Trial document




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  DRKS00011660

Trial Description

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Title

Safety and efficacy of Abatacept in patients with treatment-resistant sarcoidosis

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Trial Acronym

ABASARC

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URL of the Trial

[---]*

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Brief Summary in Lay Language

The main objective of this study is to assess the safety and efficacy of a drug called Abatacept in patients with sarcoidosis. Sarcoidosis is a condition that mainly affects the lungs, but other organs of the body as well. Sarcoidosis is caused by an exaggerated immune response to a yet not identified antigen. The immune response may affect different organs (especially the intrathoracic lymph nodes as well as the lung) leading to functional deterioration. While roughly two thirds of sarcoidosis patients undergo spontaneous recovery of the disease some patients do experience chronic illness leading to reduced quality of life and functional organ impairment requiring immunosuppressive therapy (e.g. steroids). In case of insufficient response and steroid caused side reactions other disease-modifying drugs (second line therapy) may be needed to down-regulate immune system. High quality studies for these disease-modifying drugs used in sarcoidosis patients are missing resulting in a lacking approval of any drug for treating sarcoidosis in Germany.
Based on the observation of an exaggerated immune response in sarcoidosis and the pathophysiological processes leading to sarcoidosis a drug called Abatacept (marketed as ORENICA ®) might dampen the immune response and exert a positive influence on sarcoidosis. For this drug, similar results have already been obtained for other diseases that are characterized by an exaggerated immune response

Abatacept is a protein that inhibits the co-operation of different cells of the immune system, thus regulating the inflammation and bringing down the reaction of the immune system against the body's own tissues. This medicine has been successfully used to treat patients with an inflammation of the joints (rheumatoid arthritis).

In the present study, 30 patients with sarcoidosis shall be treated with Abatacept for a period of 12 months, by way of a self-administered subcutaneous injection once weekly. The safety and efficacy of Abatacept are measured as rate and type of infectious complications, as well as assessment of pulmonary function, blood samples, and quality-of-life surveys. The hypothesis of this study is that Abatacept is safe and effective in treating patients with sarcoidosis.

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Brief Summary in Scientific Language

This is a multicenter, prospective, single arm phase II trial.

The primary objective is to assess the safety of Abatacept in patients with treatment-resistant sarcoidosis, measured as number of severe infectious complications during treatment.
The secondary objective is to assess further safety endpoints in terms of (serious) adverse events as well as efficacy endpoints such as sarcoidosis-specific patient-reported outcomes, pulmonary function, laboratory parameters (blood and BAL) and need for therapy escalation.

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Organizational Data

  •   DRKS00011660
  •   2017/10/05
  •   [---]*
  •   yes
  •   Approved
  •   163/17(FF-MC), Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   2016-003360-39 
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Health Condition or Problem studied

  •   D86.0 -  Sarcoidosis of lung
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Interventions/Observational Groups

  •   Abatacept (ORENCIA®) 125 mg s.c. once weekly for 12 months, self-administered injection
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Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   Yes
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Primary Outcome

1. Number and characterization of severe infectious complications during Abatacept treatment period

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Secondary Outcome

1. Rate of infectious complications during Abatacept treatment period compared to infectious complications within a 1 year prior to first application of trial medication

2. Rate of adverse events and serious adverse events

3. Change in Patients’ reported outcome (King’s Sarcoidosis Questionnaire, Leicester Cough Questionnaire and St. George’s Respiratory Questionnaire, each assessed at screening, week 24, week 52)

4. Pulmonary function, assessed at screening and at week 12, 24, 36, 48, 52

5. Laboratory parameters, in part I of the study* assessed at screening and at week 6, 12, 18, 24, 30, 36, 42, 48, 52. In part II of the study*, assessment at week 6, 18, 30, 42 might be omitted, depending on the decision of the Data Monitoring Committee.

6. Bronchoalveolar lavage parameters, assessed at screening and at week 52

7. Need for therapy escalation



* The trial consists of two parts. In both parts, regular visits are scheduled at screening and at week 12, 24, 36, 48, 52. In part I, the first 6 patients are included in the study for whom additional safety visits are scheduled at week 6, 18, 30, 42. A Data Monitoring Committee then decides if these additional visits are necessary in part II, i.e. for the remaining 24 patients, or if the regular visits are sufficient.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/02/21
  •   30
  •   Multicenter trial
  •   National
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Inclusion Criteria

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

1. Signed written informed consent
2. Diagnosis of sarcoidosis according to current applicable ATS/WASOG guidelines
3. Immunosuppressive therapy (>5mg prednisolone equivalent per day or additional immunsuppressive therapy) within the last 3 months prior screening
4. Kings Sarcoidosis Questionnaire (KSQ): Score < 80
5. Need for therapy escalation beyond 5 mg prednisolone equivalent according to the physician’s appraisal
6. Elevated sIL2 receptor levels and /or elevated Neopterin as sign of T-cell activation within 6 months prior to date of informed consent

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Exclusion Criteria

1. Severe lung functional impairment according to the treating physician interfering substantially with participation in the trial
2. End stage fibrotic lung disease without expected improvement to immunosuppressive therapy as judged by the treating physician
3. Concomitant lung disease (e.g. COPD, asthma) that interferes with clinical assessment as judged by the treating physician
4. Concurrent immunosuppressive therapy other than corticosteroids and impossibility to allow a sufficient wash-out phase
5. For biologicals a wash-out phase of two months is mandatory
6. Previous treatment with Abatacept
7. Treatment with another investigational drug within 4 weeks or 5 half-lives prior to first application of trial medication
8. Recurrent or active current bacterial, viral or fungal infection (excluding fungal infections of the nails)
9. History of or active psychiatric disease interfering with the safe participation in the study
10. History of or current primary or secondary immunodeficiency that could not be attributable to treatment-related immunodeficiency
11. Serious uncontrolled concomitant diseases not caused by sarcoidosis
12. Known malignancy or high clinical suspicion on malignant disease
13. Lymphoma within the last five years
14. Contraindications against treatment with Abatacept
15. Simultaneous application of live vaccines
16. Simultaneous participation in other interventional clinical trials
17. Pregnancy indicated by positive urine pregnancy test
18. Breast-feeding patients
19. Fertile patients refusing to use safe contraceptive methods during the study

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Addresses

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    • Universitätsklinikum Freiburg
    • Breisacher Str. 153
    • 79110  Freiburg
    • Germany
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    • Universitätsklinikum FreiburgKlinik für Pneumologie
    • Mr.  Prof. Dr. med.  Joachim  Müller-Quernheim 
    • Killianstr. 5
    • 79106  Freiburg
    • Germany
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    • Universitätsklinikum FreiburgKlinik für Pneumologie
    • Mr.  Prof. Dr. med.  Joachim  Müller-Quernheim 
    • Killianstr. 5
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Bristol-Myers Squibb GmbH & Co. KGaA
    • Arnulfstraße 29
    • 80636  München
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.