Effects of Anti-TSLP in Patients With Asthma

NCT02698501 | Completed Phase 2

• 1 other identifier: ESR-15-10870
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether anti-TSLP will decrease airway hyperresponsiveness in patients with asthma already on daily treatment with inhaled corticosteroids. The investigators expect that airway hyperresponsiveness will decrease after treatment with anti-TSLP, and that this happens due to a change in the type of mast cells with in the lungs. Also, the investigators expect a decrease in inflammatory cells and mediators measured in material from the lungs. Half of the participants will receive anti-TSLP (MEDI9929) on top of their regular asthma treatment, while the other half will receive placebo on top of their regular asthma treatment.

Conditions

Asthma

Keywords

Asthma; Airway hyperresponsiveness; TSLP; Mast cell; Eosinophil

Outcome Measures

Primary Outcomes (4)

• Decrease in airway hyperresponsiveness to mannitol in response to treatment with MEDI9929 in patients with asthma

  Change in PD15 to mannitol (provoking dose for 15% reduction in FEV1, expressed as doubling doses) measured at baseline and after the 12-week treatment period between groups.

  12 weeks

• Supportive primary objective 1: Mannitol test negative in response to treatment with MEDI9929 in patients with asthma

  Number of mannitol test negative (PD15 \> 635mg) subjects after a 12-week treatment period between groups

  12 weeks

• Supportive primary objective 2: Decrease in airway hyperresponsiveness to mannitol in response to treatment with MEDI9929 in patients with asthma

  The change in PD15 to mannitol measured at baseline and after the 12-week treatment period, expressed as geometric mean calculated by linear interpolation, compared between treatments.

  12 weeks

• Supportive primary objective 3: Decrease in airway hyperresponsiveness to mannitol in response to treatment with MEDI9929 in patients with asthma

  Change in RDR (Response Dose Ratio) to mannitol measured at baseline and after the 12-week treatment period between groups

  12 weeks

Secondary Outcomes (4)

• Change in number of Chymase/CPA-3 positive mast cells following treatment with MEDI9929

  12 weeks

• Changes in percentage of airway eosinophils and neutrophils in sputum in patients treated with MEDI9929 compared to placebo.

  12 weeks

• Changes in percentage of airway eosinophils and neutrophils in airway submucosa in patients treated with MEDI9929 compared to placebo.

  12 weeks

• Changes in number of airway eosinophils and neutrophils in blood in patients treated with MEDI9929 compared to placebo.

  12 weeks

Other Outcomes (14)

• Change in diversity in airway microbiota in patients treated with MEDI9929 compared to placebo

  12 weeks

• Change in airway microbiota in patients treated with MEDI9929 compared to placebo

  12 weeks

• The effect of MEDI9929 on TSLP mRNA expression

  12 weeks

Study Arms (2)

MEDI9929

EXPERIMENTAL

MEDI9929 is a human monoclonal antibody immunoglobulin IgG2λ directed against TSLP. MEDI9929 binds with human TSLP and prevents its interaction with thymic stromal lymphopoietin receptor (TSLPR).

Drug: MEDI9929

Placebo

PLACEBO COMPARATOR

Apart from the active substance, the placebo is otherwise identical to IMP.

Drug: Placebo

Interventions

MEDI9929 DRUG

MEDI9929 700mg (3 doses in total, 4-week intervals), administered intravenously

MEDI9929

Placebo DRUG

Placebo (3 doses in total, 4-week intervals), administered intravenously

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age 18 through 75, inclusive at the time of Visit 1
• Body mass index between 18-40 kg/m2 (both inclusive) and weight ≥ 40 kg at Visit 1.
• A diagnosis of asthma as defined by GINA (ginasthma.org).
• ICS (in any dose) on a daily basis for at least three months prior to Visit 1
• A stable asthma controller regimen with ICS (±LABA) for at least 4 weeks prior to Visit 1
• A FEV1 value of ≥ 70% at Visit 1
• ACQ-6 \> 1 (partly controlled) at Visit 1
• PD15 to mannitol \<= 315 mg at visit 1
• Subjects must demonstrate acceptable inhaler and spirometry techniques during screening (as evaluated and in the opinion of study site staff)
• Subjects must demonstrate ≥ 70% compliance with usual asthma controller ICS±LABA during the screening (V1 to V3).

You may not qualify if:

• Current smokers or subjects with a smoking history of ≥ 10 pack years. Former smokers with \< 10 pack years must have stopped for at least 6 months to be eligible.
• Previous medical history or evidence of an uncontrolled intercurrent illness.
• Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results.
• Clinically relevant abnormal findings in hematology or clinical chemistry.
• Evidence of active liver disease.
• History of cancer.
• Acute upper or lower respiratory infections.
• Helminth parasitic infection.
• Known history of active tuberculosis (TB).
• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology.
• A positive human immunodeficiency virus (HIV) test.
• History of sensitivity to any component of the investigational product.
• History of anaphylaxis to any biologic therapy.
• History of documented immune complex disease (Type III hypersensitivity reactions) to mAb administration.
• History of any known primary immunodeficiency disorder.

Sponsors & Collaborators

• Celeste Porsbjerg: lead
• Lund University: collaborator
• University of Newcastle, Australia: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Copenhagen University Hospital Bispebjerg

Copenhagen, 2400, Denmark

Location

Related Publications (1)

• Sverrild A, Hansen S, Hvidtfeldt M, Clausson CM, Cozzolino O, Cerps S, Uller L, Backer V, Erjefalt J, Porsbjerg C. The effect of tezepelumab on airway hyperresponsiveness to mannitol in asthma (UPSTREAM). Eur Respir J. 2021 Dec 31;59(1):2101296. doi: 10.1183/13993003.01296-2021. Print 2022 Jan. No abstract available.

  PMID: 34049943 DERIVED

MeSH Terms

Conditions

Asthma; Respiratory Hypersensitivity

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Celeste Porsbjerg, MD, PhD

  Copehagen University Hospital Bispebjerg, Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, PhD

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: March 3, 2016
• Study Start: August 1, 2016
• Primary Completion: August 7, 2019
• Study Completion: October 7, 2019
• Last Updated: June 2, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)