Sustained Asthma Remission and Reduced RElapse Using a COmprehensive Management Strategy Randomized Control Trial

Current clinical assessments and conventional biomarkers have limited ability to predict which patients will respond most favorably to treatment.

This pilot randomized controlled trial will evaluate whether specialized biomarkers of airway inflammation and lung abnormalities can better predict important asthma outcomes, including remission and relapse, than conventionally available biomarkers. The study will also assess whether a comprehensive management strategy guided by specialized biomarker assessments improves asthma outcomes compared with standard care.

Fifty adults with severe asthma who are initiating biologic therapy will be enrolled and randomized in a 1:1 ratio to either a standard of care group or a comprehensive management group. Participants assigned to the comprehensive management group will have treatment decisions informed by specialized biomarker results, while clinicians caring for participants in the standard of care group will remain blinded to these results.

Participants will be followed for 12 months and will undergo study assessments that include asthma questionnaires, pulmonary function testing, fractional exhaled nitric oxide (FeNO) testing, blood biomarker assessments, sputum cell analysis, computed tomography (CT) imaging, and magnetic resonance imaging (MRI). The study will compare asthma remission, relapse, airway inflammation, and structural airway abnormalities between groups.

The findings from this study will provide preliminary evidence regarding the utility of specialized biomarkers and biomarker-guided management strategies in severe asthma and may inform future larger clinical trials and personalized treatment approaches.

Inclusion criteria

• • Patient understands study procedures and is will to participate in the study as indicated by the patient's signature.

• Provision of written, informed consent prior to any study specific procedures.
• Males and females ≥ 18 years of age.
• Diagnosis of severe asthma, as defined by ATS/ERS guidelines (requiring high-dose ICS plus second controller and/or OCS, or uncontrolled despite this therapy).
• Eligible for initiation of biologic therapy for treatment of asthma.
• Women of childbearing potential (after menarche) must ensure that they are using an effective form of birth control for at least 2 months prior to each imaging visit. Examples of effective birth control include:
• True sexual abstinence
• A vasectomized sexual partner
• Implanon®
• Female sterilization by tubal occlusion
• Effective intrauterine device (IUD)/levonogestrel intrauterine system (IUS)
• Depo-Provera™ injections
• Oral contraceptive
• Evra Patch™
• Nuvaring™
• Women of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrollment, throughout the study duration, and X weeks after last dose of study drug, with negative urine pregnancy test result at Visit 1 and Visit 5.
• Male participants who are sexually active must agree to use a double barrier method of contraception (male condom with diaphragm or male condom with cervical cap) from the first dose of the study drug until X weeks after last dose.

Exclusion criteria

• • Primary respiratory diagnoses other than asthma (e.g., COPD, bronchiectasis).

• Patients with incomplete medical records.
• Patients who have received biologic treatment for asthma within the last 6 months.
• Patient has an implanted mechanically, electrically, or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist).
• In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI or CT, such as severe claustrophobia.
• Patients with contraindications to PFT, sputum induction, CT or MRI imaging.
• Patients who are pregnant or breastfeeding.
• Patients who are unable or unwilling to comply with study procedures.