Anakinra as a Rescue Treatment for Allergic Inflammation

• Status: Suspended
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Participants with mild asthma who are sensitized to either house dust mite or cat hair allergen will undergo nasal instillation of the allergen to elicit nasal allergy symptoms. The participants will be treated in a cross-over fashion with either placebo (saline) or anakinra to determine if anakinra will reduce nasal airway eosinophil recruitment, eosinophil activation, release of inflammatory mediators, mucins, and gene expression changes in epithelial cells.

• 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:

• Males and females ages 18-45 years, inclusive

• Subjects will have mild asthma characterized by a Forced Expiratory Volume in 1 second (FEV1) of at least 75% of predicted and FEV1/FVC (Forced Vital Capacity) ratio of at least .60 (without use of bronchodilator medications for 12 hours), consistent with lung function of persons with mild episodic or mild persistent asthma. For the purpose of this protocol, an asthmatic individual will be defined as having a) positive methacholine challenge with a provocative concentration (PC) of methacholine producing a 20% fall in FEV1 (Provocative Concentration to decrease FEV1 by 20% (PC20) methacholine) with less than or equal to 10 mg/ml; OR b) physician-diagnosed asthma.

• OR non-asthmatic individuals with allergic rhinitis

• Allergic sensitization to house dust mite (Dermatophagoides farinae) OR cat (Felis catus) as confirmed by positive immediate skin prick test response (identified previously on a general screening visit)

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

• Ability to withhold antihistamine medications for one week prior to baseline and allergen challenge visits.

• Negative quantiferon gold TB test positive tuberculosis (TB) test is a contraindication to anakinra injection). A negative TB test within the past year (either tuberculin skin test (TST) with less than 5 mm induration or negative quantiferon TB Gold) is also acceptable.

• Subjects must be able and willing to give informed consent.

Exclusion Criteria:

• 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 or 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 nasal allergen challenge is to be performed.

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

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 non-steroidal anti-inflammatory drugs (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 (ANC) <1.4 x 109/L