Clinical Trials Register

Summary
EudraCT Number:	2020-000585-41
Sponsor's Protocol Code Number:	OG-061-01
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-05-15
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2020-000585-41

A.3

Full title of the trial

Effects of tregalizumab on allergen-induced airway responses and airway inflammation in asthmatic patients

Effekte von Tregalizumab auf allergen-induzierte Atemwegsreaktionen und Atemwegsentzündung bei Patienten mit Asthma

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical study to investigate tregalizumab effects on allergen-induced airway responses and airway inflammation in asthmatic patients

A.3.2

Name or abbreviated title of the trial where available

Tregulaire

A.4.1

Sponsor's protocol code number

OG-061-01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	T-Balance Therapeutics GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	T-Balance Therapeutics GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	T-Balance Therapeutics GmbH
B.5.2	Functional name of contact point	T-Balance Therapeutics GmbH
B.5.3	Address:
B.5.3.1	Street Address	Waldfriedstrasse 4
B.5.3.2	Town/ city	Frankfurt a. Main
B.5.3.3	Post code	60528
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 69 666 8382

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tregalizumab 100 mg/mL
D.3.2	Product code	BT061
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TREGALIZUMAB
D.3.9.2	Current sponsor code	BT061
D.3.9.4	EV Substance Code	SUB189005
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	a humanized IgG1 monoclonal antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Provokit® 0,33%
D.2.1.1.2	Name of the Marketing Authorisation holder	Aristo Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Provokit® 0,33%
D.3.4	Pharmaceutical form	Powder and solvent for nebuliser solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHACHOLINE CHLORIDE
D.3.9.1	CAS number	62-51-1
D.3.9.4	EV Substance Code	SUB08832MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	33
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

mild controlled allergic asthma and house-dust mite (HDM) allergy

E.1.1.1

Medical condition in easily understood language

allergic asthma and house-dust mite allergy

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10001705
E.1.2	Term	Allergic asthma
E.1.2	System Organ Class	100000004855

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020419
E.1.2	Term	House dust mite allergy
E.1.2	System Organ Class	100000004870

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

•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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 barrier method, contraceptive patch or female sterilization) during the study and for at least 3 months after the last administration of study drug
OR
Non-vasectomized man who, during the study or in the 3 months after the last administration of study drug, is not using two (2) independent effective contraceptive methods (as specified above) or is planning a sperm donation.
31.Donation of blood within 30 days prior to screening until end of study.
32.Participation in another clinical trial within 90 days before screening or during the study.
33.Inability or lacking motivation to adhere to the study requirements and to comply with the study schedule.
34.Imprisonment or placement in an institution (AMG § 40 (1), sentence 4).

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 2, Visit 4 and visit 17

E.5.2

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 activation markers, e.g., CTLA-4, LAP, CD137, CD154 (optional);
• Anti-SARS-CoV-2-S antibody levels.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 1 to Visit 19

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

In case of any abnormal findings on the occasion of the follow-up visit that were assessed as clinically significant or alarming by the investigator, subjects will be invited for further medical investigations for safety reasons.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-11-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-01-12

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