A Phase I/II Trial in 3 Parts Assessing the Safety, Tolerability, and Efficacy of a Once-daily Peanut Sublingual Immunotherapy (SLIT) Tablet in Adults, Adolescents, and Children With Peanut Allergy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 209
- 试验地点
- 78
- 主要终点
- Part 1 and 2: Dose tolerability response rate
研究概览
简要总结
This clinical research study investigates the safety, tolerability and efficacy of a peanut SLIT-tablet in adults, adolescents, and children with peanut allergy.
详细描述
This is a phase I/II, dose-escalation, multi-site trial including subjects with peanut allergy confirmed by screening double-blind, placebo-controlled food challenge. The trial is conducted in 3 parts; part 1 will determine the entry dose of the up-dosing regimen (UDR) in adults and adolescents; part 2 will characterize the tolerability of the up-dosing regimen in adults, adolescents and children; part 3 will evaluate the efficacy of 2 maintenance doses of the SLIT-tablet primarily in adolescents and children; a small number of adults may also be included.
Peanut SLIT tablets administered as 9 doses covering a 4000-fold increase in dose will be used in the study.
In part 1, subjects will receive a peanut SLIT-tablet with one of five doses once daily for 2 weeks.
In part 2, subjects will receive a series of increasing doses of the peanut SLIT-tablet, where each dose is taken once daily for 2 weeks. The entry dose for the up-dosing regimen will be determined from part 1.
In part 3, subjects will be randomized into 3 treatment groups (UDR and Maintenance A, UDR and Maintenance B, Placebo UDR and Placebo). Subjects will receive a series of increasing doses of the peanut SLIT-tablet , where each dose is taken once daily for 2 weeks, followed by Maintenance A or B once daily for 24 weeks; or the corresponding Placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 and 2 is open label. Part 3 is blinded.
入排标准
- 年龄范围
- 4 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects are eligible to be included in the trial only if all the following criteria apply:
- •Part 1: Male or female aged 12 through 65 years (inclusive) on the day of enrollment Part 2: Male or female aged 4 through 65 years (inclusive) on the day of enrollment Part 3: Male or female aged 4 through 65 years (inclusive) on the day of randomization
- •Documented clinical history of an IgE-mediated allergic reaction towards peanut- containing food
- •Peanut-specific serum IgE ≥ 0.7 kU/L at screening measured at central laboratory
- •Skin prick test to peanut ≥ 5 mm at screening
- •Cohorts 1-8: Experience dose-limiting symptoms at the 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC Cohorts 9-10: Experience dose-limiting symptoms at the 1 mg or 3 mg challenge dose of peanut protein on the screening DBPCFC Part 3: Experience dose-limiting symptoms at the 3 mg, 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC
排除标准
- •Subjects are excluded from the trial if any of the following criteria apply:
- •Diagnosis or history of eosinophilic esophagitis
- •Uncontrolled asthma as defined by the Asthma Control Test questionnaire with a score of 19 or below at enrollment (subjects with a diagnosis of asthma only)
- •All subjects ≥ 5 years old with FEV1 or PEFR < 70% of predicted value at enrollment Subjects 4 years old with a history of recurrent wheeze requiring inhaled corticosteroids for 2 consecutive weeks or more within 3 months prior to enrollment
- •Up-dosing with any allergy immunotherapy product. Maintenance dose of any subcutaneous immunotherapy product other than peanut is allowed
- •History of peanut oral immunotherapy within the last 12 months prior to visit 1
- •Chronic or acute oral inflammation at enrollment
- •History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
- •Currently using any prohibited medication on the list of prohibited medication
- •Part 1 and 2: Allergic symptoms in reaction to the placebo part of the screening DBPCFC Part 3: Dose-limiting allergic symptoms in reaction to the placebo part of the screening DBPCFC
- •History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of the screening DBPCFC
- •Part 1 and 2: Asthma according to below criteria:
- •Severe asthma as per the current GINA guidelines
- •Uncontrolled or poorly controlled asthma as per the current GINA guidelines
- •Asthma that requires more than a daily dose above 800 µg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
- •History of 2 or more systemic corticosteroid courses within 6 months of screening
- •Prior intubation/mechanical ventilation for asthma
- •Emergency room visit or hospitalization for asthma in the 12 months prior to screening
- •Any history of a life-threatening asthma attack
- •Part 3: Asthma fulfilling the below criteria:
- •History of 2 or more systemic corticosteroid courses within 6 months of screening
- •Prior intubation/mechanical ventilation for asthma
- •Emergency room visit or hospitalization for asthma in the 12 months prior to screening
- •Any history of a life-threatening asthma attack
- •(US only) Severe asthma as per the current GINA guidelines
- •(US only) Uncontrolled or poorly controlled asthma as per the current GINA guidelines
- •(US only) Asthma that requires more than a daily maintenance dose above 800 μg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
研究组 & 干预措施
Part 1: Cohort 5
Adults and adolescents - peanut SLIT-tablet once daily for 2 weeks
干预措施: Peanut SLIT-tablet (Biological)
Part 2: Cohort 6
Adults - UDR with once daily peanut SLIT-tablet
干预措施: Peanut SLIT-tablet (Biological)
Part 2: Cohort 9
Highly sensitized Adults/Adolescents - UDR with once daily peanut SLIT-tablet
干预措施: Peanut SLIT-tablet (Biological)
Part 1: Cohort 1
Adults and adolescents - peanut SLIT-tablet once daily for 2 weeks
干预措施: Peanut SLIT-tablet (Biological)
Part 1: Cohort 2
Adults and adolescents - peanut SLIT-tablet once daily for 2 weeks
干预措施: Peanut SLIT-tablet (Biological)
Part 3: Placebo
Placebo UDR + placebo maintenance
干预措施: Placebo (Other)
Part 2: Cohort 10
Highly sensitized Children - UDR with once daily peanut SLIT-tablet
干预措施: Peanut SLIT-tablet (Biological)
Part 1: Cohort 3
Adults and adolescents - peanut SLIT-tablet once daily for 2 weeks
干预措施: Peanut SLIT-tablet (Biological)
Part 2: Cohort 7
Adolescents - UDR with once daily peanut SLIT-tablet
干预措施: Peanut SLIT-tablet (Biological)
Part 1: Cohort 4
Adults and adolescents - peanut SLIT-tablet once daily for 2 weeks
干预措施: Peanut SLIT-tablet (Biological)
Part 2: Cohort 8
Children - UDR with once daily peanut SLIT-tablet
干预措施: Peanut SLIT-tablet (Biological)
Part 3: Maintenance A
UDR A + maintenance dose A
干预措施: Peanut SLIT-tablet (Biological)
Part 3: Maintenance B
UDR B + maintenance dose B
干预措施: Peanut SLIT-tablet (Biological)
结局指标
主要结局
Part 1 and 2: Dose tolerability response rate
时间窗: 2 weeks per dose
The dose tolerability response rate is defined as the percentage of subjects who experience at most moderate local application site reactions after the last peanut SLIT-tablet intake of the dose step. Local application site reactions are treatment-related adverse events occurring in close proximity to the application site of the SLIT-tablet with a temporal relationship to tablet administration.
Part 3: TD-600 response rate
时间窗: After 24 weeks of maintenance treatment, up to 48 weeks.
The TD (tolerated dose)-600 response rate is defined as the percentage of subjects able to consume 600 mg (1044 mg cumulative) peanut protein without dose-limiting symptoms at the exit double-blind placebo-controlled food challenge (DBPCFC) after 24 weeks of maintenance treatment. Subjects that do not complete the exit DBPCFC are classified as non-responders.
次要结局
- Part 1, 2 and 3: Treatment-emergent adverse events(Part 1 and 2: 2 weeks per dose; Part 3: from first IMP intake to 7 days after last IMP intake, up to 48 weeks.)
- Part 3: TD-300 response rate(After 24 weeks of maintenance treatment, up to 48 weeks.)
- Part 3: TD-1000 response rate(After 24 weeks of maintenance treatment, up to 48 weeks.)
- Part 3: TD-2000 response rate(After 24 weeks of maintenance treatment, up to 48 weeks.)
- Part 3: Maximum tolerated dose of peanut protein during DBPCFC(At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks.)
- Part 3: Maximum severity of symptoms at each challenge dose of peanut protein during DBPCFC(At screening, 1 - 3 weeks, and after 24 weeks of maintenance treatment, up to 48 weeks.)
- Part 3: Response rate - use of epinephrine as rescue medication during exit DBPCFC(After 24 weeks of maintenance treatment, up to 48 weeks.)