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Tofacitinib: salvage therapy for patients with RCDII - a pilot study

Phase 2
Recruiting
Conditions
gluten intolerance
refractory celiac disease type II
10025321
10017969
Registration Number
NL-OMON52502
Lead Sponsor
Vrije Universiteit Medisch Centrum
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
Not specified
Target Recruitment
4
Inclusion Criteria

1. Adult patients >= 18 years old
2. Given informed consent
3. Diagnosis of RCDII
4. Total adherence to a gluten-free diet (GFD) for at least 6 consecutive
months prior to screening. Subjects must also agree to make no changes to their
current GFD for the duration of study participation.
5. Anti-tissue transglutaminase (IgA and IgG at screening < 2x the diagnostic
level for celiac disease (weak positive or negative).
6. In case of female fertile patients: adequate contraception, up to 4 weeks
after final dose.
7. Laboratory values:
a) Total WBC > 0.75 x 109/L (i.e. > 750/mm3)
b) Hemoglobin > 5.5 mmol/L (i.e. 8.86 g/dL)
c) Absolute neutrophil count > 1 x 109 / L (i.e. > 1000 cells/mm3.)
d) Estimated eGFR > 30mL/min/1.73m2 using the Cockcroft-Gault equation.
e) Platelets > 50 x 109/L (i.e. 50000/mm3)
8. PET/CT-scan without signs of abnormalities suggestive for EATL within 3
months.
9. Willingness and ability to comply with study procedures.
10. Willingness to return for all scheduled follow-up visits.

Exclusion Criteria

1. Diagnosis of RCDI, EATL
2. Presence of any of the following diagnosis:
a) Severe infection prior to screening (e.g. those requiring hospitalization of
parenteral antimicrobial therapy or opportunistic infections. Specific
attention for treatment with ketoconazol or fluconazole (as well CYP3A4
metabolizers)).
b) Active tuberculosis (TBC)
c) Untreated or inadequately treated latent TBC
d) History within 3 years of opportunistic infections typical of those seen in
immunocomprised patients, such as systemic candida infection; disseminated
herpes zoster.
e) Severe liver insufficiency (Child Pugh Score 10-15).
3. Positive Hep B or Hep C test results at the time of screening.
4. Vaccination with live, attenuated vaccines (such as varicella zoster
vaccine, yellow fever or oral typhoid vaccine) within 2 weeks before start of
tofacitinib.
5. History of significant immune suppression:
a) BMT therapy less than 6 months prior to baseline
b) Potent systemic immune suppressants (e.g., azathioprine, within specified
time periods per immunosuppressant) prior to baseline.
6. Subjects receiving moderate/potent CYP3A inducers or inhibitors in the
specified time periods prior to the first dose of study drug.
7. Screening 12-lead ECG that demonstrates clinically relevant abnormalities
which may affect subject safety or interpretation of study results.
8. History or presence of clinically significant disease that in the opinion of
the investigator would confound the subject*s participation and follow-up in
the clinical trial or put the subject at unnecessary risk (e.g. uncontrolled
cardiac diseases, uncontrolled/chronic pulmonary, renal, endocrine,
hematological, gastrointestinal, immunologic, dermatological, neurological or
psychiatric dysfunction).
i. Specific attention for risk factors for pulmonary embolism, such as:
use of hormonal contraception, heart failure, previous venous thromboembolism,
hereditary coagulation disorder, malignancy, patients who get major surgery.
9. History of drug or alcohol abuse that would interfere with the ability to
comply with the study protocol.
10. History of clinically significant hypersensitivity to the study drug or to
any of the excipients
11. Females who are pregnant, becoming pregnant or are currently breastfeeding.
12. Participation in any other investigational drug study in the past 30 days/5
half-lives.
13. Any additional reason which would endanger safety of the subject for
participation in this study, in the opinion of the investigator.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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