A Prospective, Controlled, Double Blind, Multi-Center, Randomized, 3 Arm, Phase 1b/2a Study to Assess the Safety, Tolerability, and Preliminary Efficacy of B244 Delivered as an Intranasal Spray in Healthy Volunteers and Subjects With Seasonal Allergic Rhinitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AOBiome LLC
- 入组人数
- 71
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
This is a Prospective, Controlled, Double Blinded, Single Center, Randomized, 3 Arm, Parallel Assignment, Phase 1b/2a Study to assess the safety, tolerability, and preliminary efficacy of B244 delivered as an intranasal spray in healthy volunteers and subjects with seasonal allergic rhinitis.
详细描述
This is a Prospective, Controlled, Double Blinded, Single Center, Randomized, 3 Arm, Parallel Assignment, Phase 1b/2a Study to assess the safety, tolerability, and preliminary efficacy of B244 delivered as an intranasal spray in healthy volunteers and subjects with seasonal allergic rhinitis. This will be a 2-part study. In Part 1, safety and tolerability will be evaluated during 14 days of study treatment twice-a-day followed by 4 weeks of follow-up in healthy volunteers. In Part 2, preliminary efficacy will be evaluated in subjects with a history of seasonal allergic rhinitis outside of the local pollen season.
For Part 1 (safety and tolerability evaluation in healthy volunteers) we will enroll 24 subjects. Safety and tolerability will be assessed by reporting of AEs, physical examination and vital signs (blood pressure, heart rate, respiratory rate) during 14 days of treatment and up to 28 days of follow-up.
An internal safety committee meeting will review the 2 week Part 1 safety data and, if there are no safety concerns, the study will proceed to Part 2 to evaluate preliminary efficacy in subjects with a history of seasonal allergic rhinitis (SAR)
For Part 2 (preliminary efficacy evaluation in subjects with a history of SAR to ragweed pollen) will enroll 42 subjects. Safety and tolerability will be assessed in subjects with allergic rhinitis by reporting of AEs, physical examination and vital signs (blood pressure, heart rate, respiratory rate) during 14 days of treatment.
For Part 2, study will be paused for safety review using the same stopping criteria as in Part 1.
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
This is a double blind study.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and Females, 18 to 65 years of age (committed to consistent use of an acceptable method of birth control as described in Section 10).
- •In good general health as determined by a thorough medical history and physical examination, and vital signs.
- •Nonsmoker or ex-smoker (stopped >1 year prior to study entry).
- •Subjects willing and able to provide written informed consent.
- •Is willing and able to comply with the requirements of the protocol and must be available for the full duration of the study.
- •For Part 1, subjects asymptomatic from any seasonal or perennial allergens.
- •For Part 1, elevated systolic blood pressure greater than 120 but less than 160 and never been on antihypertensive medications or have been off any hypertensive treatment for a period of 12 weeks or longer.
- •For Part 2, subjects with a well-documented history of seasonal allergic rhinitis (specifically ragweed pollen) with documentation of sensitivity by positive skin testing and/or IgE testing to the relevant allergens 12 months prior to enrollment that correlate with clinical history.
- •For Part 2, a ragweed positive skin prick test with a wheal diameter at least 5 mm larger than the negative control and/or a ragweed specific IgE greater or equal to 0.7 kU/L.
- •For Part 2, subjects with confounding allergies, or sensitization to cat epithelia, dog epithelia, Dermatophagoides farinae, or Dermatophagoides pteronyssinus or prevalent and relevant seasonal allergens as per the skin prick test may be included if sensitization is not clinically relevant (ie. subject is non-symptomatic and/or can avoid the allergen during the study) at the discretion of the Investigator.
- •For Part 2, subjects with a baseline TNSS ≤ 3/12 at Visit 3 and a minimum qualifying TNSS score of a change of 6/12 from their baseline score after NAC #1 on at least 2 diary cards.
- •For Part 2, subjects' average post diluents nasal congestion score must be < 1 at admission for each study visit.
排除标准
- •Pregnancy or breast-feeding
- •Female of childbearing potential not using adequate contraceptive measures.
- •Smoking within the past year or during the protocol.
- •Systemic corticosteroid or other immunosuppressive medications use in the previous three months or during the protocol.*
- •Intranasal corticosteroid use in the previous month or during the protocol.*
- •Intranasal antihistamine or cromolyn use in the previous week or during the study.*
- •Allergen immunotherapy during previous 12 months or during the protocol.*
- •Omalizumab use in previous 12 months or during the protocol.*
- •Systemic antihistamine or leukotriene modifying medication use in the previous week or during the protocol.*
- •Use of antibiotics, NSAIDS, antihypertensives, beta-blockers, photosensitizing medications, or vitamin D supplements during study.
- •Use of any intranasally administered over-the-counter product or nasal irrigation (e.g., neti pot) during study.
- •Inability to give informed consent.
- •Persistent asthma or any medical condition that in the opinion of the investigator may compromise the subject's ability to safely participate in the study.
- •Subjects with any significant clinical abnormalities which may interfere with study participation.
- •Prior use of AO+ Mist.
- •Subjects with immunodeficiencies, nasal lesions, nasal polyps, or sinus infections.
- •Use of an investigational drug within 30 days before screening Visit
- •* Exclusionary criterion due to 1) medication use as marker of persistent comorbid allergic or inflammatory condition that may increase subject risk with study participation, 2) potential of medication to interfere with study outcome measures or results.
结局指标
主要结局
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
时间窗: Baseline to Day 28
Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration for subjects only from Part 1 of the study.
次要结局
- Subjective Nasal Symptom Scores of Nasal Congestion After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Nasal Symptom-free Response Rate in Sneezing Scores After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Nasal Symptom-free Response Rate in Nasal Congestion Scores After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Nasal Symptom-free Response Rate in Rhinorrhea Scores After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Subjective Nasal Symptom Scores of Sneezing After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Change in Total Nasal Symptom Score (TNSS) After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Subjective Nasal Symptom Scores of Rhinorrhea After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Subjective Nasal Symptom Scores of Nasal Itching After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Nasal Symptom-free Response Rate in TNSS After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)
- Nasal Symptom-free Response Rate in Nasal Itching Scores After Prophylaxis Treatment(Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.)