Cockroach Nasal Allergen Challenge Pilot

Study Overview
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Brief Summary
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This research is being done to look at the body's response to cockroach extract, an allergen, when sprayed into the nose. The spraying of the cockroach extract into the participant's nose is called Nasal Allergen Challenge (NAC). The purpose of this study is to evaluate the safety and tolerability of a intranasal cockroach extract given to participants with asthma.

Detailed Description
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This is a multi-center, open label pilot study to assess the safety and determine the feasibility of cockroach nasal allergen challenge in children with asthma. This pilot study will occur in two phases: Phase 1 will enroll 10 cockroach sensitive adults with asthma who will undergo a nasal allergen challenge with increasing doses of cockroach allergen. Phase 1 will consist of two parts, Phase 1a and Phase 1b. In Phase 1a, participants will undergo a nasal allergen challenge. In Phase 1b, participants will undergo a repeat nasal allergen challenge to assess reproducibility of the NAC with cockroach allergen in a population with asthma. The data from Phase 1a will be used to identify a range of doses that is safe and elicits a threshold of nasal symptoms (TNSS ≥8). Phase 2 will enroll 25 cockroach sensitive children with asthma ages 8-14 years who will undergo a nasal allergen challenge using the dose range identified in Phase 1a. Study mandated procedures include: blood draws (venipuncture); pulmonary function testing (PFTs); nasal allergen challenge (NAC); allergen skin testing; and peak expiratory flow.

Official Title
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A Pilot Study to Assess Safety and Feasibility of Cockroach Nasal Allergen Challenge in Cockroach Sensitive Children and Adults With Asthma (ICAC-27)

Conditions
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Asthma, Cockroach Hypersensitivity

Intervention / Treatment
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* Biological: Glycerinated German Cockroach Allergenic Extract


