Rheumatoid Arthritis
Conditions
Brief summary
Phase 2 Study Evaluating Gerilimzumab's Safety/Efficacy for Patients with an Inadequate Response to MTX or a TNFα Antagonist in Rheumatoid Arthritis.
Detailed description
The trial will include adult patients 18-80 years of age with active disease who have demonstrated an inadequate response to treatment with MTX. Eligible patients will enter a 6-week screening period receiving 15-25 mg MTX QWK (patients will remain on their current dose and route of administration of MTX through the screening period). Patients on a dose of MTX less than 15mg QWK will have their dose of MTX increased to 15mg QWK at the initial screening visit) followed by randomization in a 1:1:1:1 ratio to 1 of 3 doses of gerilimzumab (5, 10, or 20 mg loading dose followed by 2 mg, 5 mg or 10 mg of gerilimzumab Q8W) plus MTX, or placebo plus MTX for 12 weeks of treatment. Gerilimzumab and placebo will be administered as SC injections Q8W; MTX will continue to be administered as by same route of administration (tablets, SC, or IM injection) QWK.
Interventions
DRUGGerilimzumab
Either Gerilimzumab 5 mg followed by 2 mg, or Gerilimzumab 10 mg followed by 5 mg or Gerilimzumab 20 mg followed by 10 mg are to be administered once every 8 weeks during the treatment period of the study.
DRUGMethotrexate
Methotrexate (MTX) to be administered once a week every week during the treatment period.
DRUGFolic Acid
Acid folic (folate) 1mg to be administered once daily during the treatment period.
DRUGPlacebo
10 mM acetate, 9% (w/v) sucrose, and 0.006% (w/v) polysorbate 20 at pH 5.2 ± 0.3
Sponsors
Techtrials Pesquisa e Tecnologia Ltda
Pharmagenix
Bird Rock Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria Each patient must meet the following inclusion criteria to be enrolled in the study: 1. Men or women, ages 18 to 80 years, inclusive; 2. Diagnosis of moderately to severely active RA for at least 3 months prior to screening as according to 2010 EULAR/ACR classification criteria for at least 3 months prior to screening with ACR functional class I-III; 3. Have active RA with ≥4 swollen and ≥4 tender joints (28 joint count) throughout the screening period (all visits) and baseline visit at Week 0 baseline. Must meet above criteria in order to enter screening phase at all screening visits to be randomized; 4. Current treatment with stable dose of oral MTX (i.e., 15-25 mg/week for \>6 weeks) prior to screening. Patients will remain on their current dose and route of administration of MTX through the screening period. Patients must also remain on a stable dose and route of administration of MTX and folic acid supplementation throughout the randomized treatment phase of the study. Patients on a dose of MTX \<15 mg QWK may have their dose of MTX increased to 15mg QWK at the initial screening visit providing that they meet all other entry criteria; 5. Demonstrated an inadequate response to previous or current MTX treatment and/or a single TNFα inhibitor; 6. C-reactive Protein (CRP) above the ULN for the central laboratory at the time of screening; 7. Positive Cyclic Citrullinated Peptide (CCP) antibody or Rheumatoid Factor (RF) from the central laboratory at the screening visit; 8. Previous treatment with a single TNFα antagonist is permitted, providing there has been: * An inadequate response to an approved or investigational: TNFα antagonist despite completing an induction regimen with any approved or experimental TNFα antagonist per the current labeling, study protocol or institutional standard of care * Recurrence of symptoms during maintenance dosing with a TNFα antagonist following prior clinical benefit(discontinuation despite clinical benefit does not qualify) * History of intolerance to a TNFα antagonist (including but not limited to infusion or injection related reaction, demyelination, congestive heart failure or serious infection) 9. Considered to be in stable health in the opinion of the Investigator, as determined by: * A pre-study physical examination with no clinically significant abnormalities aside from those related to rheumatoid disease * Vital signs (VS): heart rates at screening must be ≥ 50 bpm; and systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 90 and ≥ 55, respectively at all screening visits * Liver function tests (ALT/AST, bilirubin and Alkaline phosphatase) \<2X the upper limit of normal) at all screening visits 10. Subject is not pregnant (negative pregnancy test) or nursing and is not planning pregnancy or initiation of breast-feeding over the duration of the study 11. Women of child-bearing potential must use effective contraception for the duration of the study until 180 days after study treatment discontinuation 12. Men who have sexual relationships with women of child-bearing potential will agree to use an effective means of contraception for the duration of the study until 60 days after study treatment discontinuation. In addition, men must agree not to donate sperm for the duration of the study until 60 days after study treatment discontinuation. Key
Exclusion criteria
1. History of an autoimmune disease other than RA or with significant systemic involvement secondary to RA. Patients with a history of diabetes and or thyroiditis are eligible to participate if all other inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in mean DAS28-CRP (Disease Activity Score 28 using the C-Reactive Protein value) | to be applied in weeks - 6, -2, -1, 0, 4, 8, 12 and 16 |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of patients meeting the ACR20 (American College of Rheumatology 20%) response criteria at Week 12 | to be applied in weeks -6, 0, 4, 8, 12 and 16 |
Outcome results
None listed