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

• Register: EUCTR
• Last refreshed on: 26 April 2021
• Main ID: EUCTR2016-003360-39-DE
• Date of registration: 11/04/2017
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinikum Freiburg
• Public title: Safety and efficacy of Abatacept in patients with treatment-resistant sarcoidosis
• Scientific title: Safety and efficacy of Abatacept in patients with treatment-resistant sarcoidosis - ABASARC
• Date of first enrolment: 27/06/2017
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003360-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Leiter der Klinischen Prüfung
• Affiliation: Universitätsklinikum Freiburg

• Name: Leiter der Klinischen Prüfung
• Affiliation: Universitätsklinikum Freiburg

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent
2. Ability to understand the nature, significance and consequences of the study and to comply with them
3. Age 18 years or above; male or female patients
4. Diagnosis of sarcoidosis according to the current applicable ATS/WASOG guidelines
5. Immunosuppressive therapy (= 5 mg prednisolone equivalent per day or any additional immunosuppressive therapy independently of the steroid dose) within the last 3 months prior screening for pulmonary involvement as defined by one of the following
a. Radiographic alterations in HRCT compatible with sarcoidosis
b. Lung function impairment caused by sarcoidosis (e.g. reduced TLC, FVC, reduced DLCO, reduced pO2 at rest or exercise-induced)
6. King’s Sarcoidosis Questionnaire (KSQ), GHS L module: Score < 80
7. Need for therapy escalation beyond 5 mg prednisolone equivalent according to the physician’s appraisal, e.g.:
a. Disease activity only controlled by > 5 mg prednisolone equivalent
b. Disease progression under established immunosuppressive therapy according to clinician’s appraisal (e.g. lung function deterioration, CT-graphic progression, increase of activity parameters)
c. Need for change of immunosuppressive therapy because of therapy-associated side effects
8. Elevated sIL2 receptor levels and/or elevated Neopterin as sign of T-cell activation within 6 months prior to date of informed consent
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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), for example but not limited to active hepatitis B and C, typical or atypical mycobacteriosis or herpes zoster infections.
9. History of or active psychiatric disease (including known history of or current active abuse of drugs, chemicals or alcohol) 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. Examples are cardiovascular (e.g. severe uncontrolled hypertension, instable angina pectoris, severe ischemic heart disease), central nervous system (e.g. stroke, dementia), hepatic, renal, endocrine (e.g. uncontrolled diabetes), gastrointestinal (e.g. complicated diverticulitis, Crohn’s disease, colitis ulcerosa)
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Steroid-refractory Sarcoidosis
MedDRA version: 20.0 Level: PT Classification code 10037430 Term: Pulmonary sarcoidosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: ORENCIA
Pharmaceutical Form: Solution for injection in pre-filled syringe

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 months after first application of study medication

Main Objective: To assess the safety of Abatacept in patients with treatment-resistant sarcoidosis, measured as number of infectious complications during treatment period

Primary end point(s): 1. Number and characterization of severe infectious complications during Abatacept treatment period, defined as:
a. Opportunistic infections
b. Infections requiring hospitalization
c. Infectious requiring intravenous antibiotic treatment (including anti-fungal or anti-viral drugs)
d. EBV reactivation

Secondary Objective: To assess the efficacy of Abatacept in patients with treatment-resistant sarcoidosis

Secondary Outcome(s)

Secondary end point(s): 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. Patients’ reported outcome as Patients
a. change in Kings Sarcoidosis Questionnaire (KSQ) > 6
b. St. George Respiratory Questionnaire (SGRQ)
c. Leicester Cough Score (LCS)
4. Pulmonary function test
a. TLC
b. FVC
c. DLCOcSB
d. DLCOc/VA
e. pO2 at rest and after 6MWT
f. DSP (distance walked * SaO2/100)
g. AaDO2
5. Laboratory parameters
a. sIL2R
b. Neopterin
c. ACE
d. IL17
e. Total white blood cell count
i. B- and T-cell count
ii. Characterization of B- and T-cell types
f. mRNA measurement (blood)
6. Bronchoalveolar lavage parameters
a. Total cell count /100ml lavage fluid
b. Percentage of differential cell count
c. Subtypes of T-cells in bronchoalveolar lavage
d. Cytokines in cell culture supernatant from bronchoalveolar cells (e.g. TNF, MIP-1a, IL-12p40, CXCL10 (IP-10), IL10, TGFß, IFNgamma IL13, IL8 and IL17)
e. mRNA measurement
7. Need for therapy escalation
a. Daily steroid dose
b. Need for steroid pulses
c. Need for therapy modification

Timepoint(s) of evaluation of this end point: For more details, please refer to chapter 13.5.2 of the protocol.

Secondary ID(s)

BMS_IM101-631

Deutsches Register Klinischer Studien

Source(s) of Monetary Support

Bristol-Myers Squibb GmbH & Co. KGaA

Ethics review

Status: Approved
Approval date: 27/06/2017
Contact: