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

NCT04129931 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-16815U24HL138998-03
• Study Type: interventional
• Target: 950
• Locations: 1 country
• Sites: 29

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• 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.

  Measured at 16 weeks after the start of treatment.

• 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.

  Measured at 16 weeks after the start of treatment.

Secondary Outcomes (7)

• CompEx Events Per Year

  Assessed over 16 weeks of treatment

• Forced Vital Capacity (FVC) Pre-bronchodilation

  Measured at 16 weeks after the start of treatment.

• FEV1 % Predicted Post-bronchodilation

  Measured at 16 weeks after the start of treatment.

• Exacerbations

  Assessed over 16 weeks of treatment

• Number of Participants With At Least One Asthma-Free Day

  Assessed over 16 weeks of treatment

Study Arms (5)

Medium Chain Triglycerides (MCT)

EXPERIMENTAL

Participants in this arm will receive Medium Chain Triglycerides (MCT) powder packets (12.5 g each) daily for the 16 week treatment period. Participants are assigned one packet per 500 kilocalories required to maintain bodyweight; the target dose for each participant is between 2 and 5 packets daily. Participants will mix the packets of MCT supplement powder into liquids or semi-solid food. Participants will be randomized to the treatment sequence and will receive either the active MCT or the matching placebo first or vice versa.

Drug: MCT; Other: Placebo

Clazakizumab

EXPERIMENTAL

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.

Drug: Clazakizumab; Other: Placebo

Broncho-Vaxom

EXPERIMENTAL

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.

Drug: Broncho-Vaxom; Other: Placebo

Imatinib

EXPERIMENTAL

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.

Drug: Imatinib Mesylate; Other: Placebo

Cavosonstat

EXPERIMENTAL

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.

Drug: Cavosonstat; Other: Placebo

Interventions

Cavosonstat DRUG

50 mg capsule orally twice a day for 16 weeks.

Also known as: N91115

Cavosonstat

Placebo OTHER

MCT Matching Placebo: MCT matching placebo packets. Mix 2-5 packets daily into liquid or food for 16 weeks. 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.

Broncho-Vaxom; Cavosonstat; Clazakizumab; Imatinib; Medium Chain Triglycerides (MCT)

MCT DRUG

Mix 2-5 packets daily into liquid or food for 16 weeks.

Also known as: Breathe Better Diet (BBD)

Medium Chain Triglycerides (MCT)

Clazakizumab DRUG

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.

Also known as: Anti-interleukin 6 monoclonal antibody (Anti-IL-6 mAb), BMS-945429, ALD518

Clazakizumab

Broncho-Vaxom DRUG

7 mg taken orally once a day, on an empty stomach, for 16 weeks

Also known as: OM-85 BV VEGETAL

Broncho-Vaxom

Imatinib Mesylate DRUG

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.

Also known as: Gleevec, Zoleta, Glivec, Ziatir

Imatinib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Forced Expiratory Volume in one second (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 oral corticosteriod (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 provocative concentration causing a 20% decrease in FEV1 (PC20) ≤16 mg/ml, or provocative dose causing a 20% decline in FEV1 (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+

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (29)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of Arizona Tucson

Tucson, Arizona, 85724, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

University of California San Diego: Airway Research & Clinical Trials Center

San Diego, California, 92103, United States

Location

University of California San Diego: La Jolla Altman Clinical Translation Research Institute

San Diego, California, 92121, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 802006, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Northwestern Universtiy

Chicago, Illinois, 60611, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10031, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27104, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

University Hospitals Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (18)

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• Woodcock J, LaVange LM. Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. N Engl J Med. 2017 Jul 6;377(1):62-70. doi: 10.1056/NEJMra1510062. No abstract available.

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• Fuhlbrigge AL, Bengtsson T, Peterson S, Jauhiainen A, Eriksson G, Da Silva CA, Johnson A, Sethi T, Locantore N, Tal-Singer R, Fageras M. A novel endpoint for exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised controlled trials. Lancet Respir Med. 2017 Jul;5(7):577-590. doi: 10.1016/S2213-2600(17)30218-7. Epub 2017 Jun 2.

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• Phipatanakul W, Mauger DT, Sorkness RL, Gaffin JM, Holguin F, Woodruff PG, Ly NP, Bacharier LB, Bhakta NR, Moore WC, Bleecker ER, Hastie AT, Meyers DA, Castro M, Fahy JV, Fitzpatrick AM, Gaston BM, Jarjour NN, Levy BD, Peters SP, Teague WG, Fajt M, Wenzel SE, Erzurum SC, Israel E; Severe Asthma Research Program. Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma. Am J Respir Crit Care Med. 2017 Jun 1;195(11):1439-1448. doi: 10.1164/rccm.201607-1453OC.

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• Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, Ayanian JZ, Nallamothu BK. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017 Apr 12;357:j1415. doi: 10.1136/bmj.j1415.

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• Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, Gaston B, Jarjour NN, Sorkness R, Calhoun WJ, Chung KF, Comhair SA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010 Feb 15;181(4):315-23. doi: 10.1164/rccm.200906-0896OC. Epub 2009 Nov 5.

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• Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger L, Engle LL, DiMango EA, Fahy JV, Israel E, Jarjour N, Kazani SD, Kraft M, Lazarus SC, Lemanske RF Jr, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Bleecker ER; National Heart, Lung, and Blood Institute Asthma Clinical Research Network. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010 Oct 28;363(18):1715-26. doi: 10.1056/NEJMoa1008770. Epub 2010 Sep 19.

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• Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Covar RA, Guilbert TW, Larsen G, Morgan WJ, Moss MH, Spahn JD, Taussig LM; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.

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• Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Bloomberg GR, Covar RA, Guilbert TW, Heldt G, Larsen G, Mellon MH, Morgan WJ, Moss MH, Spahn JD, Taussig LM; Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007 Jan;119(1):64-72. doi: 10.1016/j.jaci.2006.09.042. Epub 2006 Nov 30.

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  BACKGROUND

Related Links

• US Food and Drug Administration. Draft Guidance for Industry: Adaptive Designs for Clinical Trials of Drugs and Biologics.
• US Food and Drug Administration. Guidance for Clinical Trial Sponsors on Establishment and Operation of Clinical Trial Data Monitoring Committees
• International Conference on Harmonization (ICH) Harmonized Guideline E9 Statistical Principles for Clinical Trials

MeSH Terms

Conditions

Asthma

Interventions

clazakizumab; Broncho-Vaxom; Imatinib Mesylate; cavosonstat

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Anastasia Ivanova, PhD
• Organization: University of North Carolina at Chapel Hill

aivanova@bios.unc.edu

919-843-8086

Study Officials

• Anastasia Ivanova, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment sequence will be randomly assigned as either test treatment followed by matching placebo or vice-versa.

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 17, 2019
• Study Start: December 19, 2019
• Primary Completion: February 19, 2025
• Study Completion: March 19, 2025
• Last Updated: April 1, 2026
• Results First Posted: April 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)