PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study
Overview
- Phase
- Phase 2
- Intervention
- MCT
- Conditions
- Asthma
- Sponsor
- University of North Carolina, Chapel Hill
- Enrollment
- 395
- Locations
- 29
- Primary Endpoint
- The Juniper Asthma Control Questionnaire (ACQ-6)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
The primary objective of this study is to evaluate several interventions given to participants with severe asthma. Interventions are administered in a crossover manner with 16-week treatment periods followed by 8 to 16 week washout.
Detailed Description
PrecISE is a clinical study sponsored by the U.S. National Heart, Lung, and Blood Institute (NHLBI) to investigate several treatments for severe asthma. PrecISE will enroll 600 adults and teenagers (ages 12 years and older) with severe asthma who have symptoms that are not well-controlled on high dose of inhaled corticosteroids including those who have frequent asthma attacks. Each person who agrees to enroll in the PrecISE study will receive several treatments for research purposes based on their type of severe asthma. The goal of PrecISE is to understand how to treat different types of severe asthma, by using precision medicine. Precision medicine is an approach that targets treatments to defined subgroups of patients who share similar characteristics, for example, patients with a certain genetic variation or patients with high number of blood eosinophils. Researchers from over 30 locations across the US are involved in PrecISE.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated informed consent form
- •Started willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, age ≥ 12 years
- •No change in asthma medications for the past 2 months and use of medium or high dose inhaled corticosteroids (ICS) (defined by Table 1A) + an additional asthma controller/biologic (defined in Tables 1B and 1C). Participants entered into the run-in on medium dose ICS will be switched to high dose ICS. They must meet all entry criteria at the time of randomization including the criteria for uncontrolled asthma as assessed by symptoms during the two weeks prior to the randomization.
- •Baseline poor or uncontrolled asthma, defined as meeting at least one of the following:
- •FEV1 \<80% predicted (for adults ≥18) or FEV1\<90% (pediatric participants \<18) AND with 12% bronchodilator reversibility
- •Poor symptom control - Asthma Control Questionnaire ( ACQ-6) Score ≥1.5
- •≥1 exacerbation defined as a documented burst of systemic corticosteroids (\>3 days for adults and adolescents or \>1 day for adolescents treated with dexamethasone) in prior year for those not receiving chronic OCS or an increase in \>50% of baseline corticosteroid dose for ≥3 days in those receiving chronic OCS.
- •For patients on a biologic agent, at least one asthma exacerbation must have occurred at least 2 months after the initiation of the biologic agent. The definition of acceptable documentation for asthma exacerbations can be found in Section 6.5.
- •Evidence of asthma demonstrated by either bronchodilator reversibility or methacholine responsiveness either during the run-in or by historical evidence of either criterion if testing was performed under the same standards of the PrecISE Network at a PrecISE recruitment center. These criteria are defined as:
Exclusion Criteria
- •Current participation in an interventional trial (e.g. drugs, diets, etc.)
- •Enrollment in a clinical trial where the study medication was administered within the past 60 days or within 5 half-lives (whichever is greater)
- •Physician diagnosis of other chronic pulmonary disorders associated with asthma-like symptoms, including, but not limited to, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways
- •Receiving one or more immune-modulating therapies for diseases other than asthma
- •Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®)
- •Receiving aero allergen immunotherapy and not on at least 3 months of maintenance allergen immunotherapy
- •Underwent a bronchial thermoplasty within the last two years
- •Born before 35 weeks of gestation
- •Uncontrolled hypertension, defined as systolic blood pressure \>160 mm/Hg, or diastolic blood pressure \>100 mm/Hg
- •History of malignancy except non-melanoma skin cancer within the last five years
Arms & Interventions
Medium Chain Triglycerides (MCT)
Participants in this arm will receive Medium Chain Triglycerides (MCT) powder packets (10 g each) at each treatment visit at any point in the study. Participants will mix 1-2 packets of MCT supplement powder into liquids or semi-solid food and ingest 3 times a day during the 16-week treatment period. Participants will be randomized to the treatment sequence and will receive either the active MCT or the matching placebo first or vice versa.
Intervention: MCT
Medium Chain Triglycerides (MCT)
Participants in this arm will receive Medium Chain Triglycerides (MCT) powder packets (10 g each) at each treatment visit at any point in the study. Participants will mix 1-2 packets of MCT supplement powder into liquids or semi-solid food and ingest 3 times a day during the 16-week treatment period. Participants will be randomized to the treatment sequence and will receive either the active MCT or the matching placebo first or vice versa.
