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

NCT02795299 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: BRB-008-003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (4)

Gerilimzumab 5/2 mg/Methotrexate/folate

ACTIVE COMPARATOR

• 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

Drug: Gerilimzumab; Drug: Methotrexate; Drug: Folic Acid

Gerilimzumab 10/5mg/Methotrexate/folate

ACTIVE COMPARATOR

• 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

Drug: Gerilimzumab; Drug: Methotrexate; Drug: Folic Acid

Gerilimzumab 20/10mg/Methotrexate/folate

ACTIVE COMPARATOR

• 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

Drug: Gerilimzumab; Drug: Methotrexate; Drug: Folic Acid

Placebo/Methotrexate/folate

PLACEBO COMPARATOR

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

Drug: Methotrexate; Drug: Folic Acid; Drug: Placebo

Interventions

Gerilimzumab DRUG

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.

Gerilimzumab 10/5mg/Methotrexate/folate; Gerilimzumab 20/10mg/Methotrexate/folate; Gerilimzumab 5/2 mg/Methotrexate/folate

Methotrexate DRUG

Methotrexate (MTX) to be administered once a week every week during the treatment period.

Gerilimzumab 10/5mg/Methotrexate/folate; Gerilimzumab 20/10mg/Methotrexate/folate; Gerilimzumab 5/2 mg/Methotrexate/folate; Placebo/Methotrexate/folate

Folic Acid DRUG

Acid folic (folate) 1mg to be administered once daily during the treatment period.

Gerilimzumab 10/5mg/Methotrexate/folate; Gerilimzumab 20/10mg/Methotrexate/folate; Gerilimzumab 5/2 mg/Methotrexate/folate; Placebo/Methotrexate/folate

Placebo DRUG

10 mM acetate, 9% (w/v) sucrose, and 0.006% (w/v) polysorbate 20 at pH 5.2 ± 0.3

Placebo/Methotrexate/folate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bird Rock Bio, Inc.: lead
• Techtrials Pesquisa e Tecnologia Ltda: collaborator
• Pharmagenix: collaborator

Related Publications (4)

• 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. English, Portuguese.

  PMID: 22885417 RESULT

• 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.

  PMID: 22150039 RESULT

• 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.

  PMID: 24699939 RESULT

• 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.

  PMID: 22328739 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mauro Keiserman

  LMK - Serviços Medicos Sociedade Simples, Porto Alegre, Rio Grande do Sul, Brazil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: June 10, 2016
• Study Start: January 1, 2018
• Primary Completion: May 1, 2019
• Study Completion: September 1, 2019
• Last Updated: July 11, 2018

Record last verified: 2018-01