Anti-TSLP (AMG 157) Plus Antigen-Specific Immunotherapy for Induction of Tolerance in Individuals With Cat Allergy

NCT ID: NCT02237196

Last Updated: 2020-05-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-03

Study Completion Date

2019-03-04

Brief Summary

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This trial will test whether a novel therapeutic approach, cat immunotherapy combined with an investigational new drug called MEDI9929/AMG 157 (an anti-TSLP \[thymic stromal lymphopoietin\] antibody being co-developed by Amgen and MedImmune) can lead to lasting tolerance to cat allergen.The objective of the study is to determine whether one year of immunotherapy combined with MEDI9929/AMG 157 can induce tolerance to cat allergen.

Detailed Description

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This study will implement the concept referred to as "allergen-plus," which aims to enhance the disease-modifying mechanisms of allergen-specific immunotherapy by combining it with other anti-inflammatory or immune-modulating agents. Thymic stromal lymphopoietin (TSLP) is a cytokine which appears to be instrumental in both initiating and maintaining allergic sensitivity to antigens, and Immune Tolerance Network (ITN) investigators hypothesize that blocking TSLP during the administration of cat immunotherapy will induce durable immune changes that lead to tolerance.

CATNIP will be conducted at multiple sites in the US and enroll cat-allergic adults who will be randomized to four possible treatment groups: immunotherapy plus MEDI9929/AMG 157, immunotherapy plus placebo, placebo plus MEDI9929/AMG 157, or two corresponding placebos. This study is specifically enrolling cat allergic individuals who do not live with cats in order to limit exposure to the allergen outside of the study. Treatment will be given for about one year, followed by one year off therapy.

Conditions

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Cat Allergy Cat Hypersensitivity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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AMG 157+Cat Immunotherapy

AMG 157 will be administered every four weeks.

Cat immunotherapy will be administered weekly.

Group Type EXPERIMENTAL

AMG 157

Intervention Type BIOLOGICAL

AMG 157 will be administered once every 4 weeks at dose of 700 mg intravenously. Each AMG 157 dose will be administered at least 1 day before immunotherapy through week 24, then on the same day as immunotherapy thereafter.

Cat Immunotherapy

Intervention Type BIOLOGICAL

A standardized allergen extract licensed in the United States for allergen immunotherapy, and is formulated as a long-acting suspension for subcutaneous injection

AMG 157 Placebo+Cat Immunotherapy

Placebo for AMG 157 of similar appearance will be administered every four weeks.

Cat immunotherapy will be administered weekly.

Group Type ACTIVE_COMPARATOR

Cat Immunotherapy

Intervention Type BIOLOGICAL

A standardized allergen extract licensed in the United States for allergen immunotherapy, and is formulated as a long-acting suspension for subcutaneous injection

AMG 157 Placebo

Intervention Type BIOLOGICAL

Placebo for AMG 157 administered intravenously

AMG 157+Cat Immunotherapy Placebo

AMG 157 will be administered every four weeks.

Placebo for Cat immunotherapy will be administered weekly.

Group Type EXPERIMENTAL

AMG 157

Intervention Type BIOLOGICAL

AMG 157 will be administered once every 4 weeks at dose of 700 mg intravenously. Each AMG 157 dose will be administered at least 1 day before immunotherapy through week 24, then on the same day as immunotherapy thereafter.

Cat Immunotherapy Placebo

Intervention Type BIOLOGICAL

Placebo for allergen-specific immunotherapy administered subcutaneously

Placebo-Placebo

Placebo for AMG 157 will be administered every four weeks.

Placebo for cat immunotherapy will be administered weekly.

Group Type PLACEBO_COMPARATOR

Cat Immunotherapy Placebo

Intervention Type BIOLOGICAL

Placebo for allergen-specific immunotherapy administered subcutaneously

AMG 157 Placebo

Intervention Type BIOLOGICAL

Placebo for AMG 157 administered intravenously

Interventions

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AMG 157

AMG 157 will be administered once every 4 weeks at dose of 700 mg intravenously. Each AMG 157 dose will be administered at least 1 day before immunotherapy through week 24, then on the same day as immunotherapy thereafter.

Intervention Type BIOLOGICAL

Cat Immunotherapy

A standardized allergen extract licensed in the United States for allergen immunotherapy, and is formulated as a long-acting suspension for subcutaneous injection

Intervention Type BIOLOGICAL

Cat Immunotherapy Placebo

Placebo for allergen-specific immunotherapy administered subcutaneously

Intervention Type BIOLOGICAL

AMG 157 Placebo

Placebo for AMG 157 administered intravenously

Intervention Type BIOLOGICAL

Other Intervention Names

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MEDI9929/AMG 157 Cat Allergen Extract Placebo for Cat Immunotherapy Placebo for AMG157

Eligibility Criteria

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Inclusion Criteria

* History of moderate-severe allergic rhinitis caused by cat exposure for at least 2 yrs
* Skin prick test wheal \>/=5 mm to standardized cat extract
* Immunoglobulin E (IgE) \>/=0.7 kU/L (class 2) to cat extract
* Screening nasal allergen challenge in which:

\*TNSS is \</= 3 after the 0 concentration (vehicle control only) dose,
* TNSS increase is \</=1 from the TNSS prior to allergen administration to the TNSS after the 0 concentration (vehicle control only) dose,

* TNSS is \>/=8 after the highest dose, and
* Between the first non-zero dose and 10 minutes after the highest dose,either:
* \>/=3 sneezes are counted or
* \>20% drop in PNIF is recorded
* Body mass index (BMI) between 1 and 32 kg/m\^2, inclusive at screening
* Clinically acceptable physical examination and electrocardiogram (ECG) results (12-lead reporting RR, PR, QRS, QT and QTcF) prior to Day 0 based on the opinion of the investigator
* Adequate renal function (defined by creatinine clearance \>80 mL/min using the Cockcroft Gault equation)
* For women of childbearing age, a willingness to use a highly effective form of contraception for five months after last dose of study medication. Highly effective methods of birth control include abstinence, vasectomy by the male partner, or a condom with spermicide in combination with either hormonal birth control, IUD or barrier methods used by the woman.
* For men with female partners of childbearing potential, agreement not to donate sperm and to inform their female partner of their participation in this clinical study and use highly effective methods of birth control for five months after last dose of study medication. Highly effective methods of birth control include abstinence, vasectomy, or a condom with spermicide in combination with either hormonal birth control, Intrauterine device (IUD) or barrier methods used by the woman.
* The ability to give informed consent and comply with study procedures

Exclusion Criteria

* Prebronchodilator Forced Expiratory Volume at one second (FEV1) less than 0% of predicted value at screening visit
* History of moderate or higher Allergic Rhinitis and its Impact on Asthma (ARIA) severity classification for allergic rhinitis in the last year due to allergens other than cat
* History of asthma meeting the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 (EPR3) classification of mild-persistent or worse in the past year, other than with cat exposure, requiring regular inhaled corticosteroids for \>4 weeks per year
* History of serious chronic medical conditions which might interfere with treatment or assessments
* History of emergency visit or hospital admission for asthma in the previous 12 months
* History of chronic obstructive pulmonary disease (COPD)
* History of significant recurrent acute sinusitis, defined as 2 episodes/yr for the last 2 years, all of which required antibiotic treatment
* History of chronic sinusitis, defined as a sinus symptoms lasting \>12 weeks that includes \>/=2 major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, purulent or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness.
* History of systemic disease affecting the immune system such as autoimmune diseases, immune complex disease, or immunodeficiency, where, in the opinion of the study physician, participation in the trial would pose a risk or significant effect on the immune system
* Diabetes (Type I or II)
* Evidence of any active or suspected bacterial, viral, fungal or parasitic infection(s) within 30 days prior to randomization
* High risk of parasitic disease as judged by the investigator
* Positive QuantiFERON(R) tuberculin test UNLESS the potential subject has been treated with appropriate chemoprophylaxis
* Exposure to an individual with active tuberculosis within six months from randomization
* Subjects tested positive for HIV antibody, Hep B surface antigen, or Hep C antibody
* At randomization, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
* History of malignancy of any type, including basal cell and squamous cell cancers of the skin, within 5 years of enrollment
* Tobacco smoking (ANY) within the last year or a history of \>/=10 pack years
* Previous immunotherapy treatment with cat allergen within the previous 10 yrs
* Any history of grade 4 anaphylaxis due to any cause as defined by the CTCAE grading criteria for immunotherapy
* History of bleeding disorders or treatment with anticoagulation therapy
* Treatment with omalizumab within 6 months prior to randomization
* Currently taking any of the following medications: beta blockers; tricyclic antidepressants; monoamine oxidase inhibitors; or anti-IgE monoclonal antibody treatment
* Ongoing systemic immunosuppressive treatment
* History of intolerance to the study therapy, rescue medications, or their excipients
* For women of childbearing age a positive serum or urine pregnancy test with sensitivity of \<50 mIU/mL within 72 hours before the start of study therapy
* The use of any investigational drug within 6 months of randomization
* The presence of any medical condition that the investigator deems incompatible with participation in the trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan Corren, MD

Role: STUDY_CHAIR

University of California, Los Angeles

Locations

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University of California, Los Angeles

Los Angeles, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Johns Hopkins Asthma & Allergy Center

Baltimore, Maryland, United States

Site Status

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, United States

Site Status

ASTHMA Inc. Clinical Research Center

Seattle, Washington, United States

Site Status

University Wisconsin, Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Corren J, Larson D, Altman MC, Segnitz RM, Avila PC, Greenberger PA, Baroody F, Moss MH, Nelson H, Burbank AJ, Hernandez ML, Peden D, Saini S, Tilles S, Hussain I, Whitehouse D, Qin T, Villarreal M, Sever M, Wheatley LM, Nepom GT, Sanda S; Immune Tolerance Network ITN057AD CATNIP Study Team. Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: A randomized controlled trial. J Allergy Clin Immunol. 2023 Jan;151(1):192-201. doi: 10.1016/j.jaci.2022.08.029. Epub 2022 Oct 9.

Reference Type DERIVED
PMID: 36223848 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

http://www.immunetolerance.org/

Immune Tolerance Network (ITN) Website

https://www.aaaai.org/practice-resources/practice-tools/immunotherapy-forms/immunotherapy-systemic

World Allergy Organization (WAO) Subcutaneous Immunotherapy Systemic Reaction Grading System

Other Identifiers

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CATNIP

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT ITN057AD

Identifier Type: -

Identifier Source: org_study_id

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