Summary

for people ages 12 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
John Fahy, MDNgoc Ly, MD

Description

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.

Details

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 800 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, as well as sites in Canada and the United Kingdom, are involved in PrecISE.

Keywords

Asthma Imatinib Mesylate Broncho-Vaxom MCT Clazakizumab Cavosonstat Itacitinib Medium Chain Triglycerides (MCT) Imatinib

Eligibility

You can join if…

Open to people ages 12 years and up

  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:
  6. FEV1 <80% predicted (for adults ≥18) or FEV1<90% (pediatric participants <18) AND with 12% bronchodilator reversibility
  7. Poor symptom control - Asthma Control Questionnaire ( ACQ-6) Score ≥1.5
  8. ≥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.
  9. 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.
  10. 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:
  11. An increase in FEV1 ≥12% (and 200 ml) after up to 8 puffs of albuterol OR
  12. Positive methacholine defined as PC20 ≤16 mg/ml, or PD20 ≤400 mcg/ml
  13. Agreement to adhere to Lifestyle Considerations (see Section 5.4) throughout study duration
  14. 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+

You CAN'T join if...

  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
  12. If <30 years old: Smoked for ≥5 pack-years*
  13. Can still be enrolled if <30, smoked <5 5 pack years and none in past year, and normal (negative) urine cotinine
  14. If 30-39 years old: Smoked for ≥10 pack years
  15. Can still be enrolled if ≥30, smoked <10 pack years and none in past year, provided participant demonstrates a normal (negative) urine cotinine
  16. If ≥40 years old: Smoked ≥15 pack years
  17. 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:
  18. 1 cigar or pipe per day for 1 year
  19. Smoked hookah or shisha =1 session per day for 1 year
  20. Vaped e-cigarettes =0.5 mLs e-liquid per day for 1 year, or =1 cartridge/tank/pod per day for 1 year
  21. 1 use of marijuana per day for 1 year
  22. . Active use of any inhalant >1 time per month in the past year
  23. 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
  24. Any form of tobacco qualifies, such as: 1 cigarette, 1 hookah or shisha sessions, 1 cigar, 1 pipe, etc.
  25. Any electronic (e)-device included: e-cigarette e-cig, mod, vape pen, JUUL vaping device, e-cigar, e-hookah, e-pipe, vape pods, etc.
  26. Any form of inhaled marijuana, including smoking marijuana leaves or inhaling THC (tetrahydrocannabinol) via e-cigarette or device
  27. . Substance abuse within the last year
  28. . 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:
  29. Career, lifestyle, or sexual orientation precludes intercourse with a male partner
  30. 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)
  31. 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.
  32. Pregnancy tests will be given to each female participant prior to study enrollment and at each clinic visit
  33. 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
  34. Any pregnancy (of a participant or a partner) will be monitored for adverse events with respect to pregnancy outcome until one month after birth.
  35. . Requirement for daily systemic corticosteroids above 10 mg of prednisone (or equivalent) per day for the past 2 months
  36. . Respiratory infection within 1 month of screening
  37. . Intubation for asthma in the last 12 months
  38. . Use of warfarin, current or last 30 days
  39. . 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
  40. . 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.

Locations

  • University of California San Francisco not yet accepting patients
    San Francisco California 94143 United States
  • University of California San Francisco Benioff Children's Hospital not yet accepting patients
    San Francisco California 94158 United States

Lead Scientists

  • John Fahy, MD
    I am a Professor of Medicine in the Division of Pulmonary and Critical Care Medicine and the Department of Medicine at UCSF. I direct a research program in asthma and other airway diseases that is human centered and focused on uncovering disease mechanisms and improving treatment.
  • Ngoc Ly, MD
    My research has focused on the influences of heredity, as well as prenatal and infant environmental exposures ( including environmental, microbial, and nutritional influences) on immune responses and clinical symptoms of allergy and asthma.