Phase IIb in Rheumatoid Arthritis

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2017-000384-32-CZ
• Lead Sponsor: Merck KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-26
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 363

Inclusion Criteria

The current trial will enroll subjects who fulfill the following key inclusion criteria:
• Consenting male or female subjects, 18 to 75 years of age
• Confirmed diagnosis of RA according to 2010 ACR/EULAR RA classification criteria of at least 6 months duration prior to Screening
• Persistently active moderate to severe RA at both Screening and Randomization (if significant surgical treatment of a joint has been performed, that joint cannot be counted for entry or enrollment purposes), as defined by:
o = 6 swollen joints (of 66 assessed) and
o = 6 tender joints (of 68 assessed).
• An hsCRP = 5.0 mg/L (= 0.50 mg/dL) at Screening
• Treatment for = 16 weeks with 7.5 to 25 mg/week MTX at a stable dose and route of administration (oral or parenteral) for at least 8 weeks prior to dosing with the IMP and maintained throughout the trial
• For subjects entering the trial on MTX doses < 15 mg/week, there must be clear documentation in the medical record that higher doses of MTX were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines.
MRI Substudy Subjects:
In addition to meeting the inclusion criteria for the study, subjects must
have palpable synovitis of the wrist and/or = 1 of MCP joints #1 to #5,
defined as loss of bony contours with palpable joint effusion and/or
swelling, in the MRI-designated hand (i.e., the hand being used in MRI
assessments).
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 308
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

Exclusion Criteria

Subjects who fulfill any of the following key exclusion criteria should not be enrolled into this trial:
• ACR functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound
• Use of oral corticosteroids > 10 mg daily prednisone equivalent, or change in dose of corticosteroids within 2 weeks prior to Screening or during Screening
• Use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid within 4 weeks prior to Screening or during Screening
• Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) (including low-dose aspirin and COX-2 inhibitors) within 2 weeks prior to dosing with the IMP
• High potency opioid analgesics are prohibited within 2 weeks prior to
Screening and during the trial; other analgesics are allowed (e.g.,
acetaminophen, codeine, hydrocodone, propoxyphene, or tramadol),
although not within 24 hours of study visits with clinical assessments
(not approved in Japan).
• Current or prior treatment with ANY of the following:
o Biologic DMARDs (approved or investigational), including but not limited to:
-TNF antagonists or biosimilars of these agents (approved or investigational), or any investigational TNF antagonist
- Interleukin-6 antagonists
- Abatacept (CTLA4-Fc)
- Anakinra (IL-1 receptor antagonist)
- B cell-depleting antibodies (e.g., rituximab, ocrelizumab, ofatumumab, obinutuzumab, ocaratuzumab, veltuzumab, or any biosimilars of these agents [approved or investigational])
- Anti-BLyS (B lymphocyte stimulator) agents (e.g., belimumab, tabalumab)
- Dual BLyS/A proliferation-inducing ligand (APRIL) neutralizing agents (e.g., atacicept, RCT-18).
o Targeted synthetic DMARDs (approved or investigational), specifically:
- Janus kinase inhibitors
- Other Bruton’s tyrosine kinase (BTK) inhibitors
o Alkylating agents (e.g., chlorambucil, cyclophosphamide).
• The following restrictions on non-biologic DMARD must be followed, otherwise the subject is excluded:
o Auranofin (Ridaura®), minocycline, penicillamine, sulfasalazine, cyclosporine, mycophenolate, tacrolimus, azathioprine: must have been discontinued for 4 weeks prior to dosing with the IMP
o Leflunomide (Arava®) must have been discontinued 12 weeks prior to dosing with the IMP if no elimination procedure is followed. Alternately, it should have been discontinued with the following elimination procedure at least 4 weeks prior to dosing with the IMP: Cholestyramine at a dosage of 8 g 3 times a day for at least 24 hours, or activated charcoal at a dosage of 50 g 4 times a day for at least 24 hours.
o Injectable Gold (aurothiglucose or aurothiomalate): must have been discontinued for 8 weeks prior to dosing with the IMP
o Anti-malarials (hydroxychloroquine, chloroquine) will be allowed in this trial. Subjects may be taking oral hydroxychloroquine (= 400 mg/day) or chloroquine (= 250 mg/day), doses must have been stable for at least 12 weeks prior to dosing with the IMP, and will need to be

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified