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PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study

Primary Purpose

Asthma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MCT
Clazakizumab
Broncho-Vaxom
Imatinib Mesylate
Cavosonstat
Placebo
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Provision of signed and dated informed consent form
  2. Started willingness to comply with all study procedures and availability for the duration of the study
  3. Male or female, age ≥ 12 years
  4. 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.
  5. Baseline poor or uncontrolled asthma, defined as meeting at least one of the following:

    1. FEV1 <80% predicted (for adults ≥18) or FEV1<90% (pediatric participants <18) AND with 12% bronchodilator reversibility
    2. Poor symptom control - Asthma Control Questionnaire ( ACQ-6) Score ≥1.5
    3. ≥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 6.5.3.
  6. 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:

    1. An increase in FEV1 ≥12% (and 200 ml) after up to 8 puffs of albuterol OR
    2. Positive methacholine defined as PC20 ≤16 mg/ml, or PD20 ≤400 mcg/ml
  7. Agreement to adhere to Lifestyle Considerations (see Section 5.4) throughout study duration
  8. Owns a device compatible with the eDiary system used for CompEx, that is, an iOS 11+ device such as iPhone, iPad or iPod, or a smartphone or tablet running on Android 5.0+

Exclusion Criteria:

  1. Current participation in an interventional trial (e.g. drugs, diets, etc.)
  2. Enrollment in a clinical trial where the study medication was administered within the past 60 days or within 5 half-lives (whichever is greater)
  3. 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
  4. Receiving one or more immune-modulating therapies for diseases other than asthma
  5. Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®)
  6. Receiving aero allergen immunotherapy and not on at least 3 months of maintenance allergen immunotherapy
  7. Underwent a bronchial thermoplasty within the last two years
  8. Born before 35 weeks of gestation
  9. Uncontrolled hypertension, defined as systolic blood pressure >160 mm/Hg, or diastolic blood pressure >100 mm/Hg
  10. History of malignancy except non-melanoma skin cancer within the last five years
  11. History of smoking

    1. If <30 years old: Smoked for ≥5 pack-years*

      • Can still be enrolled if <30, smoked <5 5 pack years and none in past year, and normal (negative) urine cotinine
    2. If 30-39 years old: Smoked for ≥10 pack years

      • Can still be enrolled if ≥30, smoked <10 pack years and none in past year, provided participant demonstrates a normal (negative) urine cotinine
    3. If ≥40 years old: Smoked ≥15 pack years

      • Can still be enrolled if ≥40 years old, smoked <15 pack years and none in the last year, provided participant demonstrates normal (negative) urine cotinine. Patients with a smoking history of ≥10 to <15 pack years will also need to demonstrate a normal Diffusing Capacity for Carbon Monoxide (DLCO) (>70% predicted) * Smoking equivalent pack years. One pack of cigarettes a day for 1 year is equivalent to:
    1. 1 cigar or pipe per day for 1 year
    2. Smoked hookah or shisha =1 session per day for 1 year
    3. Vaped e-cigarettes =0.5 mLs e-liquid per day for 1 year, or =1 cartridge/tank/pod per day for 1 year
    4. 1 use of marijuana per day for 1 year
  12. Active use of any inhalant >1 time per month in the past year

    1. Active smoking of conventional tobacco, inhaling of marijuana or other drugs, or vaping of e-cigarettes or vape pods >1 time per month in the past year
    2. Any form of tobacco qualifies, such as: 1 cigarette, 1 hookah or shisha sessions, 1 cigar, 1 pipe, etc.
    3. Any electronic (e)-device included: e-cigarette e-cig, mod, vape pen, JUUL vaping device, e-cigar, e-hookah, e-pipe, vape pods, etc.
    4. Any form of inhaled marijuana, including smoking marijuana leaves or inhaling THC (tetrahydrocannabinol) via e-cigarette or device
  13. Substance abuse within the last year
  14. Unwillingness to practice medically acceptable birth control or complete abstinence during the study, current pregnancy, or lactation. Medically acceptable birth control/abstinence is defined as:

    1. Career, lifestyle, or sexual orientation precludes intercourse with a male partner
    2. For those in a monogamous relationship that precludes sexual activity with other partners, one of the sexual partners has been sterilized by vasectomy (in males) or hysterectomy and/or bilateral salpingo-oophorectomy (in females)
    3. Use of highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Contraception should be used for at least 1 month prior to screening, throughout study participation and for an additional 16 weeks after the end of the final test treatment.

      • Pregnancy tests will be given to each female participant prior to study enrollment and at each clinic visit
      • Each male participant will agree to inform his sexual partner(s) of the potential for harm to an unborn child. If a sexual partner becomes pregnant while he is participating in the study, he will notify study staff within 24 hours of receiving medical confirmation. His partner will be advised to promptly notify her doctor
      • Any pregnancy (of a participant or a partner) will be monitored for adverse events with respect to pregnancy outcome until one month after birth.
  15. Requirement for daily systemic corticosteroids above 10 mg of prednisone (or equivalent) per day for the past 2 months
  16. Respiratory infection within 1 month of screening
  17. Intubation for asthma in the last 12 months
  18. Use of warfarin, current or last 30 days
  19. Any clinically significant abnormal findings in the history, physical examination, vital signs, electrocardiogram, hematology or clinical chemistry during run-in period, which in the opinion of the site investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study
  20. Additional exclusions for specific interventions (and not for others) are listed in the Appendices I-VI, Section 5.2

Safety Exclusion Criteria:

Participants who meet the following criteria will be excluded from the study:

  1. Hemoglobin <10 g/dL
  2. Absolute Neutrophil Count (ANC) <1000/µl for black participants, <1500/µl for other participants
  3. Lymphocytes <500/µl
  4. Platelet count <100,000/µl
  5. Alanine Transaminase (ALT)/Aspartate Aminotransferase (AST) >2x upper limits of normal (ULN)
  6. Bilirubin ≥2x ULN
  7. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 sq m
  8. Positive Human Immunodeficiency Virus, Types 1 & 2 (HIV 1&2) Ab/Ag immunoassay followed by a confirmatory positive test (Geenius™ HIV-1/HIV-2 antibody differentiation immunoassay)
  9. Positive Hepatitis B surface Ag (active infection) or Hepatitis B core total antibody (marker of past infection that could reactivate)
  10. Positive Hepatitis C RNA test following positive Hepatitis C Antibody
  11. EKG with significant clinical findings

A positive QuantiFERON-TB (tuberculosis) Gold test requires further screening. A participant may be included in PrecISE if at least one of the following criteria are met:

  1. A chest radiograph (CXR) done within the last six months of the test that shows no evidence of active TB
  2. A chest CT scan done within the last six months of the test that shows no evidence of active TB
  3. Documentation of adequate treatment for latent TB In cases of an indeterminate QuantiFERON-TB test result, a second blood specimen must be drawn. A chest x-ray is not required if the participant has a negative QuantiFERON-TB Gold test.

Comorbid Conditions:

Comorbidities are commonly present in severe asthma. Specific questionnaires will be used to identify common comorbidities as follows:

  1. Sleep apnea: STOP-BANG
  2. GERD (GERD- Questionnaire)
  3. VCD (Pittsburgh vocal cord dysfunction index)
  4. Chronic Rhinitis Sinusitis (Sinonasal questionnaire-SNQ5)
  5. Depression-Anxiety (Hospital anxiety and depression Scale: HADS) These questionnaires are best used as screening tools. As such they typically have high sensitivity but relatively low specificity. Many of their symptoms overlap with the symptoms reported by participants with asthma who do not suffer from these conditions. Therefore, participants who meet the established cut offs for these questionnaires will need to be evaluated by the investigator to consider the clinical significance of the positive questionnaire based on history and physical and available testing. The investigator will need to judge the presence, severity and control of a specific condition and determine if it is sufficiently controlled to keep the participant in the PrecISE protocol. If the comorbid condition(s) is/are not adequately controlled, the investigator may refer the participant for further evaluation/treatment, prior to enrollment in PrecISE. Rescreening is permitted (after at least four weeks) to determine if the participant is able to move forward in PrecISE once the comorbid condition(s) is/are under adequate control. It is expected that some of the participants may also have other conditions such as cardiovascular disease, diabetes and obesity. These should be evaluated clinically as part of the complete history and physical done at initial evaluation. Their inclusions should be based on the investigator clinical judgement in line with good clinical practice principles.

