Single Center, Placebo Controlled Clinical Study in Desensitization vs Tolerance Induction in Peanut Allergy Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Passing the Week 117 DBPCFC to Peanut
研究概览
简要总结
Determine whether peanut oral immunotherapy (OIT) induces clinical tolerance as assessed after the initial 3 month avoidance period
Secondary Objectives:
- Identify the basic immune mechanisms which can explain the differences in the effects of OIT in desensitized vs. tolerant individuals.
- Determine whether immune monitoring measurements reflecting underlying mechanisms during OIT can be used to predict responses to OIT in individual subjects and, ultimately, to improve the safety and efficacy outcomes in peanut OIT protocols.
详细描述
All arms will undergo an Initial Dose Escalation (IDE) Day and updosing regimen with a maintenance phase of OIT or placebo to a maximum of 4,000 mg protein daily, as peanut flour, in the OIT groups, and to a maximum of an equivalent amount of oat flour for the placebo group. After maintenance is achieved, all subjects will begin performing DBPCFCs (staged so as to ensure safety) at Week 104 and every 13 weeks thereafter. At Week 104, individuals that reach criteria will, based on the randomization that was done at the start of the study, either stop therapy with peanut and be switched to oat flour, or will be maintained on 300 mg peanut protein per day and all placebo subjects will decrease to the equivalent volume of oat flour (approximately 600 mg oat flour) to optimize the blind. All subjects will be evaluated every 13 weeks thereafter with DBPCFCs until the end of study.
Individuals in Arm A will be defined as "clinically tolerant" if there is no clinical reactivity at the Week 104 and Week 117 DBPCFC. Clinical reactivity is defined as any reaction ≥ Grade 1 based on the Bock's Criteria. Individuals in Arm A who meet the definition of "clinically tolerant" will continue to avoid peanut protein (i.e. continue on 600 mg per day of oat flour) as long as each subsequent DBPCFC (performed every 13 weeks until end of study) shows no clinical reactivity.
Individuals in Arm B will be defined as "desensitized" to a minimum of 300 mg per day of peanut protein if they show no clinical reactivity at DBPCFCs (week 117 to end of study).
Individuals in Arm C will be defined as "natural loss of responsiveness" if they show no clinical reactivity at DBPCFCs (week 117 to end of study).
We plan to identify the basic immune mechanisms which can explain the differences in the effects of OIT in individuals who do or do not become clinically tolerant and to determine whether immune monitoring can predict the safety and efficacy outcomes in peanut OIT protocols.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 7 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject and/or parent guardian must be able to understand and provide informed consent and/or assent as applicable.
- •Peanut-allergic subjects between the ages of 7-55 years old.
- •Sensitivity to peanut allergen as documented by a positive skin prick test result (5 mm or greater diameter wheal relative to negative control) within 10 months preceding enrollment.
- •Allergy to peanut based on a double-blind placebo-controlled oral food challenge (DBPCFC) (see Appendix 4 for scoring details) failed at a dose ≤500 mg with peanut protein within 10 months preceding enrollment.
- •All female subjects of child-bearing potential will be required to provide a blood or urine sample for pregnancy testing that must be negative one week before being allowed to participate in the study.
- •Subjects must plan to remain in the study area during the trial.
- •Subjects must be trained on the proper use of the EpiPen (see Appendix 6) to be allowed to enroll in the study.
- •Subjects with other food allergies must agree to eliminate these other food items from their diet so as not to confound the safety and efficacy data from the study.
- •Use of birth control by female subjects of child-bearing potential
排除标准
- •Inability or unwillingness of a participant to give written informed consent or comply with study protocol
- •History of cardiovascular disease
- •History of other chronic disease (other than asthma, atopic dermatitis, or rhinitis) requiring therapy (e.g., heart disease, diabetes) that, in the opinion of the Principal Investigator, would represent a risk to the subject's health or safety in this study or the subject's ability to comply with the study protocol
- •History of eosinophilic gastrointestinal disease
- •Current participation in any other interventional study
- •Subject is on 'build-up phase" of immunotherapy to another allergen (i.e., has not reached maintenance dosing)
- •Severe asthma (2007 NHLBI Criteria Steps 5 or 6) at time of enrollment
- •• Use of complementary and alternative medicine (CAM) treatment modalities (e.g., herbal remedies) for atopic and/or non-atopic disease within 90 days preceding Initial Dose Escalation Day (IDED) or at any time after the IDED
- •Inability to discontinue antihistamines for the initial day of escalation, skin testing or OFCs
- •Use of omalizumab within the past six months, or current use of other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids)
- •Use of β-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
- •Pregnancy or lactation
- •History of sensitivity to oat
- •History of severe anaphylaxis to peanut with symptoms including hypotension requiring fluid resuscitation and/or the need for mechanical ventilation
- •Use of investigational drugs within 24 weeks of participation
- •Past or current medical problems or findings from physical assessment or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
研究组 & 干预措施
Oat Flour 600 mg
Arm C that is maintained on placebo (oat flour) throughout the study; this arm will receive 600 mg oat flour beginning on week 104. This will be true even if a subject in the placebo group meets criteria at week 104
干预措施: Oat Flour (Drug)
Peanut Protein 4,000mg
Arm A on peanut OIT until week 104 (maintenance) and once meeting criteria [i.e. 1) on OIT treatment for minimum 104 weeks, 2) taking daily maintenance dose of 4,000 mg protein for at least 13 weeks, 3) no severe reactions to home dosing from Week 91-Week 104, and 4) no reactions at the Week 104 DBPCFC] will be assigned to avoid peanut (i.e. will consume 600 mg oat flour daily) and will proceed to tolerance and desensitization phase.
干预措施: Peanut Protein 4,000mg (Drug)
Peanut Protein 4,000mg
Arm A on peanut OIT until week 104 (maintenance) and once meeting criteria [i.e. 1) on OIT treatment for minimum 104 weeks, 2) taking daily maintenance dose of 4,000 mg protein for at least 13 weeks, 3) no severe reactions to home dosing from Week 91-Week 104, and 4) no reactions at the Week 104 DBPCFC] will be assigned to avoid peanut (i.e. will consume 600 mg oat flour daily) and will proceed to tolerance and desensitization phase.
干预措施: Oat Flour (Drug)
Peanut Protein 300 mg
Arm B on peanut OIT until week 104 and once meeting criteria specified in description of Arm A, will be assigned to be maintained on 300 mg peanut protein (i.e. 600 mg peanut flour) daily and will proceed to the tolerance and desensitization testing phase.
干预措施: Oat Flour (Drug)
Peanut Protein 300 mg
Arm B on peanut OIT until week 104 and once meeting criteria specified in description of Arm A, will be assigned to be maintained on 300 mg peanut protein (i.e. 600 mg peanut flour) daily and will proceed to the tolerance and desensitization testing phase.
干预措施: Peanut Protein 300 mg (Drug)
结局指标
主要结局
Passing the Week 117 DBPCFC to Peanut
时间窗: Week 117 - Number of participants with no clinical reactivity to peanuts
Number of Participants with No Clinical Reactivity to Peanuts
次要结局
- Passing the DBPCFC to Peanut at Week 130(Week 130)
研究者
Kari Christine Nadeau, MD PhD
Principal Investigator
Stanford University