A Study to Evaluate the Safety and Efficacy of RO7123520 as Adjunct Treatment in Patients With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to TNF-a Inhibitors

• Register: EUCTR
• Last refreshed on: 10 December 2018
• Main ID: EUCTR2016-002126-36-AT
• Date of registration: 11/11/2016
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study to Evaluate the Safety and Efficacy of RO7123520 as Adjunct Treatment in Patients With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to TNF-a Inhibitors
• Scientific title: A randomized, double-blind, placebo-controlled, multi-center, three-part phase II study to evaluate the safety and efficacy of RO7123520 as adjunct treatment in patients with moderately to severely active rheumatoid arthritis and an inadequate response to TNF-a inhibitors
• Date of first enrolment: 01/03/2017
• Target sample size: 204
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002126-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Chile, Colombia, Czech Republic, Germany, Guatemala, Italy, Mexico, Peru, Poland, Spain, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Adult men and women, of more than 18 to 80 years of age (inclusive)
- Diagnosis of adult-onset RA as defined by the American College of Rheumatology (ACR) 2010 criteria, for at least 6 months before screening
- Moderately to severely active RA as defined by at least 4/28 tender joints and at least 4/28 swollen joints
- For Part 2 only: Active synovitis and/or osteitis of the hand/wrist as determined by MRI
- Patients must be taking one of the following anti-TNF-a therapies: certolizumab, golimumab, etanercept, adalimumab, infliximab or approved biosimilars of these, given at a recommended approved and stable dose for at least 12 weeks before randomization, and have experienced in the opinion of the Investigator an inadequate response to anti-TNF-a therapy with a DAS28 => 3.2
- Patients must be taking MTX (PO, SC, or IM) for at least 12 weeks before randomization and must be on a stable dose for at least 4 weeks before randomization (5.0 to 25 mg/week). The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons. Local standard-of-care should be followed for concomitant administration of folic acid
- Patients on glucocorticoids (<= 10 mg/day PO prednisone or equivalent) are permitted if doses are stable within 6 weeks of planned randomization
- Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (e.g., up to 2-3 times weekly) for short-term relief of pain are allowed, and patients on regular NSAID use (i.e., on stable dose for = 4 weeks) are allowed
- Negative pregnancy test at screening and baseline (women only), and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation
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 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
- Previous, current or planned non-TNF-a therapy treatment for RA, such as tocilizumab, anakinra, abatacept or rituximab, etc.
- Currently receiving concomitant treatment with hydroxychloroquine, sulfasalazine, or leflunomide
- Patients currently on IV infliximab or an approved IV biosimilar of it are excluded
- Parenteral glucocorticoids administration (IM, IV) of =50 mg within 6 weeks prior to planned randomization, or =50 mg within 4 weeks prior to planned randomization, or scheduled parenteral administrations during the study
- Joints injected with intra-articular glucocorticoids or hyaluronic acid within 6 weeks prior to planned randomization
- Active inflammatory disease of the joints not related to RA or other systemic autoimmune disease
- Systemic autoimmune disease other than RA
- Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16
- Active fibromyalgia that makes appropriate assessment of RA disease activity challenging in the opinion of the Investigator
- RA patients functional status class IV according to the American College of Rheumatology (ACR) 1991 criteria (i.e., largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair)
- Patients with severe chronic or recurrent viral, bacterial, parasitic or fungal infections
- History of active hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection
- Any identified confirmed congenital or acquired immunodeficiency
- Abnormal laboratory test results
- Other unstable somatic diseases (apart from RA) that can increase the probability of adverse events during the study or can influence the estimation of symptom manifestation of RA; mask, enhance or alter the symptoms of RA or cause clinical or laboratory symptoms similar to that of RA
- Major surgery within 28 days prior to randomization, or planned major surgery (e.g., elective joint replacement surgery) during the trial
- Any mental disorder
- Myocardial infarction within less than 6 months prior to participation in the study
- Severe central or peripheral nervous system diseases
- Chronic drug or alcohol abuse
- Known hypersensitivity to any components of the medications used in the study
- Acute forms of any infectious diseases or history of chronic infections with severe clinical manifestations
- Presence of malignant neoplasm, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ and any malignancy with complete remission of more than 5 years
- German sites: Patients who are institutionalized due to regulatory or juridical order
- German sites: Patients who are occupationally or medically dependent on the Sponsor, the Investigator, or the medical site


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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]

Intervention(s)

Product Name: RO7123520
Product Code: RO7123520/F03-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not available
Current Sponsor code: RO7123520/F03-01
Other descriptive name: RO7123520
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: •To assess the safety, tolerability and efficacy of RO7123520 as adjunctive treatment with Methotrexate (MTX) and anti- Tumor necrosis factor-a (TNF-a) therapy in patients with moderately to severely active RA with an anti-TNF-a inadequate response (Study Parts 1,2, 3)

Timepoint(s) of evaluation of this end point: 1-2. Up to 36 weeks (including German sites)
3. Baseline (Day 1), Week 4, Week 12, Week 16, Week 24, and Week 28
4. Baseline, Week 2, Week, 4, Week, 6, Week 12, Week, 16, Week 24,
and Week 28
5. Baseline, Week 12, Week 16, and Week 28
6. Screening (Day -7 to -1), Week 12, and Week 24
7. Week 12

Primary end point(s): 1. Incidence of adverse events
2. Incidence of ECG, vital signs and laboratory abnormalities
3. Assessment of bone remodeling and cartilage markers
4. Assessment of blood cell markers
5. Anti-drug antibodies (ADA)
6. Bone mineral density by dual energy X-ray absorptiometry (DEXA) scans
7. Proportion of patients achieving an ACR50 response at Week 12

Secondary Objective: •To assess the dose-ranging efficacy of RO7123520 (Study Part 3)
•To assess the exposure versus response relationship and immunogenicity of RO7123520 (Study Parts 1,2, 3)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-2. Baseline and Week 12
3-7. Week 12
8. Baseline and Week 12
9. Baseline, Week 12, and Week 24 (for synovial fluid ); Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28 (for serum)

Secondary end point(s): 1. Change from baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
2. Change from baseline in Disease Activity Score (DAS28) at Week 12
3. Proportion of patients achieving DAS28 remission at Week 12
4. Proportion of patients achieving CDAI remission at Week 12
5. Proportion of patients achieving an ACR20 response at Week 12
6. Proportion of patients achieving an ACR70 response at Week 12
7. Simple Disease Activity Index (SDAI) Score at Week 12
8. Change from baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
9. Serum and synovial fluid concentration of RO7123520

Secondary ID(s)

BP39261

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd