A Phase 1 Study of Heat/Phenol-Killed, E. Coli-Encapsulated, Recombinant Modified Peanut Proteins Ara h 1, Ara h 2, and Ara h 3 (EMP 123) in Healthy Volunteers Followed by Subjects Allergic to Peanuts (CoFAR 1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Percentage of participants who successfully complete the dosage regimen with no more than mild symptoms related to EMP-123 dosing
研究概览
简要总结
The purpose of this study is to evaluate the safety and side effects of a study product that contains recombinant modified peanut proteins (EMP-123) in healthy and peanut-allergic participants. This is a first in human study.
As of November 2009, this study is no longer recruiting healthy volunteers and will only be recruiting individuals with peanut allergies.
详细描述
Peanut allergy is a common ailment in the United States. Research suggests that the prevalence of peanut allergy in the United States has doubled over the last 5 years. Currently, the only effective treatment for peanut allergy is a peanut-free diet and quick access to self-injectable epinephrine. This study will evaluate the safety of a rectally administered product, EMP-123, consisting of three recombinant modified peanut protein antigens encapsulated within dead E. coli. E. coli is a common bacterium found in everyone's colon. E. coli acts like a package to hold the modified peanut proteins. EMP-123 is designed to act as an allergy vaccine with an eventual goal to induce tolerance to the major peanut proteins responsible for peanut allergy.
This study will involve weekly dosing and for females, a pregnancy test will occur at 48 hours before the start of product administration and later during the study. The study will involve two steps. Step 1 will enroll 5 healthy participants who will receive four escalating doses of study product on a weekly basis. Participants will be monitored at the clinic for 2 hours after receiving each dose of study product. Each dosing visit will be followed with a phone interview to assess any adverse effects or symptoms. Participants in Step 1 will maintain a home diary and record any symptoms that occur between visits. After screening, Step 1 will consist of five study visits on Weeks 1, 2, 3, 4, and 8. Vital signs, adverse event monitoring, and review of the home diary will occur at all visits. Breathing tests will occur at most visits. Stool and urine collection will occur at Weeks 4 and 8. The expected duration of Step 1 is 8 weeks.
If no safety concerns are identified at the conclusion of Step 1, 10 peanut-allergic participants will be enrolled into the second phase of the study, Step 2.
Step 2 is expected to last 20 weeks. Participants in Step 2 will receive weekly dose escalation of the study product for 10 weeks followed by administration every 2 weeks for 6 weeks. Participants will remain in the clinic for 2 hours after every dose is received. Follow-up will then continue for 4 weeks after the conclusion of treatment. Each dosing visit will be followed with a phone interview to assess any adverse effects or symptoms. After screening, Step 2 will consist of 14 study visits. Vital signs, adverse event monitoring, and a review of the home diary will occur at all visits. Breathing tests will occur at most visits. A skin prick test and stool, blood, and urine collection will occur at select visits.
As of November 2009, this study is no longer recruiting healthy volunteers and will only be recruiting individuals with peanut allergies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Available for the duration of the trial
- •Ability to perform spirometry maneuvers
- •Agree to use effective methods of contraception for the duration of the study
- •For Step 1 participants, regular consumption of at least 5 grams of peanut at least twice per month during the last 6 months prior to study entry
- •For Step 2 participants, a convincing clinical history of peanut allergy and prick skin test positive to peanut. More information on these criteria can be found in the protocol.
排除标准
- •History of any severe anaphylaxis
- •Known allergy to hydroxypropyl methylcellulose, glycerol, or phenol
- •Evidence of clinically significant immunosuppressive neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease
- •Laboratory evidence of liver or hematologic disease. Pre-existing history of autoimmune or antibody mediated diseases. More information on this criterion can be found in the protocol.
- •Pre-existing history of autoimmune or antibody mediated diseases. More information on this criterion can be found in the protocol.
- •Any previous intubation due to allergies or asthma
- •History of ischemic cardiovascular disease
- •Uncontrolled hypertension
- •Significant medical condition that, in the opinion of the investigator, would interfere with the study
- •Chronic diarrhea
- •Inability to refrain from anal intercourse for the duration of the trial
- •Use of rectal medications during the study
- •Planned rectal procedures for the duration of the study
- •History of rectal surgery or bleeding in the last 6 months prior to study entry
- •History of proctitis in the last 6 months prior to study entry
- •History of inflammatory bowel disease, celiac disease, or eosinophilic esophagitis/gastroenteritis
- •Participation in another investigational vaccine or drug trial within 30 days prior to study or while the study is ongoing
- •Medical, occupational, or family problems as a result of alcohol or illicit drug use during the last 12 months prior to study entry
- •FEV1 value less than 80% predicted
- •Inability to discontinue antihistamines for skin testing
- •Currently on any allergy immunotherapy
- •Participation in any interventional study for the treatment of food allergy in the past 12 months prior to study entry
- •Poor control of persistent activation of atopic dermatitis
- •Use of omalizumab or other non-traditional forms of allergen immunotherapy or immunomodulatory therapy or biologic therapy within the past 12 months prior to study entry
- •Use of oral B-blockers, angiotensin-receptor blockers, or calcium channel blockers
- •Use of immunosuppressive drugs within 30 days prior to study entry or while study is ongoing
- •Use of corticosteroids within 30 days prior to study entry
- •Use of steroid medications. More information on this criterion can be found in the protocol.
- •History of serologic evidence of infection with HIV-1, HBV, or HCV
- •Receipt of blood products within the past 6 months prior to study entry
- •Inability to refrain from anal intercourse for the duration of the study
- •Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, would interfere with the study
- •Pregnant or breastfeeding
- •Step 1 participants:
- •History of any allergy to food, including peanut
- •Serum peanut-specific IgE greater than .35 kUa/L at screening
- •Prick skin test (PST) to peanut more than 3mm in diameter at screening
- •History of asthma
- •Step 2 participants:
- •More than mild persistent asthma as defined in the protocol.
- •Treatment for asthma, including: any hospitalization in the past year for asthma or any emergency room visit in the past 6 months for asthma.
结局指标
主要结局
Percentage of participants who successfully complete the dosage regimen with no more than mild symptoms related to EMP-123 dosing
时间窗: Throughout study
次要结局
- Occurrence of adverse events(Throughout study)
- Rate of desensitization, as determined by peanut endpoint titration prick test in peanut allergic participants(At pre- and post-treatment periods)
- Change in basophil activation(Throughout study)
- Decreased Type 2 helper T cell peanut-induced T-lymphocyte phenotype and increased T-lymphocyte regulatory phenotype(Throughout study)
- Increase in peanut-specific immunoglobulin (IgG4) and IgA(Throughout study)
- Decrease in peanut-specific IgE(Throughout study)