Psoriatic arthritis MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859
Conditions
Interventions
Trade Name: Cosentyx
Product Name: Cosentyx
Product Code: EU/1/14/980/002
EU/1/14/980/003
Pharmaceutical Form: Solution and suspension for suspension for injection in pre-filled syringe
INN or Proposed INN: Secukinumab
CAS Number: 1229022-83-6
Other descriptive name: SECUKI
EU/1/14/980/005
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Secukinumab
CAS Number: 1229022-83-6
Other descriptive name: SECUKINUMAB
Concentration unit: mg milli
Sponsors
Universitätsklinikum Erlangen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. • Inadequate response or intolerance or contraindications to other systemic therapy incl. cyclosporine or methotrexate • bDMARD and tsDMARD naive • 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 baseline and must be willing to use one highly-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. • 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 Additional eligibility criterium Prior to enthesial biopsy: • Signs of inflammation (enthesitis, synovitis, tenosynovitis, tendinitis or osteitis) in MRI or ultrasound examination of the elbow/ankle 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Any contraindications for the treatment with secukinumab • Any contraindication or unwillingness to perform MRI • Subjects requiring systemic anticoagulation therapy or suffering from coagulation disorders or any other condition which might interfere with enthesitis tissue sampling • Rheumatologic, inflammatory diseases, including but not limited to RA, AS • IBD (e.g. Crohn´s disease, ulcerative colitis) • Any other underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, psychiatric, endocrine, cardiac, infectious, gastrointestinale, or other condition which in the opinion of the investigator places the subject at an unacceptable risk for participation in a secukinumab therapy • Active systemic infections during the last two weeks (exception: common cold) • Evidence of tuberculosis as defined by either a positive PPD skin test 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 HIV, HBV or HCV • Subjects taking high-potency opioid analgesics, including but not limited to methadone, hydromorphone, and morphine • History of lymphoproliferative disease or malignancy of any organ system (except for basal cell carcinoma or actinic keratosis 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) within the past 5 years prior to enrolment • Planned administration of live vaccines during the trial period or administration within 6 weeks prior to enrolment • Pregnant (confirmed by a positive human chorionic gonadotropin (hCG) laboratory test) or nursing women • Women of childbearing potential, unless they are using effective methods of contraception • History or evidence of ongoing alcohol or drug abuse within the last six months prior to enrolment • Participation in an IMP or IMD trial within 4 weeks (or, for IMPs, 5 half-lives, whichever is longer) prior to screening visit • Patients who possibly are dependent on the sponsor, the principal investigator or investigator (e.g. family members
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Defining the effect of IL-17A inhibition on total immune cell numbers (PMN, M?, T cells, B cells, ILC3, Mast cells) in inflamed human entheses.;Secondary Objective: Defining the effect of IL-17A inhibition on • the number of IL-17 expressing cells in the inflamed human entheses • the expression of IL-17 pathway and bone formation genes in the inflamed human entheses • enthesial inflammation in imaging • clinical signs of enthesitis, arthritis, skin disease, physical function and quality of life ;Primary end point(s): Percent of patients with reduction of total immune cell numbers (PMN, M?, T cells, B cells, ILC3, Mast cells) by at least 50% in the enthesial tissue ;Timepoint(s) of evaluation of this end point: after 24 weeks of Treatment with secukinumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in numbers of MPO+ neutrophils and CD11b+ macrophages in enthesial biopsies • Change in numbers of CD3+ T cells and CD20+ B cells in enthesial biopsies • Change in numbers of ILC3 (CD4-, IL-7R+, c-Kit+) and tryptase+ mast cells in enthesial biopsies • Change in numbers and types of IL-17+ cells in enthesial biopsies • Gene expression related to the IL-23/IL-17 pathway (IL-17A, IL-17F, IL-23, IL-22, TNFalpha, COX2, IL-8) in enthesial biopsies • Gene expression related to bone formation molecules (IHH, BMP2, Wnt3a, Wnt5a, Runx2, OCN) in enthesial biopsies • Extent of enthesitis and osteitis in MRI (elbow/ankle) • Extent of enthesitis in ultrasound examination (elbow/ankle) • Change in clinical enthesitis (SPARCC) • Change in clinical arthritis (SJC, TJC, DAPSA) • Change in clinical skin disease (PASI) • Number of subjects with minimal disease activity (MDA) • Pain (VAS), physical function (HAQ-DI) and impact of disease (PSAID) ;Timepoint(s) of evaluation of this end point: Screening/Baseline compared to week 24 | — |
Countries
Germany
Contacts
Public ContactMedizinische Klinik 3
Universitätsklinikum Erlangen
Outcome results
None listed