EBIO - Enthesitis Biopsy Study

• Status: Recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this Phase IV study is to determine the effect of secukinumab on total immune cell numbers obtaines by entheseal biopsy in the inflamed human entheses in patients with Psoriatic Arthritis. This is a single arm, single centre, prospective, open label study with secukinumab.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Erlangen-Nürnberg Medical School

Criteria

The trial population consists of patients of both sexes, aged ≥ 18 years, with active psoriatic arthritis and an indication for systemic treatment.

Patient eligible for study participation will have to fulfil the following requirements:

• Must be male or female and aged > 18 years at time of consent

• Clinical signs of enthesitis for at least 6 weeks prior to enrolment

• Indication for systemic treatment for PsA according to guidelines

• Patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine or methotrexate

• bDMARD and tsDMARD naive

• Must understand and voluntarily sign an informed consent form including written consent for data protection

• Must be able to adhere to the study visit schedule and other protocol requirements

• Male subjects (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with Females of Childbearing Potential (FCBP) while on study medication and for at least 28 days after taking the last dose of study medication.

• Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening and must be willing to use one effective form of birth control when engaging in reproductive sexual activity while on study medication and for at least 28 days after taking the last dose of study medication.

Effective contraception methods include:

1. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception;

2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy);

3. total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;

4. Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner of that Patient;

5. Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps)

6. Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1 percent), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS); In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking investigational drug; In case local regulations deviate from the methods listed, local regulations apply and will be described in the ICF; Women are considered post-menopausal and not of child bearing potential if they have had at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago.

Additional eligibility criterium prior to enthesial biopsy:

• Presence of inflammation (enthesitis, synovitis, tendinitis, osteitis or tenosynovitis) in MRI or ultrasound examination of the elbow/ankle must be detectable

Exclusion criteria:

• Any contraindications for the treatment with secukinumab

• Subjects requiring systemic anticoagulation therapy or suffering from coagulation disorders or any other condition which might interfere with enthesitis tissue sampling

• IBD (e.g. Crohn´s disease, ulcerative colitis)

• Investigational study drug within 4 weeks (or 5 half-lives, whichever is longer) prior to enrolment

• Patients taking high-potency opioid analgesics, including but not limited to, methadone, hydromorphone, and morphine

• Any contraindication or unwillingness to perform MRI

• Rheumatologic, inflammatory diseases, including but not limited to: AS, RA

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception

• Any underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, psychiatric, endocrine, cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator immune-compromises the patient and/or places the patient at unacceptable risk for participation in a secukinumab therapy

• Active systemic infections during the last two weeks (exception: common cold) prior to enrolment.

• Evidence of tuberculosis infection as defined by either a positive purified protein derivative (PPD) skin test (the size of induration will be measured after 48-72 hours, and a positive result is defined as an induration of ≥ 5mm or according to local practice/guidelines), or a positive Quantiferon test. Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must have been initiated prior to enrolment.

• Infection with human immunodeficiency virus (HIV) Hepatitis B (HBV) or Hepatitis C (HCV)

• History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed), treated or untreated within the past 5 years prior to enrolment.

• History or evidence of ongoing alcohol or drug abuse, within the last six months prior to enrolment.

• Planned administration of live vaccines during the study period or within 6 weeks prior to enrolment.

• Patients who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g. family members).