Sites / Locations

  • Mayo Clinic ScottsdaleRecruiting
  • University of Arizona TucsonRecruiting
  • University of California DavisRecruiting
  • University of California San Diego: Airway Research & Clinical Trials CenterRecruiting
  • University of California San Diego: La Jolla Altman Clinical Translation Research InstituteRecruiting
  • University of California San FranciscoRecruiting
  • Children's Hospital ColoradoRecruiting
  • University of Colorado DenverRecruiting
  • National Jewish HealthRecruiting
  • Yale UniversityRecruiting
  • University of South FloridaRecruiting
  • University of Illinois at ChicagoRecruiting
  • Ann & Robert H. Lurie Children's HospitalRecruiting
  • Northwestern UniverstiyRecruiting
  • Rush UniversityRecruiting
  • University of ChicagoRecruiting
  • Riley Hospital for ChildrenRecruiting
  • University of KansasRecruiting
  • Boston Children's HospitalRecruiting
  • Brigham and Women's HospitalRecruiting
  • University of MichiganRecruiting
  • Washington UniversityRecruiting
  • Mount SinaiRecruiting
  • Columbia University Medical CenterRecruiting
  • Wake Forest UniversityRecruiting
  • Cleveland ClinicRecruiting
  • University Hospitals Rainbow Babies & Children's HospitalRecruiting
  • Vanderbilt UniversityRecruiting
  • University of Wisconsin-MadisonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Medium Chain Triglycerides (MCT)

Clazakizumab

Broncho-Vaxom

Imatinib

Cavosonstat

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Forced Expiratory Volume in one second (FEV1) percent predicted
Assessed prior to bronchodilator administration. Efficacy analyses will compare the end-of-period outcome values between test treatment and placebo.
The Juniper Asthma Control Questionnaire (ACQ-6)
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
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.

Secondary Outcome Measures

Forced Vital Capacity (FVC) pre-bronchodilation
Assessed prior to bronchodilator administration
FEV1 post-bronchodilation
Assessed after bronchodilator administration.
Time to first exacerbation
Symptom free days
Asthma free days
Healthcare utilization
Asthma-specific Emergency Department visits, asthma-specific hospital admissions, and asthma-specific ICU admissions.

Full Information

First Posted
October 15, 2019
Last Updated
May 16, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT04129931
Brief Title
PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study
Official Title
PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2019 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Treatment sequence will be randomly assigned as either test treatment followed by matching placebo or vice-versa.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Medium Chain Triglycerides (MCT)
Arm Type
Experimental
Arm Description
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.
Arm Title
Clazakizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Broncho-Vaxom
Arm Type
Experimental
Arm Description
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.
Arm Title
Imatinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Cavosonstat
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
MCT
Other Intervention Name(s)
Breathe Better Diet (BBD)
Intervention Description
Mix 1-2 packets, as instructed by a physician, into liquid or food three times daily
Intervention Type
Drug
Intervention Name(s)
Clazakizumab
Other Intervention Name(s)
Anti-interleukin 6 monoclonal antibody, Anti-IL-6 mAb, BMS-945429, ALD518
Intervention Description
12.5 mg subcutaneous injection given once every 4 weeks for 16 weeks. Lab driven dose reductions will be made based on safety lab data. If criteria are met for dose reduction, the participant will be reduced to a 6.25 mg dose.
Intervention Type
Drug
Intervention Name(s)
Broncho-Vaxom
Other Intervention Name(s)
OM-85 BV VEGETAL
Intervention Description
7 mg taken orally once a day, on an empty stomach, for 16 weeks
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Other Intervention Name(s)
Gleevec, Zoleta, Glivec, Ziatir
Intervention Description
Two 100 mg tablets orally once a day with a meal and an 8 oz glass of water for 2 weeks. If the drug is well tolerated, participants will titrate up to four 100 mg tablets once a day with a meal and an 8 oz glass of water for 14 weeks. Safety labs will be collected at each study visit to monitor the tolerability of each participant.
Intervention Type
Drug
Intervention Name(s)
Cavosonstat
Other Intervention Name(s)
N91115
Intervention Description
50 mg capsule orally twice a day for 16 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
MCT Matching Placebo: MCT matching placebo packets. Mix 1-2 packets, as instructed by a physician, into liquid or food three times daily Clazakizumab Matching Placebo: 12.5 mg subcutaneous saline injection given once every 4 weeks for 16 weeks. Broncho-Vaxom Matching Placebo: 7 mg matching placebo taken orally once a day on an empty stomach for 16 weeks Imatinib Matching Placebo: Two 100 mg placebo tablets orally once a day with a meal and an 8 oz glass of water for 2 weeks. Then four 100 mg placebo tablets once a day with a meal and an 8 oz glass of water for 14 weeks. Cavosonstat Matching Placebo: 50 mg matching placebo capsule orally twice a day for 16 weeks.
Primary Outcome Measure Information:
Title
Forced Expiratory Volume in one second (FEV1) percent predicted
Description
Assessed prior to bronchodilator administration. Efficacy analyses will compare the end-of-period outcome values between test treatment and placebo.
Time Frame
Measured at 16 weeks after the start of treatment.
Title
The Juniper Asthma Control Questionnaire (ACQ-6)
Description
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.
Time Frame
Measured at 16 weeks after the start of treatment.
Title
CompEx events
Description
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.
Time Frame
Assessed over 16 weeks of treatment
Secondary Outcome Measure Information:
Title
Forced Vital Capacity (FVC) pre-bronchodilation
Description
Assessed prior to bronchodilator administration
Time Frame
Measured at 16 weeks after the start of treatment.
Title
FEV1 post-bronchodilation
Description
Assessed after bronchodilator administration.
Time Frame
Measured at 16 weeks after the start of treatment.
Title
Time to first exacerbation
Time Frame
Assessed over 16 weeks of treatment
Title
Symptom free days
Time Frame
Assessed over 16 weeks of treatment
Title
Asthma free days
Time Frame
Assessed over 16 weeks of treatment
Title
Healthcare utilization
Description
Asthma-specific Emergency Department visits, asthma-specific hospital admissions, and asthma-specific ICU admissions.
Time Frame
Assessed over 16 weeks of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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 6.5.3. 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: An increase in FEV1 ≥12% (and 200 ml) after up to 8 puffs of albuterol OR Positive methacholine defined as PC20 ≤16 mg/ml, or PD20 ≤400 mcg/ml Agreement to adhere to Lifestyle Considerations (see Section 5.4) throughout study duration Owns a device compatible with the eDiary system used for CompEx, that is, an iOS 11+ device such as iPhone, iPad or iPod, or a smartphone or tablet running on Android 5.0+ 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 History of smoking If <30 years old: Smoked for ≥5 pack-years* Can still be enrolled if <30, smoked <5 5 pack years and none in past year, and normal (negative) urine cotinine If 30-39 years old: Smoked for ≥10 pack years Can still be enrolled if ≥30, smoked <10 pack years and none in past year, provided participant demonstrates a normal (negative) urine cotinine If ≥40 years old: Smoked ≥15 pack years Can still be enrolled if ≥40 years old, smoked <15 pack years and none in the last year, provided participant demonstrates normal (negative) urine cotinine. Patients with a smoking history of ≥10 to <15 pack years will also need to demonstrate a normal Diffusing Capacity for Carbon Monoxide (DLCO) (>70% predicted) * Smoking equivalent pack years. One pack of cigarettes a day for 1 year is equivalent to: 1 cigar or pipe per day for 1 year Smoked hookah or shisha =1 session per day for 1 year Vaped e-cigarettes =0.5 mLs e-liquid per day for 1 year, or =1 cartridge/tank/pod per day for 1 year 1 use of marijuana per day for 1 year Active use of any inhalant >1 time per month in the past year Active smoking of conventional tobacco, inhaling of marijuana or other drugs, or vaping of e-cigarettes or vape pods >1 time per month in the past year Any form of tobacco qualifies, such as: 1 cigarette, 1 hookah or shisha sessions, 1 cigar, 1 pipe, etc. Any electronic (e)-device included: e-cigarette e-cig, mod, vape pen, JUUL vaping device, e-cigar, e-hookah, e-pipe, vape pods, etc. Any form of inhaled marijuana, including smoking marijuana leaves or inhaling THC (tetrahydrocannabinol) via e-cigarette or device Substance abuse within the last year Unwillingness to practice medically acceptable birth control or complete abstinence during the study, current pregnancy, or lactation. Medically acceptable birth control/abstinence is defined as: Career, lifestyle, or sexual orientation precludes intercourse with a male partner For those in a monogamous relationship that precludes sexual activity with other partners, one of the sexual partners has been sterilized by vasectomy (in males) or hysterectomy and/or bilateral salpingo-oophorectomy (in females) Use of highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Contraception should be used for at least 1 month prior to screening, throughout study participation and for an additional 16 weeks after the end of the final test treatment. Pregnancy tests will be given to each female participant prior to study enrollment and at each clinic visit Each male participant will agree to inform his sexual partner(s) of the potential for harm to an unborn child. If a sexual partner becomes pregnant while he is participating in the study, he will notify study staff within 24 hours of receiving medical confirmation. His partner will be advised to promptly notify her doctor Any pregnancy (of a participant or a partner) will be monitored for adverse events with respect to pregnancy outcome until one month after birth. Requirement for daily systemic corticosteroids above 10 mg of prednisone (or equivalent) per day for the past 2 months Respiratory infection within 1 month of screening Intubation for asthma in the last 12 months Use of warfarin, current or last 30 days Any clinically significant abnormal findings in the history, physical examination, vital signs, electrocardiogram, hematology or clinical chemistry during run-in period, which in the opinion of the site investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study Additional exclusions for specific interventions (and not for others) are listed in the Appendices I-VI, Section 5.2 Safety Exclusion Criteria: Participants who meet the following criteria will be excluded from the study: Hemoglobin <10 g/dL Absolute Neutrophil Count (ANC) <1000/µl for black participants, <1500/µl for other participants Lymphocytes <500/µl Platelet count <100,000/µl Alanine Transaminase (ALT)/Aspartate Aminotransferase (AST) >2x upper limits of normal (ULN) Bilirubin ≥2x ULN Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 sq m Positive Human Immunodeficiency Virus, Types 1 & 2 (HIV 1&2) Ab/Ag immunoassay followed by a confirmatory positive test (Geenius™ HIV-1/HIV-2 antibody differentiation immunoassay) Positive Hepatitis B surface Ag (active infection) or Hepatitis B core total antibody (marker of past infection that could reactivate) Positive Hepatitis C RNA test following positive Hepatitis C Antibody EKG with significant clinical findings A positive QuantiFERON-TB (tuberculosis) Gold test requires further screening. A participant may be included in PrecISE if at least one of the following criteria are met: A chest radiograph (CXR) done within the last six months of the test that shows no evidence of active TB A chest CT scan done within the last six months of the test that shows no evidence of active TB Documentation of adequate treatment for latent TB In cases of an indeterminate QuantiFERON-TB test result, a second blood specimen must be drawn. A chest x-ray is not required if the participant has a negative QuantiFERON-TB Gold test. Comorbid Conditions: Comorbidities are commonly present in severe asthma. Specific questionnaires will be used to identify common comorbidities as follows: Sleep apnea: STOP-BANG GERD (GERD- Questionnaire) VCD (Pittsburgh vocal cord dysfunction index) Chronic Rhinitis Sinusitis (Sinonasal questionnaire-SNQ5) Depression-Anxiety (Hospital anxiety and depression Scale: HADS) These questionnaires are best used as screening tools. As such they typically have high sensitivity but relatively low specificity. Many of their symptoms overlap with the symptoms reported by participants with asthma who do not suffer from these conditions. Therefore, participants who meet the established cut offs for these questionnaires will need to be evaluated by the investigator to consider the clinical significance of the positive questionnaire based on history and physical and available testing. The investigator will need to judge the presence, severity and control of a specific condition and determine if it is sufficiently controlled to keep the participant in the PrecISE protocol. If the comorbid condition(s) is/are not adequately controlled, the investigator may refer the participant for further evaluation/treatment, prior to enrollment in PrecISE. Rescreening is permitted (after at least four weeks) to determine if the participant is able to move forward in PrecISE once the comorbid condition(s) is/are under adequate control. It is expected that some of the participants may also have other conditions such as cardiovascular disease, diabetes and obesity. These should be evaluated clinically as part of the complete history and physical done at initial evaluation. Their inclusions should be based on the investigator clinical judgement in line with good clinical practice principles.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alison Marquis
