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Study Evaluating Gerilimzumab´s Safety/Efficacy for Patients MTX or TNFα Antagonist Failed in Rheumatoid Arthritis

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Status and phase

Withdrawn
Phase 2

Conditions

Rheumatoid Arthritis

Treatments

Drug: Folic Acid
Drug: Methotrexate
Drug: Gerilimzumab
Drug: Placebo

Study type

Interventional

Funder types

Industry
Other

Identifiers

NCT02795299
BRB-008-003

Details and patient eligibility

About

Phase 2 Study Evaluating Gerilimzumab's Safety/Efficacy for Patients with an Inadequate Response to MTX or a TNFα Antagonist in Rheumatoid Arthritis.

Full 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.

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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/exclusion criteria are met.

  2. Diagnosis of any other arthritis (e.g., psoriatic arthritis or ankylosing spondylitis)

  3. Secondary, non-inflammatory type of arthritis (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion could interfere with the evaluation of the effect of study medication on the subjects primary diagnosis of RA

    Concomitant medication/therapy exclusions:

  4. Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (except TNFα inhibitors (as described above) prior to screening;

  5. Any prior exposure to natalizumab, efalizumab, rituximab, tocilizumab, or abatacept, or tofacitinib or any other Janus kinase [JAK]-inhibitors, or anti IL-1 therapies;

  6. Within 30 days prior to enrollment, have received any of the following for the treatment of underlying disease:

    • Non-biologic therapies (e.g., cyclosporine, tacrolimus, thalidomide)
  7. Have received prior approved or Investigational therapy blocking the interleukin-6 (IL-6) pathway, at any time

  8. Have received any live (includes attenuated) vaccination within 60 days prior to screening (e.g., injectable influenza and pneumococcal vaccines are allowed, but nasal influenza vaccine is not) or anticipate needing any such vaccines for the duration of the study until 30 days after study treatment discontinuation

  9. Subject has previously received any other investigational (either approved or unapproved) drug within 30 days or 5 half-lives (whichever is longer) prior to the screening visit

  10. History of tuberculosis (patients with previous TB treated with local standard of care and with documentation of completion of this therapy will be allowed)

  11. Any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation)

  12. Positive for Hepatitis BSAg or Hepatitis C virus

  13. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 4 weeks of screening with last dose of antibiotics received within 2 weeks of screening

  14. History of malignancy within the 5 years prior to Screening except for adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix

  15. History of diverticulitis, diverticulosis, or intestinal perforation

  16. History of anaphylactic reactions to biologic therapy requiring medical attention.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

0 participants in 4 patient groups, including a placebo group

Gerilimzumab 5/2 mg/Methotrexate/folate
Active Comparator group
Description:
• 5 mg gerilimzumab loading dose followed by 2 mg gerilimzumab every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily
Treatment:
Drug: Folic Acid
Drug: Methotrexate
Drug: Gerilimzumab
Gerilimzumab 10/5mg/Methotrexate/folate
Active Comparator group
Description:
• 10 mg gerilimzumab loading dose followed by 5 mg gerilimzumab every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily
Treatment:
Drug: Folic Acid
Drug: Methotrexate
Drug: Gerilimzumab
Gerilimzumab 20/10mg/Methotrexate/folate
Active Comparator group
Description:
• 20 mg gerilimzumab loading dose followed by 10 mg gerilimzumab every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily
Treatment:
Drug: Folic Acid
Drug: Methotrexate
Drug: Gerilimzumab
Placebo/Methotrexate/folate
Placebo Comparator group
Description:
• Placebo every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily
Treatment:
Drug: Folic Acid
Drug: Placebo
Drug: Methotrexate

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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