mild controlled allergic asthma and house-dust mite (HDM) allergy MedDRA version: 21.1 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 100000004855 MedDRA version: 20.0 Level: LLT Classification code 10020419 Term: House dust mite allergy System Organ Class: 100000004870
Conditions
Interventions
Product Name: Tregalizumab 100 mg/mL
Product Code: BT061
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TREGALIZUMAB
Current Sponsor code: BT061
Concentration unit: mg/ml milligram(s
Sponsors
T-Balance Therapeutics GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Willing and able to give written informed consent 2.Male or female subject aged 18 to 65 years (both inclusive). 3.Established diagnosis of mild controlled allergic asthma (GINA 2019) and history of allergic bronchial asthma for at least 1 year. 4.Body mass index (BMI) of 18.0 to 30.0 (both inclusive). 5.Non-smoker (all substances). 6.Specific IgE to HDM (Dermatophagoides farinae) = class 2 in radioallergosorbent test (RAST). 7.BHR (i.e., a decrease in FEV1 of at least 20%) measured by methacholine challenge. 8.FEV1 = 75% of predicted value (according to height, weight and sex). 9.Subject must demonstrate a significant EAR and LAR without rescue medication use within the first 7 hours after BAP. EAR is defined as a decrease in FEV1 of = 20% within 0 to 3 hours after allergen challenge; LAR is defined as a decrease in FEV1 of = 15% within 4 to 7 hours after BAP. 10. No clinically relevant abnormalities in 12-lead ECG at screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Severe, unstable bronchial asthma. 2.Exacerbation of asthma = 4 weeks prior to screening. 3.Treatment with parenteral and oral corticosteroids 6 weeks prior to screening and during the study. 4.Treatment with inhaled corticosteroids, methylxanthines (e.g., theophyllin), anticholinergics (e.g., ipratropium bromide), leukotriene modifiers (e.g., montelukast), tiotropium bromide, cromolyn or nedocromil within 2 weeks prior to screening and during the study. 5.Current treatment with any immunosuppressants (e.g., monoclonal antibodies, methotrexate, cyclosporin). 6.Specific immunotherapy (SCIT) to mite within 3 years prior to screening. 7.Serious adverse drug reaction to previous biological treatment. 8.Previous therapy with a monoclonal antibody (mAb) targeting CD4, including tregalizumab. 9.Known hypersensitivity to any constituents of tregalizumab, and/or other mAbs, that, in the opinion of the investigator or Medical Monitor, contraindicates participation. 10.Previous inclusion in this study. 11.Serum transaminases, alanine transaminase (ALAT) and/or aspartate transaminase (ASAT) > 2.5-fold upper level of normal (ULN) at screening. 12.Bilirubin > 34.2 µmol/L at screening. 13.Alkaline phosphatase (AP) > 2-fold ULN at screening. 14.Urea nitrogen > 1.5-fold ULN at screening. 15.Kidney insufficiency as defined by creatinine level > 133 µmol/L at screening. 16.History of severe allergic or anaphylactic reaction to proteins of human origin (e.g. vaccination reaction, biological therapy). 17.Presence or history of malignancy within the previous 5 years (except completely resected squamous or basal cell carcinoma of the skin). 18.Presence or history of clinically significant major disease (e.g., severe heart/lung disease New York Heart Association [NYHA] Class = 3, autoimmune disease [apart from rheumatoid arthritis], acute uncontrolled hyper- or hypo-thyroidism, severe uncontrolled hypo or hypertension). 19.Serious local (e.g., abscess) or systemic (e.g., pneumonia, septicemia) infection or recurrent chronic infections within 6 weeks prior to screening visit or during the screening period. 20.Any infection requiring antibiotic therapy by any route of administration within 4 weeks prior to screening. 21.Vaccination with live, live attenuated, and/or killed vaccines in the 12 weeks prior to the first administration of the study drug and during the study. 22.Positive diagnosis for acute or chronic infections (e.g. Hepatitis C Virus [HCV], Hepatitis B Virus [HBV], Human Immunodeficiency Virus [HIV]) at screening or history of previous chronic infection. 23.Acute or clinically symptomatic Epstein-Barr Virus (EBV) (infectious mononucleosis) or Cytomegalovirus (CMV) infection. 24.Presence or history of latent or active tuberculosis. 25.Known immune deficiency. 26.Presence or history of lymphoproliferative disease, including lymphoma and lymphadenopathy. 