Late Phase Administration Anakinra as a Rescue Treatment for Inhaled Allergen Challenge-Induced Airway Inflammation

• Status: Withdrawn
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Purpose: The primary objective of this study is to examine the effectiveness of anakinra as a rescue treatment for allergic airway inflammation. Utilizing an inhaled allergen challenge model, the investigators will determine the effectiveness of a single 1 mg/kg dose of anakinra administered after inhaled allergen challenge for mitigating features of airway inflammation.

Participants: 25 mild allergic asthmatics sensitized to Dermatophagoides farinae (D. farinae) Procedures (methods): 12 eligible subjects of 25 volunteers will participate in a double blind cross-over study. Following randomization to the placebo or anakinra treatment group, subjects will undergo inhalation of D. farinae, and their early and late phase asthmatic responses will be measured. Subjects will undergo induced sputum sampling, methacholine challenge, and mucociliary clearance measures. After completion of period 1, subjects will cross over to the alternate study arm.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

• Age range 18-45 years, inclusive

• FEV1 of at least 80% of predicted and FEV1/FVC (forced vital capacity) ratio of at least 0.7 (without use of bronchodilator medications for 12 hours or long acting beta agonists for 24 hours), consistent with lung function of persons with no more than mild episodic or mild persistent asthma.

• Physician diagnosis of asthma

• Positive methacholine inhalation challenge as performed in the separate screening protocol within the prior 12 months (defined as provocative concentration of methacholine of 10 mg/mL or less producing a 20% fall in FEV1 (PC20 methacholine)

• Allergic sensitization to house dust mite (D. farinae) as confirmed by positive immediate skin prick test response

• Clinical reactivity to D. farinae assessed through inhaled allergen challenge with a decline in FEV1 of ≥20% from baseline in the early asthmatic response and ≥15% in the late asthmatic response.

• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy or who have not been amenorrheic for 12 months or more.

• Oxygen saturation of >94% and blood pressure within the following limits: (Systolic between 150-90 mmHg, Diastolic between 90-60 mmHg).

• Ability to provide an induced sputum sample.

• Negative intracutaneous tuberculin skin test (PPD) defined as less than 5mm induration for the purpose of this protocol (positive PPD contraindication to anakinra injection). A negative tuberculosis (TB) test within the past year (either PPD or quantiferon TB Gold) is also acceptable

Exclusion Criteria:

Clinical contraindications:

• Any chronic medical condition considered by the PI as a contraindication to participation in the study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections or immunodeficiency.

• Pregnancy or nursing a baby

• History of latex allergy/sensitivity

• Allergy/sensitivity to anakinra or its formulation

• Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.

• Exacerbation of asthma more than 2x/week which could be characteristics of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.

• Daily requirements for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma (not to include prophylactic use of albuterol prior to exercise).

• Viral upper respiratory tract infection within 4 weeks of challenge.

• Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.

• Severe asthma

• Mental illness of history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

• Cigarette smoking >1 pack per month

• Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.

• Allergy/sensitivity to study drugs or their formulations

• Known hypersensitivity to methacholine or to other parasympathomimetic agents

• History of intubation for asthma

• Unwillingness to limit coffee, tea, cola drinks, chocolate, or other foods containing caffeine after midnight on the days that methacholine challenge testing and inhaled allergen challenge is to be performed

• Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).

• Radiation history will be collected. Any subject whose exposure history within the past twelve months would cause them to exceed their annual limits will be excluded

Usage of the following medications:

• Use of systemic steroid therapy within the preceding 12 months for an asthma exacerbation. All use of systemic steroids in the last year will be reviewed by a study physician.

• Subjects who are prescribed daily inhaled corticosteroids, cromolyn, or leukotriene inhibitors (Montelukast or Zafirlukast) will be required to discontinue these medications at least 4 weeks prior to their screening visit.

• Use of daily theophylline within the past month.

• Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).

• Use of any immunosuppressant therapy within the preceding 12 months will be reviewed by the study physician.

• Use of any immunomodulatory therapy within the preceding 12 months.

• Use of beta blocking medications

• Antihistamines in the 5 days prior to allergen challenge

• Routine use of NSAIDs, including aspirin.

Physical/laboratory indications:

• Abnormalities on lung auscultation

• Temperature >37.8 C

• Oxygen saturation of <94%

• Systolic BP>150 mmHg or <90 mmHg or diastolic BP>90 mmHg or <60 mmHg

• Absolute neutrophil count <1.4 x 109/L

Inability or unwillingness of a participant to give written informed consent