Anakinra Rescue Treatment for Moderate Asthma Attacks (ARTMA)

Официальное название

Anakinra Rescue Treatment for Moderate Asthma Attacks (ARTMA) Pilot Study

Обзор

In this single center, interventional pilot study, 40 participants at high risk for future exacerbation will be randomized to anakinra (v. placebo control) treatment for home administration as part of an asthma action plan (AAP) and monitored through their first moderate asthma exacerbation, triggering treatment dosing over a 26 week period. Key feasibility questions will be assessed in this pilot study to inform trial design and sample size selection for a future multi-site phase II clinical trial testing anakinra as a rescue treatment for moderate asthma exacerbations.

Подробное описание

This pilot study will incorporate early intervention with the IL-1 receptor antagonist (IL-1RA), anakinra, as part of a home-based asthma action plan (AAP) at the start of a moderate exacerbation with the goal of preventing severe exacerbations requiring systemic steroids. The investigators will determine the feasibility of recruitment, enrollment, and retention for a trial that requires self administered injections; adherence to critical protocol operational tasks and rates of moderate exacerbations; and preliminary safety and efficacy of anakinra treatment during a moderate asthma exacerbation, with the goal of these findings supporting the development a hybrid decentralized phase II trial.

40 adults (≥18 years and \< 65 years) with persistent asthma that experienced an exacerbation within the prior 12 months requiring systemic steroid treatment will be enrolled, with the aim to randomize 20 women and 20 men. Up to 100 subjects will be screened to randomize 40 subjects.

Patients are to receive anakinra or placebo during a moderate asthma exacerbation (defined by pre-specified criteria). Investigators will monitor symptom scores, lung function measurements, rescue medication use, systemic corticosteroid use, and healthcare utilization during exacerbations. Device training, blood collection, and nasal sample collection will also occur.

Вмешательства

• Препарат Anakinra 100 Mg/0.67 Ml Inj Syringe
  Active study treatment
• Препарат Saline Placebo/0.67 Ml Inj Syringe
  Placebo

Первичные конечные точки

• Effect of Anakinra on absolute change in morning PEF from baseline during moderate asthma exacerbation [Срок оценки: Day 1 of treatment through day 10 after treatment]
• Study Design Feasibility - Percentage of participants who experience one moderate asthma exacerbation [Срок оценки: The 6-month period from randomization to the end of study visit]

Вторичные конечные точки (12)

• Effect of Anakinra on Asthma Index during moderate asthma exacerbation [Срок оценки: Day 1 of treatment to day 10 after treatment]
• Intervention Feasibility - Mean number of participants enrolled per month [Срок оценки: 18 months]
• Intervention Feasibility - Mean number of participants randomized per month [Срок оценки: 18 months]
• Intervention Feasibility - Percentage of participants retained through completion of study [Срок оценки: 24 months]
• Study Design Feasibility - Percentage of participants completing daily PEF measurements [Срок оценки: 24 months]
• Fidelity to Study Intervention - Percentage of prescribed doses of study treatment that are self-administered by the participant [Срок оценки: 24 months]
• Percentage of participants requiring rescue systemic corticosteroid treatment [Срок оценки: The 10 day period following the start of treatment for an exacerbation]
• Percentage of participants with rebound worsening of asthma exacerbation after study treatment [Срок оценки: The 10 day period following the start of treatment for an exacerbation]
• Percentage of participants experiencing an asthma exacerbation that requires emergency care [Срок оценки: The 10 day period following the start of treatment for an exacerbation]
• Percentage of participants experiencing an asthma exacerbation that requires hospitalization. [Срок оценки: The 10 day period following the start of treatment for an exacerbation]
• Percentage of participants with post-treatment severe neutropenia. [Срок оценки: 14 days following the start of treatment for an exacerbation]
• Percentage of participants experiencing serious infection [Срок оценки: The 14 day period following the start of treatment for an exacerbation]

Критерии участия

Критерии включения

• Provision of signed and dated informed consent form
• Age ≥18 years
• A history of physician-diagnosed persistent asthma or symptoms consistent with persistent asthma based on national or international guidelines for diagnosis and management of asthma.
• Current use of controller therapy such as inhaled corticosteroid (ICS) or ICS in combination with long-acting beta agonist (LABA)
• Asthma exacerbation requiring systemic corticosteroid therapy in the past 12 months
• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy or who have been amenorrheic for 12 months or more.
• Asthma Impairment and Risk Questionnaire (AIRQ) Score >2

Критерии исключения

• Clinical contraindications:

• Physician diagnosis of other chronic pulmonary disease including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema or congenital disorders of the lungs or airways.
• History of undergoing bronchial thermoplasty.
• Intubation for asthma in the last 12 months
• History of malignancy except non-melanoma skin cancer within the last five years.
• Any chronic medical condition considered by the PI as a contraindication to inclusion in the study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic or recurrent infections or immunodeficiency.
• Mental illness or history of substance abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• History of smoking: i. Smoking >1 time per week in the past year; ii. If ≥40 years old: Smoked ≥15 pack years; iii. If <40 years old: Smoked ≥10 pack years; iv. Smoking equivalents of 1 pack cigarettes a day for 1 year: 1 cigar or pipe daily for 1 year; Hookah - 1 session per day for 1 year; E-cigarettes or vapes - 1 cartridge/tank/pod per day for 1 year; and active use of smoking/vaping marijuana, specified as once per week in the last year.
• Allergy/sensitivity to study drugs or their formulations, including latex
• Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
• Current participation in an interventional trial in which study administration was administered within the past 60 days or within 5 half-lives of the drug (whichever is greater)
• Pregnancy, plans to get pregnant or nursing a baby. Female volunteers will be asked to use effective birth control (stable regimen of hormonal contraceptive use for at least 6 months, intrauterine device placement, or tubal ligation for at least 6 months through at least one week after study completion) and will provide a urine sample to test for pregnancy on study days. If the test is positive or the participant has reason to believe she may be pregnant, she will be dismissed from the study. Women who have been amenorrheic for 12 months may participate. Male volunteers will be asked to use condoms for the duration of the study through at least one week after study completion.
• Usage of the following medications:

• Use of daily systemic corticosteroid therapy for asthma control
• Use of any immunomodulatory therapy within the preceding 12 months, including biologics that are approved for asthma.
• Currently receiving allergen immunotherapy
• Use of any immunosuppressant therapy within the preceding 12 months will be reviewed by the study physician.
• Laboratory: Participants who meet the following criteria will be excluded from study:

• Positive QuantiFERON-tuberculosis (TB) gold assay. Cases of indeterminate QuantiFERON-TB test results will require a second specimen to be drawn.
• Baseline absolute neutrophil count (ANC) <1.0 x 109/L for participants of African descent, <1.5 x 109/L for other participants
• Allergy/sensitivity to study drugs or their formulations, including latex.
• History of anaphylaxis requiring epinephrine treatment
• Inability or unwillingness of a participant to give written informed consent.
• Inability or unwillingness to self-administer injectable medication (anakinra or placebo).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of North Carolina Chapel Hill — Chapel Hill

Идентификаторы

NCT: NCT07600190 · 25-1995 · R34HL179910

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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