Intervention: Placebo
Clazakizumab
Participants randomized to this arm will receive a 12.5 mg dose of Clazakizumab via a subcutaneous injection at every study visit, every 4 weeks, during the 16-week treatment period at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Clazakizumab or the matching placebo first or vice versa.
Intervention: Clazakizumab
Clazakizumab
Participants randomized to this arm will receive a 12.5 mg dose of Clazakizumab via a subcutaneous injection at every study visit, every 4 weeks, during the 16-week treatment period at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Clazakizumab or the matching placebo first or vice versa.
Intervention: Placebo
Broncho-Vaxom
Participants randomized to this arm will receive 7 mg of Broncho-Vaxom once a day on an empty stomach for the 16-week treatment period duration at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Broncho-Vaxom or the matching placebo first or vice versa.
Intervention: Broncho-Vaxom
Broncho-Vaxom
Participants randomized to this arm will receive 7 mg of Broncho-Vaxom once a day on an empty stomach for the 16-week treatment period duration at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Broncho-Vaxom or the matching placebo first or vice versa.
Intervention: Placebo
Imatinib
At any point in the study, participants randomized to this arm will take two 100 mg Imatinib tablets orally once a day with a meal and an 8 oz glass of water for 2 weeks. Participants will then take four 100 mg tablets once a day with a meal and an 8 oz glass of water for 14 weeks. Participants will be randomized to the treatment sequence and will receive either the active Imatinib or the matching placebo first or vice versa.
Intervention: Imatinib Mesylate
Imatinib
At any point in the study, participants randomized to this arm will take two 100 mg Imatinib tablets orally once a day with a meal and an 8 oz glass of water for 2 weeks. Participants will then take four 100 mg tablets once a day with a meal and an 8 oz glass of water for 14 weeks. Participants will be randomized to the treatment sequence and will receive either the active Imatinib or the matching placebo first or vice versa.
Intervention: Placebo
Cavosonstat
Participants randomized to this arm will take one 50 mg Cavosonstat capsule orally twice a day for the 16-week treatment period duration at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Cavosonstat or the matching placebo first or vice versa.
Intervention: Cavosonstat
Cavosonstat
Participants randomized to this arm will take one 50 mg Cavosonstat capsule orally twice a day for the 16-week treatment period duration at any point in the study. Participants will be randomized to the treatment sequence and will receive either the active Cavosonstat or the matching placebo first or vice versa.
Intervention: Placebo
Outcomes
Primary Outcomes
The Juniper Asthma Control Questionnaire (ACQ-6)
Time Frame: Measured at 16 weeks after the start of treatment.
Asthma symptom control is assessed via ACQ-6, the average score of these six items (range 0-6). The seven-point response scale: 0 = 'totally controlled' and 6 = 'severely uncontrolled'. Negative change from baseline values indicate improved asthma control. Efficacy analyses will compare the end-of-period outcome values between test treatment and placebo.
CompEx events
Time Frame: Assessed over 16 weeks of treatment
CompEx is a composite outcome specific to asthma that combines clinically-relevant deteriorations captured by diary events with exacerbations. CompEx events include exacerbations and deterioration events defined based on daily recordings of peak expiratory flow (PEF) morning/evening (L/min), reliever use morning/evening (doses), symptoms morning/evening (score 0-3) from twice-daily recordings. Participants will be asked to describe their morning and symptoms using the following scale: 0-No symptoms to report, 3-I could not sleep because of my asthma/I could not perform my normal activities because of my asthma.
Forced Expiratory Volume in one second (FEV1) percent predicted
Time Frame: Measured at 16 weeks after the start of treatment.
Assessed prior to bronchodilator administration. Efficacy analyses will compare the end-of-period outcome values between test treatment and placebo.
Secondary Outcomes
- Symptom free days(Assessed over 16 weeks of treatment)
- Asthma free days(Assessed over 16 weeks of treatment)
- Forced Vital Capacity (FVC) pre-bronchodilation(Measured at 16 weeks after the start of treatment.)
- Time to first exacerbation(Assessed over 16 weeks of treatment)
- FEV1 post-bronchodilation(Measured at 16 weeks after the start of treatment.)
- Healthcare utilization(Assessed over 16 weeks of treatment)