstinent (refrain from heterosexual intercourse), or
    • use acceptable contraceptive methods (barrier methods, or
    • oral, injected, or implanted hormonal methods of contraception, or
    • other forms of hormonal contraception that have comparable efficacy).
  7. Plan to remain in the study area of an OUtMATCH clinical research unit (CRU) during the trial; and
  8. Be willing to be trained on the proper use of an epinephrine autoinjector for the duration of the study.

Exclusion Criteria:

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

  1. Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent or comply with the study protocol;
  2. Clinically significant laboratory abnormalities at Screening;
  3. Dose-limiting symptoms to the placebo portion of the Screening DBPCFC;
  4. Sensitivity or suspected/known allergy to any ingredients (including excipients) of the

    • active or placebo oral food challenge (OFC) material,
    • multi-allergen oral immunotherapy (OIT), or
    • drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma globulin).

      • Note: Guidance for determination of sensitivity to excipients will be detailed in the study's Manual of Procedures (MOP).
  5. Poorly controlled atopic dermatitis (AD) at Screening, per the Principal Investigator's PI's) discretion;
  6. Poorly controlled or severe asthma/wheezing at Screening, defined by at least one of the following criteria:

    1. Global Initiative for Asthma (GINA) criteria regarding asthma control latest guidelines,
    2. History of two or more systemic corticosteroid courses within six months of Screening or one course of systemic corticosteroids within three months of Screening to treat asthma/wheezing,
    3. Prior intubation/mechanical ventilation for asthma/wheezing,
    4. One hospitalization or Emergency Department (ED) visit for asthma/wheezing within six months of Screening,
    5. Forced expiratory volume in one second (FEV1) <80 percent of predicted or FEV1/forced vital capacity (FVC) <75 percent, with or without controller medications (only for participants who are aged seven years or older and are able to perform spirometry), or
    6. Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (or equivalent ICS based on the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) dosing chart).
  7. History of severe anaphylaxis to participant-specific foods that will be used in this study, defined as neurological compromise or requiring intubation;
  8. Treatment with a burst of oral, intramuscular (IM), or intravenous (IV) steroids of more than two days for an indication other than asthma/wheezing within 30 days of Screening;
  9. Currently receiving oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants, or beta-blockers (oral or topical);
  10. Past or current history of eosinophilic gastrointestinal (GI) disease within three years of Screening;
  11. Past or current history of cancer, or currently being investigated for possible cancer;
  12. Previous adverse reaction to omalizumab;
  13. Past or current history of any immunotherapy to any of the foods being treated in this study (e.g., OIT, sublingual immunotherapy [SLIT], EPIT) within 6 months of Screening;
  14. Treatment with monoclonal antibody therapy, such as omalizumab (Xolair®), dupilumab (Dupixent®), benralizumab (Fasenra™), mepolizumab (Nucala®), reslizumab (Cinqair®), or other immunomodulatory therapy within six months of Screening;
  15. Currently on "build-up phase" of inhalant allergen immunotherapy (i.e., has not reached maintenance dosing). Note: Individuals tolerating maintenance allergen immunotherapy can be enrolled;
  16. Inability to discontinue antihistamines for the minimum wash-out periods required for SPTs,or OFCs;
  17. Current participation in another therapeutic or interventional clinical trial or participation within 90 days of Screening;
  18. Use of investigational drugs within 24 weeks of Screening;
  19. Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the last dose of omalizumab or placebo for omalizumab;
  20. Has a first-degree relative already enrolled in the study; or
  21. Past or current medical problems (e.g., severe latex allergy), history of other chronic diseases (other than asthma/wheezing, AD, or rhinitis) requiring therapy (e.g., heart disease, diabetes), findings from physical assessment, or abnormalities in clinical laboratory testing that are not listed above, which, in the opinion of the PI, may:

    • pose additional risks from participation in the study,
    • may interfere with the participant's ability to comply with study requirements, or
    • may impact the quality or interpretation of the data obtained from the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 55 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03881696
Other Study ID Numbers  ICMJE DAIT CoFAR-11
CoFAR-11 ( Other Identifier: Consortium for Food Allergy Research )
NIAID CRMS ID#: 38625 ( Other Identifier: DAIT NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Genentech, Inc.
  • Novartis Pharmaceuticals
Investigators  ICMJE
Study Chair: Robert A. Wood, MD Department of Pediatrics at the Johns Hopkins University School of Medicine
Study Chair: Sharon Chinthrajah, MD Department of Medicine, Stanford University School of Medicine
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP