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Moderate to Severe AsthmaPhase 4EPIPHANYNCT06385236

Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping

A Phase 4 study testing Dupilumab and Benralizumab in people with Moderate to Severe Asthma, run by University of California, San Diego at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

In this study, a new method will be used to evaluate response to 2 approved biologic therapies, and assess how well each patient responds to each asthma treatment. This study will measure the response to these treatments using genomic and biologic measurements obtained from participants biosamples. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Moderate to Severe Asthma
What is being tested?
Dupilumab and Benralizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
3 sitesUnited States
Study dates
19 Feb 2024to 31 Jan 2028
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Stable asthma medications: No change in asthma medications for the past 2 months:
  • Use of medium or high dose inhaled corticosteroids (ICS) AND
  • Use of an additional asthma controller medication.
  • Baseline poor or uncontrolled asthma.
  • Evidence of asthma demonstrated by either bronchodilator reversibility (either at screening or by historical evidence) or methacholine responsiveness (by historical evidence).
  • Agreement to adhere to Lifestyle Considerations throughout study duration.

Who cannot join

  • Current participation in an interventional trial (e.g. drugs, diets, etc.).
  • Currently on an asthma biologic or having been on biologic within 3 months of screening.
  • 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. This includes biologics that are also approved for asthma.
  • Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®).
Show all 23Show fewer
  • 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 30 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 <45 years old: Smoked for ≥5 pack-years*
  • If ≥45 years old: Smoked ≥ 10 pack years.
  • Active use of any inhalant >1 time per month in the past year.
  • Substance abuse within the last year.
  • Unwillingness to practice medically acceptable birth control or complete abstinence during the study, current pregnancy, or lactation.
  • Requirement for daily systemic corticosteroids at the time of screening.
  • Respiratory infection within 1 month of screening.
  • Intubation for asthma in the last 12 months.
  • 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.
  • BMI > 38.
  • Allergic to any of the drugs, biologics or chemicals used in this study.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Trial Operations and Data Management Specialist UA-DCC contact

520-626-9552

bio5-epiphanydcc@arizona.edu

United States3 sites, 3 recruiting

  • University of California, San Diego

    La Jolla, California, 92093

    Asthma Research Team, 619-431-0995, asthma@health.ucsd.edu

    Kelan Tantisira, MD

    Recruiting

  • Yale University

    New Haven, Connecticut, 06520

    Katherine Spaulding, 203-737-5572, katherine.spaulding@yale.edu

    Geoffrey L Chupp, MD

    Recruiting

  • Mayo Clinic

    Scottsdale, Arizona, 85259

    Karalyn Folmes, Ph.D., 480-301-4298, folmes.karalyn@mayo.edu

    Gene R Bleecker, MD

    Recruiting

Other trials in United States

About this study

In this study, a new method will be used to evaluate response to 2 approved biologic therapies, and assess how well each patient responds to each asthma treatment. This study will measure the response to these treatments using genomic and biologic measurements obtained from participants biosamples.

By evaluating response to 2 different biologic therapies, this study has the potential to provide an in-depth understanding of the mechanisms underlying severe asthma that will inform and change treatment decisions, and may ultimately lead to a change in the way that asthma patients are evaluated for potential personalized therapies and maximize the probability that the subject will respond to treatment.

Read the detailed description

The study design mirrors standard of care for this study population (moderate to severe asthmatics) in that the procedures are drugs and not outside of standard of care and not experimental. The drugs were chosen based on safety, availability, and their use in patient care. The use of the drugs/biologics and other asthma related processes and procedures are not experimental. Eligible participants will have the option of receiving Symbicort as their controller medication, during their involvement in the study.

The study focuses on a series of pre- and post-therapy characterizations or 'evoked phenotypes' that are not studied in traditional randomized clinical trials. Specifically, in a broad spectrum of 120 moderate-severe nonsmoking asthmatics, after evaluating pharmacologic response to systemic corticosteroids, each subject will undergo 'evoked phenotypes' with anti-IL-5R (benralizumab) and anti-IL-4Rα (dupilumab) in a random order along with comprehensive transcriptomic data interrogation prior to and during each therapeutic intervention.

A specific strength of our approach is the longitudinal assessment of within individual response related to therapeutic immunomodulation combined with state-of-the-art computational methods that will further define disease biology.

Current biomarkers are inadequate to distinguish responders and non-responders because they are not sensitive or specific enough for true predictive precision medicine. This study will use novel genomics approaches to assess and predict responses using therapy-induced phenotypes across a spectrum of asthma severity and endotypes.

Being tested
Dupilumab, Benralizumab
Keywords
Asthma
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DupilumabBiological

    Also called Dupixent

    Dupilumab, an interleukin-4 receptor treatment, will be administered through a subcutaneous injection, the initial dose of 600 mg will be administered at two different injection sites (300 mg per injection), followed by a single dose of 300 mg administered every other week (Q2W).

    Participants may self-administer injection after proper training.

  • BenralizumabBiological

    Also called Fasenra

    Benralizumab, an interleukin-5 receptor treatment, will be administered through a subcutaneous injection every 4 weeks (Q4W).

    Participants may self-administer injection after proper training.

Study groups in NCT06385236
Study groupRoleWhat they receive
DupilumabActive comparator600 mg once subcutaneously (given as two 300 mg injections), followed by 300 mg subcutaneously every other week.
Receives: Biological: Dupilumab
BenralizumabActive comparator30 mg subcutaneously every 4 weeks.
Receives: Biological: Benralizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Predicting asthma outcomes and therapeutic responses

    The primary outcomes of our therapeutic assessments are the genomic signatures that will identify novel predictive biomarkers and provide mechanistic insights to the heterogeneous response to a specific therapy. Our genomic signatures will focus on global gene expression using RNA sequencing (RNA-Seq).

    Measured: After 16 weeks (for each biologic)

  2. Responses to the biologic therapies at the single cell level

    Single cell (sc) RNA-Seq on sputum and blood samples will be assayed at baseline and after each evoked (drug) phenotype.

    Measured: After 16 weeks (for each biologic)

  3. Unique asthma subgroups clinical and molecular endotype approaches

    Clinical and molecular endotype will be independently assessed for their prognostic association with treatment response through scRNA-seq and RNA-sequencing data at baseline and following therapy.

    Measured: After 16 weeks (for each biologic)

Secondary outcomes (4)

  1. Asthma Control Questionnaire (ACQ)

    A simple questionnaire (6-item questionnaire) to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment

    Measured: Assessed through study completion, an average of 60 weeks

  2. CompEx events

    CompEx is a composite outcome specific to asthma that combines clinically relevant deteriorations captured by diary events with exacerbations, thereby providing an increase in power compared to using exacerbations alone. CompEx events include exacerbations and deterioration events.

    Measured: Assessed through study completion, an average of 60 weeks

  3. Asthma Quality of Life Questionnaire (AQLQ)

    A disease-specific health-related quality of life instrument that taps both physical and emotional impact of disease. (32 items with 2-week recall)

    Measured: Assessed through study completion, an average of 60 weeks

  4. Forced expiratory volume in 1 second (FEV1)

    Lung function (FEV1) will be measured prior to bronchodilator administration by spirometry test.

    Measured: Assessed through study completion, an average of 60 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2024
  2. Study start19 Feb 2024
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion31 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
The study is significant in determining molecular disease endotypes in a large group of moderate to severe asthmatics. By evaluating within-person genomic level changes and response to 2 different biologic therapies, this study has the potential to provide an in-depth understanding of the mechanisms underlying severe asthma that will inform and change treatment decisions.
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06385236
Sponsor's protocol ID
804913
Other IDs
R01HL161362
Acronym
EPIPHANY
Status last verified
Aug 2024
First submitted
2 Apr 2024
Last updated
19 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: This study will be conducted in accordance with the following publication and data sharing policies and regulations: National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this study will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.

Publications

  • Bleecker ER, Menzies-Gow AN, Price DB, Bourdin A, Sweet S, Martin AL, Alacqua M, Tran TN. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management. Am J Respir Crit Care Med. 2020 Feb 1;201(3):276-293. doi: 10.1164/rccm.201904-0903SO.

    PubMed 31525297

  • Nelson RK, Bush A, Stokes J, Nair P, Akuthota P. Eosinophilic Asthma. J Allergy Clin Immunol Pract. 2020 Feb;8(2):465-473. doi: 10.1016/j.jaip.2019.11.024. Epub 2019 Nov 28.

    PubMed 31786254

  • Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018 Feb 24;391(10122):783-800. doi: 10.1016/S0140-6736(17)33311-1. Epub 2017 Dec 19.

    PubMed 29273246

  • Drazen JM, Harrington D. New Biologics for Asthma. N Engl J Med. 2018 Jun 28;378(26):2533-2534. doi: 10.1056/NEJMe1806037. Epub 2018 May 21. No abstract available.

    PubMed 29782236

  • 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.

    PubMed 28583396

  • 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.

    PubMed 19892860

  • 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.

    PubMed 27967215

  • Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, Gaga M, Kellermeyer L, Khurana S, Knight S, McDonald VM, Morgan RL, Ortega VE, Rigau D, Subbarao P, Tonia T, Adcock IM, Bleecker ER, Brightling C, Boulet LP, Cabana M, Castro M, Chanez P, Custovic A, Djukanovic R, Frey U, Frankemolle B, Gibson P, Hamerlijnck D, Jarjour N, Konno S, Shen H, Vitary C, Bush A. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020 Jan 2;55(1):1900588. doi: 10.1183/13993003.00588-2019. Print 2020 Jan.

    PubMed 31558662

  • Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. doi: 10.1183/09031936.00202013. Epub 2013 Dec 12.

    PubMed 24337046

  • Fuhlbrigge A, Peden D, Apter AJ, Boushey HA, Camargo CA Jr, Gern J, Heymann PW, Martinez FD, Mauger D, Teague WG, Blaisdell C. Asthma outcomes: exacerbations. J Allergy Clin Immunol. 2012 Mar;129(3 Suppl):S34-48. doi: 10.1016/j.jaci.2011.12.983.

    PubMed 22386508

  • Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available.

    PubMed 10619836

  • Coates AL, Wanger J, Cockcroft DW, Culver BH; Bronchoprovocation Testing Task Force: Kai-Hakon Carlsen; Diamant Z, Gauvreau G, Hall GL, Hallstrand TS, Horvath I, de Jongh FHC, Joos G, Kaminsky DA, Laube BL, Leuppi JD, Sterk PJ. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017 May 1;49(5):1601526. doi: 10.1183/13993003.01526-2016. Print 2017 May.

    PubMed 28461290

  • Tiwari A, Li J, Kho AT, Sun M, Lu Q, Weiss ST, Tantisira KG, McGeachie MJ. COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma. J Allergy Clin Immunol. 2021 Jun;147(6):2181-2190. doi: 10.1016/j.jaci.2020.11.048. Epub 2020 Dec 29.

    PubMed 33385444

  • Sharma S, Kho AT, Chhabra D, Qiu W, Gaedigk R, Vyhlidal CA, Leeder JS, Barraza-Villarreal A, London SJ, Gilliland F, Raby BA, Weiss ST, Tantisira KG. Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response. Am J Respir Cell Mol Biol. 2015 May;52(5):543-53. doi: 10.1165/rcmb.2014-0109OC.

    PubMed 25192440

  • Howrylak JA, Moll M, Weiss ST, Raby BA, Wu W, Xing EP. Gene expression profiling of asthma phenotypes demonstrates molecular signatures of atopy and asthma control. J Allergy Clin Immunol. 2016 May;137(5):1390-1397.e6. doi: 10.1016/j.jaci.2015.09.058. Epub 2016 Jan 12.

    PubMed 26792209

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dupilumab and Benralizumab in people with Moderate to Severe Asthma, run by University of California, San Diego at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trial Operations and Data Management Specialist UA-DCC (520-626-9552, bio5-epiphanydcc@arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Predicting asthma outcomes and therapeutic responses (time frame: After 16 weeks (for each biologic)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06385236, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.

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