Trial document





This trial has been registered retrospectively.
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  DRKS00012556

Trial Description

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Title

Optimization of the RTT method for the differentiation of patients/subjects with active or latent tuberculosis infection and non-infected patients/subjects

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Trial Acronym

LB-Y5

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URL of the Trial

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Brief Summary in Lay Language

Tuberculosis is a global bacterial infectious disease which is caused by various types of mycobacteria and which can be fatal with inadequate diagnosis and treatment. In 2015 approximately 1.4 million people died by tuberculosis (TB) according to the estimation published in 2016 by the World Health Organization (WHO). Thereby tuberculosis is one of the three most commonly fatal infectious diseases in the world. Additionally, currently are 1.7 billion people latently infected, i.e. the pathogen is in the body (due to a previous active TB infection, if applicable) but under control of the body’s own antibodies of the immune system so that there is currently no manifestation of an active affection by TB.
The quick und reliable diagnosis as well as the targeted treatment of patients with an active TB is essential for the successful treatment and containment of the disease. Latently infected people profit also by a diagnosis as up to 10 percent - especially those with a weakened immune system - bear the risk to develop an active TB in the course of their lives
Currently, it is not possible to differentiate clearly an active affection by TB from a latent TB infection. But this is of high clinical importance, as non-treatment in cases of unidentified TB infections, but also unnecessary treatment, could pose health risks for the patient. The so-called RTT TB procedure of the company Lophius Biosciences GmbH in Regensburg is able to identify patients which are infected with mycobacteria which cause TB. Additionally, it provides the possibility to differentiate between an active and a latent infection state. This procedure was already successfully used in feasibility studies.

The purpose of this study is to improve the existing RTT TB procedure further so that the attending physician can make a reliable diagnosis, preferably independent of external influences. Besides the increase of patient security, the procedure is also to be optimised so that it can be performed in a more user-friendly way in the diagnostic laboratory. The successful optimisation is part of the development of a test procedure that enables a quicker and more reliable TB diagnosis in the future.

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Brief Summary in Scientific Language

The RTT method investigated in this clinical trial represents a method for the detection of pathogen-specific immune responses and is based on the proprietary “Reverse T cell Technology”. Two feasibility studies revealed that this method allows the distinction between active/latent and non-infected subjects and between patients with active TB and subjects with latent TB-infection respectively. As the RTT method is based on blood as examination material, it could spare the patient discomfort by stressful examinations such as X-ray, sputum extraction or lymph node biopsy. Concomitantly, the infection risk for laboratory users would be reduced by avoiding handling of highly infectious sputum.
For the optimization of the RTT method, blood withdrawals are planned for patients with active TB disease or latent TB infection as well as for non-infected patients/subjects (control group). The blood volume derived from patients with active TB disease or latent TB infection as well as non-infected patients intended for tracking of therapeutic process may not exceed 50 ml. If blood donation compatibility has been confirmed by the treating physician, up to 100 ml blood may be collected from non-infected subjects.
The max. number of blood withdrawals is defined as following:
- max. number of blood withdrawals in case of therapy process: 4
- max. number of blood withdrawals for multiple blood withdrawals (latent infection/non-infected subjects): 5

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Organizational Data

  •   DRKS00012556
  •   2017/11/17
  •   [---]*
  •   no
  •   Approved
  •   17-571-122, Ethikkommission an der Universität Regensburg
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Secondary IDs

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Health Condition or Problem studied

  •   diagnosis, differentiation of patients/subjects with active or latent tuberculosis infection and non-infected patients/subjects
  •   A15 -  Respiratory tuberculosis, bacteriologically and histologically confirmed
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Interventions/Observational Groups

  •   Patients with active TB disease (clinically confirmed): 330-440
    study specific measurements: RTT-Verfahren, IGRA-test, questionnaire


  •   Patients/ Subjects with latent TB infection (340-400)
    - Inclusion of patients with positive Interferon-Gamma-Release-Assay (IGRA) (e.g. detected during screening prior to the start of immunosuppressive therapy in case of Rheumatoid arthritis)
    - Inclusion of subjects identified to be latently infected in „contact screenings“
    - Healthcare workers with known latent TB infection
    - Subjects following successful termination of treatment of an active TB disease 2 months to 20 years ago
    study specific measurements: RTT-Verfahren, IGRA-test, questionnaire
  •   Non-infected patients/subjects (275-400)
    - Inclusion of subjects without any known (current or former) contact to persons with suspected active TB disease
    - Inclusion of patients with negative Interferon-Gamma-Release-Assay (IGRA) (detected during screening prior to the start of immunosuppressive therapy for instance in case of Rheumatoid arthritis)
    study specific measurements: RTT-Verfahren, IGRA-test, questionnaire
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Diagnostic
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Optimization of RTT method (in terms of practicability and robustness i.e. minimizing the impact of external influences and maximizing user-friendliness) by analyzing the following parameters or procedure steps, respectively:
- Sample quality
- Stimulation
- Component testing
- Read-out

For individual questions:
- Optimization: Signal increase by a factor of at least 1.5
- Consistency: Signal variation by a factor of less than 1.5

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Secondary Outcome

Investigation of potential influencing factors such as Rifampicin-therapy (=“TB treatment“) or immunosuppressive therapy (only patients intended for therapy due to an underlying disease such as Rheumatoid Arthritis).
For these analyses, a small cohort (of at least 15 patients per experiment) will be included for “tracking of therapy process”.
Only valid from version 06.00: In addition to the above defined group of patients with follow-up during treatment, a defined cohort of 50-60 patients already treated when arriving at the study site will be allowed to be included into the study. Treatment may not exceed seven days. The treated group will be analysed in a joint and separate evaluation from the untreated group to investigate possible differences:

- No influence by treatment: Consistent signal (variation by a factor of less than 1.5) with and without treatment or comparable sensitivities in Rif-treated vs. Rif-untreated patients, respectively
- Influence by treatment: Signal decrease or increase of at least 1.5 or distinct sensitivities in Rif-treated vs. Rif-untreated patients, respectively

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Countries of Recruitment

  •   Germany
  •   Austria
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2017/09/25
  •   1240
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- At least 18 years of age
- Known TB infection status (i.e. active disease, latent infection or non-infected with M. tuberculosis) or TB infection status is planned to be determined during study duration
- Given blood donation compatibility
- Written informed consent

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Exclusion Criteria

- Known to be positive for HIV or chronic hepatitis infection
- Presence of any form of substance abuse, psychiatric disorder or condition that in the opinion of the investigator may impair the communication with the investigator or the patient’s compliance
- More than 7 days of treatment with any antituberculous drug in patients with suspect for active TB disease
- If not intended for tracking of therapeutic process:
o patients under Rifampicin treatment within the last 2 months : exception (valid from version 06.00): a defined cohort of patients who have started Rifampicin treatment (<7d) prior to referral to study site may be included (communication and confirmation by the sponsor is mandatory)
o patients under immunosuppressive therapy (biologics or >10mg steroids) within the last 2 months
- If intended for tracking of therapeutic process:
o Patients with TB infection under Rifampicin treatment already started prior to the planned visit 1
o Latent and non-infected patients under immunosuppressive therapy (biologics or >10mg steroid) already started prior to the planned visit 1
- in Austria only: pregnancy

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Addresses

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    • Lophius Biosciences GmbH
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Lophius Biosciences GmbH
    • Ms.  Dr.  Alexandra  Asbach-Nitzsche 
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Lophius Biosciences GmbH
    • Ms.  Dr.  Traudel  Schmidt 
    • AmBiopark 13
    • 93053  Regensburg
    • Germany
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Sources of Monetary or Material Support

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    • Lophius Biosciences GmbH
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Friedrichstraße 130 B
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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