Participation Criteria
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Eligibility Criteria
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Accrual Objective: N=10 adults, 25 children) STUDY INCLUSION CRITERIA: Subjects fulfilling all of the following criteria are eligible for enrollment as study participants for Phase 1a and Phase 2: Subject and/or parent guardian must be able to understand and provide informed consent. Male or female adults, 18 through 55 years of age at recruitment (Phase 1) or male or female children, 8-14 years of age at recruitment (Phase 2). Have a history of asthma for a minimum of 1 year before study entry: A diagnosis of asthma for this study is defined as a reported clinical diagnosis of asthma made by a physician over a year ago. The subject must have persistent asthma defined by the current need for at least 100 microgram (mcg) fluticasone per day or the equivalent of another inhaled corticosteroid. The subject's asthma must be well controlled as defined by: A Forced Expiratory Volume in 1 Second (FEV1) ≥ 80% predicted. An Asthma Control Test (ACT) score ≥ 20. Are sensitive to German Cockroach as documented by a positive (≥ 3 mm greater than negative control) skin prick test result and a positive German Cockroach specific immunoglobulin E (IgE) (≥0.35 kUA/L). Have no known contraindications to the allergenic extracts or diluents. Subjects who meet the following criteria are eligible for enrollment as study participants in Phase 1b after completion of Phase 1a: Their asthma must be well controlled as defined by: A FEV1 ≥ 80% predicted. An Asthma Control Test (ACT) score ≥ 20. The subject tolerated the Nasal Allergen Challenge (NAC) during Phase 1a with no adverse events grade 2 or higher as determined by Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (published September 2007) for local reactions to study procedures. Subjects not eligible for enrollment as study participants in Phase 1b after completion of Phase 1a if any of the following criteria are met: Are pregnant or lactating. Have an asthma severity classification of severe persistent, using the NAEPP classification, as evidenced by at least one of the following: Require a dose of greater than 500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid. Have received more than 2 courses of oral or parenteral corticosteroids within the last 12 months or one course within the last 3 months. Have been treated with depot corticosteroids within the last 12 months. Have been hospitalized for asthma within the 12 months prior to their participation in Phase1b. Have had an emergency room visit for asthma within the 3 months prior to their participation in Phase 1b. Have had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to their participation in Phase 1b. Have received allergen immunotherapy (SLIT or SCIT) in the last 12 months prior to their participation in Phase 1b. Have previously been treated with anti-IgE therapy in the 12 months prior to their participation in Phase 1b. Are currently receiving oral or nasal antihistamines, nasal corticosteroids, nasal decongestants, nasal anticholinergics or cromolyn, which cannot be suspended for the required washout periods prior to the nasal allergen challenge in Phase 1b. Have received an investigational drug in the 30 days prior to their participation in Phase 1b. Have past or current medical problems or findings from physical examination 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 subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. Meet any of the Participant Stopping Rules and Withdrawal Criteria during Phase 1a The participant elected to withdraw consent from all future study activities, including followup. The Investigator no longer believes participation is in the best interest of the participant. Serious Adverse Event (SAE) related to investigational product. Anaphylactic reaction grade 2 or 3. Inability to tolerate the NAC prior to reaching a TNSS ≥8 due to excessive discomfort or symptoms. Epistaxis occurring during the Challenge Visit. The need to start immunotherapy or any chronic immunosuppressive medications in the period between Phase 1a and Phase 1b. Require a dose of greater than 500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid to maintain asthma control in the period between Phase 1a and Phase 1b. Inability to restrict use of antihistamines, nasal steroids, nasal decongestants, nasal anticholinergics or cromolyn prior to the NAC. Development of any serious medical illness whose natural history, sequela, or treatment would be worsened or impaired by continuation in the protocol. Subject is lost to follow-up The subject's initial TNSS at the Repeat Challenge Visit must be within 1 point of the initial TNSS at the Challenge Visit in Phase 1a. If the participant's initial TNSS is outside the 1 point range, then the participant may be reevaluated for the Repeat Challenge Visit up to 3 additional times. STUDY EXCLUSION CRITERIA: Subjects fulfilling any of the following criteria are not eligible for enrollment in any portion of the study and may not be reassessed. Participants are ineligible if they: Plan to move from the area during the study period. Have a history of idiopathic anaphylaxis or anaphylaxis grade 2 or higher as defined by the grading scale of Brown et al. for anaphylaxis and systemic reactions to study procedures. Have unstable angina, significant arrhythmia, uncontrolled hypertension, history of autoimmune disease, or other chronic or immunological diseases that in the opinion of the investigator might interfere with the evaluation of the investigational agent or pose additional risk to the participant. Are using tricyclic antidepressants or beta-adrenergic blocker drugs (both oral and topical). EXCLUSION CRITERIA SPECIFIC TO STUDY PHASE 1A AND -2: Subjects who meet any of these criteria are not eligible for enrollment as study participants in Phase1a and Phase 2: Are pregnant or lactating. Post-menarcheal females must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral, subcutaneous, mechanical, or surgical contraception). Cannot perform spirometry at Screening. Have an asthma severity classification at Recruitment of severe persistent, using the The National Asthma Education and Prevention Program (NAEPP) classification, as evidenced by at least one of the following: Require a dose of greater than 500mcg of fluticasone per day or the equivalent of another inhaled corticosteroid. Have received more than 2 courses of oral or parenteral corticosteroids within the last 12 months or one course within the last 3 months. Have been treated with depot corticosteroids within the last 12 months. Have been hospitalized for asthma within the 12 months prior to recruitment. Have had an emergency room visit for asthma within the 3 months prior to recruitment. Have had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to recruitment. Have nasal polyps or other major structural abnormalities in their nasal cavities as assessed by anterior rhinoscopy. Have active rhinitis symptoms prior to the nasal allergen challenge, defined as a Baseline Total Nasal Symptom Score(TNSS) >3,with no individual symptom score >1. Do not have access to a phone (needed for scheduling appointments). Have received allergen immunotherapy (Sublingual [SLIT] or Subcutaneous [SCIT]) in the last 12 months prior to recruitment or who plan to initiate or resume allergen immunotherapy during the study. Have previously been treated with anti-IgE therapy in the 12 months prior to recruitment. Are currently receiving oral or nasal antihistamines, nasal corticosteroids, nasal decongestants,nasal anticholinergics or cromolyn, which cannot be suspended for the required washout periods prior to skin prick testing and the nasal allergen challenge. Have received an investigational drug in the 30 days prior to recruitment or who plan to use an investigational drug during the study. Past or current medical problems or findings from physical examination 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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glycerinated CR Allergenic Extract<br>Complete Arm Title: Glycerinated German Cockroach Allergenic Extract. Cockroach sensitive subjects are exposed to cockroach nasal allergen (NAC) intranasally at at increasing doses per protocol. The NAC aim is pursuit of optimal dose range as determined by tolerability and eliciting a threshold of nasal symptoms. | Biological: Glycerinated German Cockroach Allergenic Extract<br>* Participants will receive escalating doses intranasally. Briefly: per protocol- Phase 1a NAC: N=10 cockroach sensitive adults with asthma will undergo nasal allergen challenge with dose escalation (up to 8 doses per protocol). Phase 1b: Phase 1a subjects will have repeat NAC with dose escalation (up to 8 doses). Phase 2: N=25 cockroach sensitive children with asthma (ages 8 - 14 years) will undergo NAC with doses determined by Phase 1a data (e.g., symptoms and safety data).<br>* Other names: Cockroach antigen (CR antigen);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Proportion of Participants Meeting Either a Total Nasal Symptom Score (TNSS) Threshold or Sneezing Score Threshold During the Cockroach Allergen (CA) Nasal Allergen Challenge (NAC) | Result is the proportion of participants (Pss) responding at each of 9 CA doses during the NAC.To illustrate the variability of the outcome at each dose,the protocol specifies computation of 95% CIs for the proportion responding at each dose.A proportion is to record for each Ps a 0 for non-responder and 1 for responder &compute the mean of the 0 &1 values.Summary statistic for this method: a mean. After each dose,TNSS &TNSS Sneezing scores were recorded.TNSS (0-12) is a self-rated score computed as the sum of 4 subscale scores (0-3) measuring sneezing, runny nose, stuffy nose, & itchy nose symptoms (sxs).Pss provide a score on each subscale of 0, 1, 2, or 3(none, mild, moderate, or severe sxs, respectively).Pss cont'd receiving doses until either a TNSS (≥8 in adults,≥6 in children) or sneezing score threshold [TLV] of 3 was met.Assumption: Pss met TLV criteria for doses not recv'd beyond dose at which TLV criteria were initially met. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Sneezes at Each of Nine Doses of German Cockroach Allergen | Nine increasing doses of German cockroach allergen (0, 0.00381, 0.01204, 0.0380, 0.120, 0.379, 1.20, 3.78, and 11.9 mcg/mL) were administered during the Nasal Allergen Challenge (NAC). After administration of each dose, the number of times the participant sneezed was recorded. Participants continued receiving doses of German cockroach allergen until threshold criteria described in the primary endpoint were met. Number of sneezes was carried forward for doses not received beyond the dose at which the threshold criteria were initially met. Number of sneezes is summarized at each dose. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Highest Total Nasal Symptom Score (TNSS) | TNSS (0-12) is a participant rated score computed as the sum of four subscale scores (0-3) measuring sneezing, runny nose, stuffy nose, and itchy nose symptoms. Participants provide a score on each subscale of 0, 1, 2, or 3, indicating none, mild, moderate, or severe symptoms, respectively. The highest TNSS observed after administration of any of the German cockroach allergen doses received during the Nasal Allergen Challenge (NAC) is summarized. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Total Nasal Symptom Score (TNSS) | TNSS (0-12) is a participant rated score computed as the sum of four subscale scores (0-3) measuring sneezing, runny nose, stuffy nose, and itchy nose symptoms. Participants indicate a score on each subscale of 0, 1, 2, or 3, indicating none, mild, moderate, or severe symptoms, respectively. Change is computed by subtracting the TNSS score obtained after the nasal rinse administered prior to the Nasal Allergen Challenge from the TNSS score obtained at the last tolerated dose of German cockroach allergen received during the Nasal Allergen Challenge (NAC). A positive change score indicates that nasal symptoms increased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Peak Nasal Inspiratory Flow (PNIF) L/Min | PNIF is defined as the speed of inspiration of air in Liters per minute when breathing into the lungs. Change is computed by subtracting the PNIF score obtained after the nasal rinse administered prior to the Nasal Allergen Challenge (NAC) from the PNIF score obtained at the last tolerated dose of German cockroach allergen received during the NAC. A negative change score indicates that speed of inspiration decreased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Peak Expiratory Flow (PEF) L/Min | PEF is defined as the speed of expiration of air in Liters per minute when breathing out of the lungs. Change is computed by subtracting the PEF score obtained after the nasal rinse administered prior to the Nasal Allergen Challenge (NAC) from the PEF score obtained at the last tolerated dose of German cockroach allergen received during the NAC. A positive change score indicates that speed of expiration increased over the course of the Challenge, while a negative change score indicates speed of expiration decreased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Visual Analogue Score | Participants self-reported their score, reflecting the severity of their nasal symptoms-sneezing, runny nose, stuffy nose, itchy nose- on a Visual Analogue Scale (0 to 10 centimeters). The left-hand side of the scale (0) represents No Symptoms, and the right hand side of the scale (10) represents As Bad as I Can Imagine. Change is computed by subtracting the VAS score obtained after the nasal rinse administered prior to the Nasal Allergen Challenge (NAC) from the VAS score obtained at the last tolerated dose of German cockroach allergen received during the NAC. A positive change score indicates that nasal symptoms increased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Log Base 10 Tryptase in Nasal Secretions | Tryptase is a protein in the human body. Levels are hypothesized to be related to the extent of allergic response. Change is computed by subtracting the tryptase level prior to the Nasal Allergen Challenge (NAC) from the tryptase level after the last dose received during the NAC. A log base 10 transformation is applied to both baseline and post-baseline measures. A positive change score indicates that tryptase levels increased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 
| Change in Log Base 10 Albumin in Nasal Secretions | Albumin is a protein in the human body. Levels are hypothesized to be related to the extent of allergic response. Change is computed by subtracting the albumin level prior to the Nasal Allergen Challenge (NAC) from the albumin level after the last dose received during the NAC. A log base 10 transformation is applied to both baseline and post-baseline measures. A positive change score indicates that albumin levels increased over the course of the NAC. | NAC Baseline through last dose of German cockroach allergen administered during the NAC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Glycerinated German cockroach allergenic extract, Cockroach Nasal Allergen Challenge