JAK INHIBITION IN PRECLINICAL ARTHRITIS

Phase 2

Recruiting

Conditions: M05
Seropositive rheumatoid arthritis

Registration Number: DRKS00032648

Lead Sponsor: niversitätsklinikum Erlangen, Medizinische Klinik3, Rheumatologie und Immunologie

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 20

Inclusion Criteria

Must read and understand the informed consent approved by the institutional review board (IRB)/ethics review board (ERB) governing the site and provide written informed consent.
• Female and male patients are at least 18 and at most 64 years of age
• Non-pregnant, non-breastfeeding female patient
a. Female patients of child-bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with the opposite sex.
b. Total abstinence is defined as refraining from intercourse during the entirety of the study and for at least 1 week following the last dose of investigational product. Periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception.
c. Otherwise, female patients of childbearing potential must agree to use 2 effective methods of contraception, where at least 1 form is highly effective, for the entirety of the study and for at least 1 week following the last dose of investigational product.
d. The following contraception methods are considered acceptable (the patient should choose 2, and 1 must be highly effective [defined as less than 1% failure rate per year when used consistently and correctly]):
• Highly effective birth control methods:
o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
o Progestogen- only containing hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
o intrauterine device (IUD)/intrauterine hormone-releasing system (IUS)
o vasectomized male (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
• Effective birth control methods:
o Male or female condom with spermicide. It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these methods are combined.
• Diaphragm with spermicide
• Cervical sponge
• Cervical cap with spermicide
• Note: When local guidelines concerning highly effective or effective methods of birth control differ from the above, the local guidelines must be followed.
e. Female patients of non-child-bearing potential are not required to use birth control and they are defined as:
• Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation)
• Post-menopausal – defined either as
o A woman at least 50 years of age with an intact uterus, not on hormone therapy, who has either
o Cessation of menses for at least 1 year
o At least 6 months of spontaneous menorrhea with follicle-stimulating hormone >40 mIU/mL
o Women aged 55 years or older who are not on hormone therapy, and who have had at least 6 months of spontaneous amenorrhea
o Women aged 55 years or older who have a diagnosis of menopause
• Clinical: no arthritis in 76/78 joint count
• Imaging: = 1 B-Mode or PD (Power Doppler) signal with ultrasound at one of the 76/78 joints or flexor/extensor tendons of hand or feet
• Autoantibodies: (2 different Autoantibodies are compulsory, one of them anti-CCP antibodies)
o Anti-CCP antibody positivity at Screening
o Anti-modified antibodies: citrullinated vi

Exclusion Criteria

Patients will be excluded from study enrollment if they meet any of the following criteria:
• Clinically apparent arthritis (76/78 joint count)
• Fulfilment of ACR/EULAR 2010 Classification Criteria for RA
• Any previous therapy with bDMARD/tsDMARD/cDMARD
• Ongoing pregnancy status or breast-feeding
• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months or according to local guidelines, prior to screening and evaluated by a qualified physician
• Contraindication for Baricitinib treatment according to its SmPC
• Any malignancy risk factor (e.g. current malignancy or history of malignancy)
The following may be exempted:
a) Patients with cervical carcinoma in situ that has been resected with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study.
b) Patients with basal cell or squamous epithelial skin cancers that have been completely resected with no evidence of recurrence for at least 3 years may participate in the study.
• Any pre-existing condition that constitutes a risk factor for major adverse cardiovascular events (e.g. history of stroke, coronary heart disease, myocardial infarction, current or past long-time smoker)
• Any known VTE risk factor (e.g. previous DVT/PE or inherited coagulation disorder)
• Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the patient.
• Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study.
• Have a history of diverticulitis.
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
• Have a history of lymphoproliferative disease; have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly.
• Have a current or recent (< 4 weeks prior to randomization) clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection that in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
Note: For example, a recent viral upper respiratory tract infection or uncomplicated urinary tract infection need not be considered clinically serious.
• Have symptomatic herpes simplex at the time of randomization.
• Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
• Have a history of disseminated/ complicated herpes zoster (for example, ophthalmic zoster or CNS involvement).
• Have a positive test for hepatitis B virus (HBV) defined as:
a) positive for hepatitis B surface antigen (HBsAg), or
b) positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)
Note: Patients who are HBcAb-positive and HBV DNA-negative may be enrolled in the study but will require additional HBV DNA monitoring during the study.
• Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribon

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
umber of patients with development of arthritis at week 48

Secondary Outcome Measures

Name	Time	Method
-number of patients with development of arthritis at week 24<br>-Fulfillment of the ACR/EULAR 2010 RA classification criteria<br>-Ultrasound: number of patients without signs of PD synovitis or PD tenosynovitis at week 24 and week 48 compared to baseline and compared within both groups<br>-Change in anti CCP2 antibody levels (RE/ml)<br>-Change in anti CCP2 antibody levels (RE/ml) in HLA-defined subgroups<br>-Glycosylation profile of total IgG and CCP2 antibodies<br>-Number and frequency of total and CCP2-specific B cells<br>-MS-based unbiased metabolic profiling of plasma metabolites<br>-Changes in GBP1 levels<br>-Patients without tender joints at week 48 compared to baseline<br>-TJC/SJC 76/78, HAQ, DAS28-CRP, SDAI/CDAI<br>-Patient VAS global, VAS pain; VAS physician<br>-Subjective (SACRAH, sMHQ) and objective (moberg pick up test (MPUT)) hand function