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

NCT02237196 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: DAIT ITN057ADCATNIP
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Cat Allergy; Cat Hypersensitivity

Keywords

cat-allergic; cat immunotherapy; anti-thymic stromal lymphopoietin (anti-TSLP)

Outcome Measures

Primary Outcomes (1)

• Total Nasal Symptom Score (TNSS) Area Under the Curve (AUC)

  TNSS (0-12) is a participant rated score computed as the sum of four subscale scores (0-3) measuring nasal congestion and blockade, rhinorrhea, itching, and sneezing. Participants indicate a score on each subscale of 0, 1, 2, or 3, indicating none, mild, moderate, or severe symptoms, respectively. Higher scores indicate more severe nasal symptoms. The trapezoidal rule was used to calculate the TNSS AUC. The primary outcome compared the mean TNSS AUC from 0 to 1 hour after cat Nasal Allergen Challenge at 104 weeks by treatment group, using a longitudinal repeated measures model in the ITT sample. The model included fixed effects for treatment, time, and treatment by time interaction and included covariates for site, baseline TNSS AUC and Baseline Cat exposure (low vs high). The primary endpoint was assessed at week 104 using a contrast in least squares means between the following groups: AMG 157+Cat Immunotherapy and AMG 157 Placebo+Cat Immunotherapy.

  0 to 1 hour of the NAC at Week 104

Secondary Outcomes (8)

• Skin Prick Test Endpoint Titration

  15 minutes after Time 0 of the skin prick titration test at: Baseline (Week 0) and Weeks 1, 4, 12, 26, 52, 78 and 104

• Skin Early Phase Response (EPR) to Intradermal Testing

  15 minutes after Time 0 of the intradermal test at: Baseline (Week 0) and Weeks 26, 52, and 104

• Skin Late Phase Response (LPR) to Intradermal Testing

  6 hours status post cat allergen challenge at: Baseline (Time 0) and Weeks 26, 52 and 104

• Peak Total Nasal Symptom Score (TNSS): Early Phase Response (EPR)

  0 to 1 hour of the NAC at: Baseline (Week 0) and Weeks 26, 52, 78 and 104

• Total Nasal Symptom Score (TNSS) Early Phase Response (EPR)

  0 to 1 hour of the NAC at: Baseline (Week 0) and Weeks 26, 52, 78 and 104

Study Arms (4)

AMG 157+Cat Immunotherapy

EXPERIMENTAL

AMG 157 will be administered every four weeks. Cat immunotherapy will be administered weekly.

Biological: AMG 157; Biological: Cat Immunotherapy

AMG 157 Placebo+Cat Immunotherapy

ACTIVE COMPARATOR

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

Biological: Cat Immunotherapy; Biological: AMG 157 Placebo

AMG 157+Cat Immunotherapy Placebo

EXPERIMENTAL

AMG 157 will be administered every four weeks. Placebo for Cat immunotherapy will be administered weekly.

Biological: AMG 157; Biological: Cat Immunotherapy Placebo

Placebo-Placebo

PLACEBO COMPARATOR

Placebo for AMG 157 will be administered every four weeks. Placebo for cat immunotherapy will be administered weekly.

Biological: Cat Immunotherapy Placebo; Biological: AMG 157 Placebo

Interventions

AMG 157 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.

Also known as: MEDI9929/AMG 157

AMG 157+Cat Immunotherapy; AMG 157+Cat Immunotherapy Placebo

Cat Immunotherapy BIOLOGICAL

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

Also known as: Cat Allergen Extract

AMG 157 Placebo+Cat Immunotherapy; AMG 157+Cat Immunotherapy

Cat Immunotherapy Placebo BIOLOGICAL

Placebo for allergen-specific immunotherapy administered subcutaneously

Also known as: Placebo for Cat Immunotherapy

AMG 157+Cat Immunotherapy Placebo; Placebo-Placebo

AMG 157 Placebo BIOLOGICAL

Placebo for AMG 157 administered intravenously

Also known as: Placebo for AMG157

AMG 157 Placebo+Cat Immunotherapy; Placebo-Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (9)

University of California, Los Angeles

Los Angeles, California, 90025, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Asthma & Allergy Center

Baltimore, Maryland, 21231, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, 74136, United States

Location

ASTHMA Inc. Clinical Research Center

Seattle, Washington, 98115, United States

Location

University Wisconsin, Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 36223848 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Immune Tolerance Network (ITN) Website
• World Allergy Organization (WAO) Subcutaneous Immunotherapy Systemic Reaction Grading System

MeSH Terms

Interventions

tezepelumab

Limitations and Caveats

None listed

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Jonathan Corren, MD

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 11, 2014
• Study Start: March 3, 2015
• Primary Completion: March 4, 2019
• Study Completion: March 4, 2019
• Last Updated: May 6, 2020
• Results First Posted: May 6, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (9)