27.Presence or history of clinically significant drug or alcohol abuse. 28.Employee at study site or any institution involved in this study (including the sponsor), or spouse/partner or relative of an investigator. 29.Pregnant or nursing woman or woman considering to become pregnant during the study or in the 3 months after the last administration of study drug. 30.Woman of childbearing potential (unless surgically sterile or post-menopausal > 52 weeks) who is not using two (2) independent effective contraceptive methods (e.g., oral or injectable contraceptives, intra-uterine devices, double barrie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to investigate the effect of 100 mg tregalizumab treatment administered weekly (via subcutaneous injection) over 12 weeks to patients with mild controlled allergic asthma and HDM allergy, who have been exposed to allergen induced bronchoconstriction under controlled conditions in this challenge study. The primary endpoint supporting this objective will be the change from baseline in the Late Asthmatic Response (LAR) after BAP;Secondary Objective: •Evaluate the Early Asthmatic Response (EAR) after BAP in adult patients with mild controlled allergic asthma and HDM allergy over 12-week treatment with tregalizumab. •Determine the anti-inflammatory profile of tregalizumab on the airways in induced sputum, by exhaled nitric oxide (eNO) and in blood after 12-week treatment with tregalizumab; •Examine bronchial hyperresponsiveness (BHR) after a methacholine inhalation challenge after 12-week treatment with tregalizumab ; •Determine the pharmacodynamics by CD4 modulation, the pharmacokinetics and immunogenicity of tregalizumab treatment; •Assess the safety and tolerability of tregalizumab; •Assess the effect of tregalizumab treatment on the asthma-related quality of life. ;Primary end point(s): The primary endpoint will be the baseline-corrected LAR measured by the area under the curve (AUC) for FEV1 at 4 to 7 hours after BAP (AUC4-7FEV1) on Day 84. The AUC4 7FEV1 will be calculated as the area under the curve of the normalized FEV1 values (post-BAP FEV1 values divided by the pre-BAP FEV1 value in %) over time;Timepoint(s) of evaluation of this end point: Visit 2, Visit 4 and visit 17 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change in LAR on Day 84, as measured from 4 to 7 hours after BAP by the maximum decrease in the normalized FEV1 values; •Change in EAR on Day 84, as measured from 0 to 3 hours after BAP by the maximum decrease in the normalized FEV1 values; •Change in EAR on Day 84, as measured from 0 to 3 hours after BAP by the AUC of the normalized FEV1 values; •Fraction of eNO (FeNO) absolute levels and delta increase after BAP; •Dose of methacholine causing a decrease in FEV1 of at least 20% (methacholine PD20); •Impact of tregalizumab on TH1, TH2 and TH17 cytokines in serum and sputum and its correlation to LAR in tregalizumab-treated subjects in comparison to placebo; •Impact of tregalizumab on known markers of TH2-induced inflammation (total IgE, mite-specific IgE, eosinophils) and eNO in tregalizumab-treated subjects in comparison to placebo after 12 weeks; •Mite-specific IgG4 and total IgG after 12 weeks; •Induced sputum markers: oEosinophils, neutrophils, macrophages and lymphocytes in cytospin samples oTH1, TH2 and TH17 cytokines oPCR for TH1, TH2 and TH17 cytokines and T-cell transcription factors oEosinophil cationic protein (ECP) •Impact of tregalizumab on the expression of markers of PBMC lineage; •Safety evaluations include the incidence and severity of adverse events (AEs), changes in clinical laboratory profiles, and the serum levels of specific anti-tregalizumab antibodies; •Number of rescue ß2-agonist puffs ; •VAS Nasal Symptom Score at screening and 12 weeks; •Asthma-related quality of life questionnaires [Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12)] at 0 and 12 weeks. Additional/Exploratory Endpoints •Changes in miRNA expression profiles in blood in tregalizumab-treated subjects in comparison to placebo as determined by next generation sequencing (optional); •Tregalizumab trough serum levels. •Impact of tregalizumab on regulatory T-cell activation via expression of cell surface ac | — |
Countries
Germany
Contacts
Public ContactT-Balance Therapeutics GmbH
T-Balance Therapeutics GmbH
Outcome results
None listed