Phase 2 Randomized Controlled Trial Using Biologics to Improve Multi OIT Outcomes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 6
- 主要终点
- The success rates of passing a peanut Double-Blind Placebo Controlled Food Challenge (DBPCFC)
研究概览
简要总结
Food allergy is a serious public health concern that causes potentially-life threatening reactions in affected patients. The prevalence of food allergy in the United States (U.S.) has increased substantially and now affects 15 million patients:4-8% of children (6 million children, 30% with multiple food allergies) and about 9% of adults. This is a prospective Phase 2, multi-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be peanut. The intent-to-treat population in the clinical study will be 110 participants, ages 4 to 55 years with a history of multiple food allergies of 2 to 3 different foods including peanut. Allergy will be confirmed by food allergen (FA)-specific Immunoglobulin E (IgE) levels or positive Skin Prick Test (SPT). Enrolled participants must be positive during the Double-blind Placebo-controlled Food challenge (DBPCFC) at or before the 300 mg protein (444 mg cumulative) dosing level of FA proteins.
详细描述
This is a prospective Phase 2, multi-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be peanut. The total population will be 110 participants, ages 4 to 55 years that present with a history of multiple food allergies of 2 or 3 different foods including peanut, food-allergen (FA)-specific Immunoglobulin E (IgE) levels or positive Skin Prick Test (SPT).
Enrolled participants must react positively during DBPCFCs at or before the 300 mg (444 mg cumulative) dosing level of FA proteins of 2 or 3 allergens in which one must be a peanut.
There will be three study cohorts, all will be double-blinded:
Cohort A (50 participants) will be treated with omalizumab for 8 weeks followed by 24 weeks of treatment with placebo for dupilumab. Cohort B (50 participants) will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab. Cohort C (10 participants) will be treated with placebo for omalizumab for 8 weeks followed by 24 weeks treatment with dupilumab. All participants will receive multi-allergen OIT for peanut plus one or two additional protocol-specified foods from week 8 through week 32.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 4 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 4 through 55 years (inclusive).
- •Clinical history of peanut allergy and 1 or 2 additional foods from the following foods: milk, almond, shellfish, fish, cashew, hazelnut, egg, walnut, sesame seeds, soy, and wheat. Allergy to milk and egg is defined as unable to tolerate both cooked and uncooked forms.
- •Positive allergy test determined by:
- •ImmunoCAP serum IgE level >4 kilo Units of allergen per Liter (kUA/L) for each allergen within the past 12 months OR
- •Skin prick test (SPT) ≥6 mm wheal diameter to each allergen.
- •A clinical reaction during a DBPCFC to small doses of food defined as a cumulative dose of =/<444 mg food protein.
- •No clinical reaction observed during the placebo (oat) challenge.
- •Subject and/or parent guardian must be able to understand and provide informed consent.
- •Written informed consent from adult participants.
- •Written informed consent from parent/guardian for minor participants.
- •Written assent from minor participants as appropriate (e.g., at and above the age of 7 years).
- •Use of effective birth control by female participants of childbearing potential.
排除标准
- •History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension.
- •Individuals less than 15 kg in weight at start of the study
- •History of severe anaphylaxis to participant-specific foods that will be used in this study, defined as neurological compromise or requiring intubation.
- •History of chronic disease (other than asthma, atopic dermatitis or allergic rhinitis) that is, or is at significant risk of becoming, unstable or requiring a change in chronic therapeutic regimen.
- •History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), or recurrent gastrointestinal symptoms of undiagnosed etiology.
- •Severe asthma (NAEPP EPR-3 Medication Criteria Steps 5 or 6)
- •Mild or moderate asthma (NAEPP EPR-3 Medication Criteria Steps 1-4), if uncontrolled or difficult to control.
- •Uncontrolled asthma as evidenced by:
- •FEV1 < 80% of predicted, or ratio of Forced Expiratory Volume in 1 second (FEV1) to forced vital capacity (FEV1/ Forced Vital Capacity (FVC)) < 75% of predicted, with or without controller medications (only for age 6 or greater and able to do spirometry reliably. If unable to do spirometry, Peak Expiratory Flow (PEF) of >80% is acceptable) or;
- •One overnight admission to a hospital in the past year for asthma or;
- •Emergency room (ER) visit for asthma within six months prior to screening.
- •Inability to tolerate biological (antibody) therapies.
- •Use of immunomodulator therapy (not including corticosteroids).
- •Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers.
- •Current participation or within the last 4 months in any other interventional study.
- •Pregnancy or lactation.
- •Allergy to oat (placebo in DBPCFC).
- •Use of investigational drugs within 16 weeks of participation.
- •In build up phase of immunotherapy for aeroallergens or venom.
研究组 & 干预措施
Cohort A: Omalizumab
Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with placebo for dupilumab.
干预措施: Omalizumab (Drug)
Cohort B: Omalizumab/Dupilumab
Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.
干预措施: Omalizumab (Drug)
Cohort B: Omalizumab/Dupilumab
Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.
干预措施: Dupilumab (Drug)
Cohort C: Dupilumab
Participants will be treated with placebo for omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.
干预措施: Dupilumab (Drug)
结局指标
主要结局
The success rates of passing a peanut Double-Blind Placebo Controlled Food Challenge (DBPCFC)
时间窗: 44 weeks
Success is defined as passing a cumulative dose of \>=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B.
The success rates of passing a DBPCFC to peanut and at least one other FA
时间窗: 44 weeks
Success is defined as passing a cumulative dose of \>=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B.
The success rates of passing a DBPCFC to peanut and two other FAs
时间窗: 44 weeks
Success is defined as passing a cumulative dose of \>=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B.
次要结局
- Proportion of participants who pass DBPCFCs for each FA at a cumulative dose of ≥1,043 mg, ≥2,043 mg, or ≥4,043 mg at week 32 and/or week 44.(week 32 and/or 44)
- Proportion of participants who successfully pass DBPCFCs to a cumulative dose of >=1,043 mg protein to 1, 2, or 3 FAs when applicable at week 44(44 weeks)
- Proportion of participants who successfully pass DBPCFCs to a cumulative dose of ≥2,043 mg to 1, 2, or 3 FAs when applicable at week 32(32 weeks)
- Proportion of participants who have a 10-fold change in the cumulative tolerance dose for each FA at weeks 32 and/or week 44, compared to baseline(Baseline and week 32 and/or 44)
研究者
R. Sharon Chinthrajah
Medical Director, Clinical Research Unit
Stanford University