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

Primary Purpose

Rheumatoid Arthritis

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gerilimzumab
Methotrexate
Folic Acid
Placebo
Sponsored by
Bird Rock Bio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Active Comparator

    Active Comparator

    Active Comparator

    Placebo Comparator

    Arm Label

    Gerilimzumab 5/2 mg/Methotrexate/folate

    Gerilimzumab 10/5mg/Methotrexate/folate

    Gerilimzumab 20/10mg/Methotrexate/folate

    Placebo/Methotrexate/folate

    Arm 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

    • 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

    • 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

    • Placebo every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily

    Outcomes

    Primary Outcome Measures

    Change from baseline in mean DAS28-CRP (Disease Activity Score 28 using the C-Reactive Protein value)

    Secondary Outcome Measures

    The proportion of patients meeting the ACR20 (American College of Rheumatology 20%) response criteria at Week 12

    Full Information

    First Posted
    May 2, 2016
    Last Updated
    July 9, 2018
    Sponsor
    Bird Rock Bio, Inc.
    Collaborators
    Techtrials Pesquisa e Tecnologia Ltda, Pharmagenix
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02795299
    Brief Title
    Study Evaluating Gerilimzumab´s Safety/Efficacy for Patients MTX or TNFα Antagonist Failed in Rheumatoid Arthritis
    Official Title
    Phase 2, Rand, Placebo-Controlled, Double-Blind, Dose Ranging Study to Evaluating Safety/Efficacy of Gerilimzumab in Patients With Moderately to Severely Active Rheumatoid Arthritis Inadequately Treated With Methotrexate or TNFα Antagonist
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2018
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study not started due to Sponsor decision to not move forward with compound.
    Study Start Date
    January 2018 (Anticipated)
    Primary Completion Date
    May 2019 (Anticipated)
    Study Completion Date
    September 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Bird Rock Bio, Inc.
    Collaborators
    Techtrials Pesquisa e Tecnologia Ltda, Pharmagenix

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rheumatoid Arthritis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Gerilimzumab 5/2 mg/Methotrexate/folate
    Arm Type
    Active Comparator
    Arm 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
    Arm Title
    Gerilimzumab 10/5mg/Methotrexate/folate
    Arm Type
    Active Comparator
    Arm 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
    Arm Title
    Gerilimzumab 20/10mg/Methotrexate/folate
    Arm Type
    Active Comparator
    Arm 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
    Arm Title
    Placebo/Methotrexate/folate
    Arm Type
    Placebo Comparator
    Arm Description
    • Placebo every 8 weeks + 15-25 mg Methotrexate every week + 1 mg folic acid once daily
    Intervention Type
    Drug
    Intervention Name(s)
    Gerilimzumab
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Methotrexate
    Intervention Description
    Methotrexate (MTX) to be administered once a week every week during the treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    Folic Acid
    Intervention Description
    Acid folic (folate) 1mg to be administered once daily during the treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    10 mM acetate, 9% (w/v) sucrose, and 0.006% (w/v) polysorbate 20 at pH 5.2 ± 0.3
    Primary Outcome Measure Information:
    Title
    Change from baseline in mean DAS28-CRP (Disease Activity Score 28 using the C-Reactive Protein value)
    Time Frame
    to be applied in weeks - 6, -2, -1, 0, 4, 8, 12 and 16
    Secondary Outcome Measure Information:
    Title
    The proportion of patients meeting the ACR20 (American College of Rheumatology 20%) response criteria at Week 12
    Time Frame
    to be applied in weeks -6, 0, 4, 8, 12 and 16

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key Inclusion Criteria Each patient must meet the following inclusion criteria to be enrolled in the study: Men or women, ages 18 to 80 years, inclusive; 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; 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; 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; Demonstrated an inadequate response to previous or current MTX treatment and/or a single TNFα inhibitor; C-reactive Protein (CRP) above the ULN for the central laboratory at the time of screening; Positive Cyclic Citrullinated Peptide (CCP) antibody or Rheumatoid Factor (RF) from the central laboratory at the screening visit; 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) 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 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 Women of child-bearing potential must use effective contraception for the duration of the study until 180 days after study treatment discontinuation 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 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. Diagnosis of any other arthritis (e.g., psoriatic arthritis or ankylosing spondylitis) 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: Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (except TNFα inhibitors (as described above) prior to screening; Any prior exposure to natalizumab, efalizumab, rituximab, tocilizumab, or abatacept, or tofacitinib or any other Janus kinase [JAK]-inhibitors, or anti IL-1 therapies; 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) Have received prior approved or Investigational therapy blocking the interleukin-6 (IL-6) pathway, at any time 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 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 History of tuberculosis (patients with previous TB treated with local standard of care and with documentation of completion of this therapy will be allowed) Any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation) Positive for Hepatitis BSAg or Hepatitis C virus 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 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 History of diverticulitis, diverticulosis, or intestinal perforation History of anaphylactic reactions to biologic therapy requiring medical attention.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mauro Keiserman
    Organizational Affiliation
    LMK - Serviços Medicos Sociedade Simples, Porto Alegre, Rio Grande do Sul, Brazil
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22885417
    Citation
    Pereira IA, Mota LM, Cruz BA, Brenol CV, Fronza LS, Bertolo MB, Freitas MV, Silva NA, Louzada-Junior P, Giorgi RD, Lima RA, Pinheiro Gda R; Brazilian Society of Rheumatology. 2012 Brazilian Society of Rheumatology Consensus on the management of comorbidities in patients with rheumatoid arthritis. Rev Bras Reumatol. 2012 Aug;52(4):474-95. Erratum In: Rev Bras Reumatol. 2012 Oct;52(5):815. English, Portuguese.
    Results Reference
    result
    PubMed Identifier
    22150039
    Citation
    McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NEJMra1004965. No abstract available.
    Results Reference
    result
    PubMed Identifier
    24699939
    Citation
    Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.
    Results Reference
    result
    PubMed Identifier
    22328739
    Citation
    Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu LA, Liu Y, Smith J. A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis. 2012 Jul;71(7):1183-9. doi: 10.1136/annrheumdis-2011-200704. Epub 2012 Feb 10.
    Results Reference
    result

    Learn more about this trial

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

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