Anakinra as a Rescue Treatment for Allergic Inflammation

NCT04035109 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 18-26505R01HL135235
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Asthma, Allergic

Keywords

asthma; nasal allergy; house dust mite; cat

Outcome Measures

Primary Outcomes (1)

• Change in eosinophils per milliliter of Nasal Lavage Fluid (NLF)

  Allergen-induced eosinophil recruitment will be measured by measuring eosinophil content of fluid obtained from lavage of the nares, comparing pre-challenge lavage samples to samples obtained 6 hours after allergen challenge

  6 hours post-allergen challenge versus pre-allergen challenge

Secondary Outcomes (6)

• Change in neutrophils per milliliter of NLF

  6 hours post-allergen challenge versus pre-allergen challenge

• Change in inflammatory cytokines in nasal epithelial lining fluid (ELF)

  6 hours post-allergen challenge versus pre-allergen challenge

• Change in secreted mucin, MUC5AC, in NLF

  6 hours post-allergen challenge versus pre-allergen challenge

• Change in secreted mucin, MUC5B, in NLF

  6 hours post-allergen challenge versus pre-allergen challenge

• Change in Nonspecific bronchial reactivity (NSBR)

  24 hours post-allergen challenge versus pre-allergen challenge

Study Arms (2)

Anakinra (Period 1) then Placebo (Period 2)

OTHER

Subjects randomized to this arm will receive a single injection of anakinra 1 mg/kg (max dose of 100 mg) administered subcutaneously after their first allergen challenge (Period 1), followed by the matching saline placebo after their second allergen challenge (Period 2).

Drug: Anakinra; Drug: Preservative-free 0.9% sodium chloride (Placebo); Biological: House dust mite allergen; Biological: Cat hair allergen

Placebo (Period 1) then Anakinra (Period 2)

OTHER

Subjects randomized to this arm will receive a single injection of saline placebo administered subcutaneously after their first allergen challenge (Period 1), followed by anakinra 1 mg/kg (max dose of 100 mg) administered subcutaneously after their second allergen challenge (Period 2).

Drug: Anakinra; Drug: Preservative-free 0.9% sodium chloride (Placebo); Biological: House dust mite allergen; Biological: Cat hair allergen

Interventions

Anakinra DRUG

A single 1mg/kg subcutaneous injection (up to 100mg) of anakinra will be administered after nasal allergen challenge.

Also known as: Kineret

Anakinra (Period 1) then Placebo (Period 2); Placebo (Period 1) then Anakinra (Period 2)

Preservative-free 0.9% sodium chloride (Placebo) DRUG

A single subcutaneous injection of sodium chloride (placebo) will be administered after nasal allergen challenge.

Anakinra (Period 1) then Placebo (Period 2); Placebo (Period 1) then Anakinra (Period 2)

House dust mite allergen BIOLOGICAL

Standardized house dust mite (Dermatophagoides farinae) allergen extract (provided by Greer Laboratories, Lenoir, NC). Participants who are sensitized to house dust mite (determined by skin prick testing) will undergo intranasal challenge with house dust mite allergen extract. All participants will undergo allergen challenge with a single allergen (house dust mite or cat hair).

Also known as: Dermatophagoides farinae

Anakinra (Period 1) then Placebo (Period 2); Placebo (Period 1) then Anakinra (Period 2)

Cat hair allergen BIOLOGICAL

Standardized cat hair allergen extract (provided by Greer Laboratories, Lenoir, NC). Participants who are sensitized to cat hair (determined by skin prick testing) will undergo intranasal challenge with cat hair allergen extract. All participants will undergo allergen challenge with a single allergen (house dust mite or cat hair).

Also known as: Felis catus

Anakinra (Period 1) then Placebo (Period 2); Placebo (Period 1) then Anakinra (Period 2)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

MeSH Terms

Conditions

Asthma

Interventions

Interleukin 1 Receptor Antagonist Protein; Sodium Chloride; Antigens, Dermatophagoides

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Antigens

Study Officials

• Michelle Hernandez

  Associate Professor of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Anakinra and matching saline placebo will be provided by the investigational drug service
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 29, 2019
• Study Start: December 16, 2019
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2023
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 9 to 36 months following publication
• Access Criteria: Approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and execution of a data use/sharing agreement with UNC.