Phone
919-962-3267
Email
precise@unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anastasia Ivanova
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Evans
Email
evans.alexandria@mayo.edu
First Name & Middle Initial & Last Name & Degree
Matthew Rank, MD
Facility Name
University of Arizona Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raymond Skeps
Email
rpskeps@arizona.edu
First Name & Middle Initial & Last Name & Degree
Eugene Bleecker, MD
First Name & Middle Initial & Last Name & Degree
Monica Kraft, MD
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tina Tham
Email
ttham@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Nicholas Kenyon, MD
Facility Name
University of California San Diego: Airway Research & Clinical Trials Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damaris Diaz
Email
dad003@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Praveen Akuthota
Facility Name
University of California San Diego: La Jolla Altman Clinical Translation Research Institute
City
San Diego
State/Province
California
ZIP/Postal Code
92121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damaris Diaz
Email
dad003@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Praveen Akuthota, MD
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jade Vi
Email
jade.vi@ucsf.edu
First Name & Middle Initial & Last Name & Degree
John Fahy, MD
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonya Belimezova
Email
sonya.belimezova@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Stanley Szefler
First Name & Middle Initial & Last Name & Degree
Andrew Liu
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abigail Hills
Email
abigail.hills@cuanschutz.edu
First Name & Middle Initial & Last Name & Degree
Fernando Holguin, MD
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
802006
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juno Pak
Email
PakJ@NJHealth.org
First Name & Middle Initial & Last Name & Degree
Michael Wechsler, MD
First Name & Middle Initial & Last Name & Degree
Ronina Covar, MD
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole Grant
Email
Nicole.Grant@yale.edu
First Name & Middle Initial & Last Name & Degree
Geoffrey Chupp, MD
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Renee Smith
Email
catherinesmith@health.usf.edu
First Name & Middle Initial & Last Name & Degree
Juan Carlos Cardet, MD
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60608
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy Hasse
Email
whasse2@UIC.EDU
First Name & Middle Initial & Last Name & Degree
Jerry Krishnan, MD
Facility Name
Ann & Robert H. Lurie Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Opinderjit Kaur
Email
okaur@luriechildrens.org
First Name & Middle Initial & Last Name & Degree
Rajesh Kumar, MD
Facility Name
Northwestern Universtiy
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jenny Hixon
Email
j-franzen@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Sharon Rosenberg
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grace Li
Email
jia_li@rush.edu
First Name & Middle Initial & Last Name & Degree
James Moy, MD
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carly Jackson
Email
carlyj@medicine.bsd.uchicago.edu
First Name & Middle Initial & Last Name & Degree
Steve White, MD
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa France
Email
lfrance@iu.edu
First Name & Middle Initial & Last Name & Degree
James Chmiel, MD
First Name & Middle Initial & Last Name & Degree
Benjamin Gaston, MD
Facility Name
University of Kansas
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanessa Curtis
Email
vcurtis@kumc.edu
First Name & Middle Initial & Last Name & Degree
Mario Castro, MD
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amparito Cunningham
Phone
857-218-5531
Email
amparito.cunningham@childrens.harvard.edu
First Name & Middle Initial & Last Name & Degree
Wanda Phipatannnnakul, MD
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Angeles Cinelli
Phone
617-732-8114
Email
mcinelli@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Elliot Israel, MD
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa McCloskey
Email
lmcclosk@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Njira Lugogo, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tammy Quinones
Email
tquinones@wustl.edu
First Name & Middle Initial & Last Name & Degree
Kaharu Sumino, MD
Facility Name
Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Kessler
Email
jonathan.kessler1@mssm.edu
First Name & Middle Initial & Last Name & Degree
Linda Rogers, MD
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jotti Saroya
Email
tks2127@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Emily DiMango, MD
Facility Name
Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Pippins
Email
apippins@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Wendy Moore, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Koo
Email
KOOM@ccf.org
First Name & Middle Initial & Last Name & Degree
Serpil Erzurum, MD
Facility Name
University Hospitals Rainbow Babies & Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Veri
Email
laura.veri@uhhospitals.org
First Name & Middle Initial & Last Name & Degree
Kristie Ross, MD
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Madison
Email
julie.l.madison@vumc.org
First Name & Middle Initial & Last Name & Degree
Leonard Bacharier, MD
Facility Name
University of Wisconsin-Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Bach
Email
jcbach@medicine.wisc.edu
First Name & Middle Initial & Last Name & Degree
Loren Denlinger, MD
First Name & Middle Initial & Last Name & Degree
Nizar Jarjour, MD

12. IPD Sharing Statement

Plan to Share IPD
No
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Learn more about this trial

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study

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