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

NCT ID: NCT02795299

Last Updated: 2018-07-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-31
• Study Completion Date: 2019-09-30

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Gerilimzumab 5/2 mg/Methotrexate/folate

• 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

Group Type: ACTIVE_COMPARATOR

Gerilimzumab

Intervention Type: 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.

Methotrexate

Intervention Type: DRUG

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

Folic Acid

Intervention Type: DRUG

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

Gerilimzumab 10/5mg/Methotrexate/folate

• 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

Group Type: ACTIVE_COMPARATOR

Gerilimzumab

Intervention Type: 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.

Methotrexate

Intervention Type: DRUG

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

Folic Acid

Intervention Type: DRUG

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

Gerilimzumab 20/10mg/Methotrexate/folate

• 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

Group Type: ACTIVE_COMPARATOR

Gerilimzumab

Intervention Type: 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.

Methotrexate

Intervention Type: DRUG

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

Folic Acid

Intervention Type: DRUG

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

Placebo/Methotrexate/folate

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

Group Type: PLACEBO_COMPARATOR

Methotrexate

Intervention Type: DRUG

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

Folic Acid

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

Gerilimzumab

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

Methotrexate

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

Intervention Type: DRUG

Folic Acid

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Techtrials Pesquisa e Tecnologia Ltda

UNKNOWN

Sponsor Role: collaborator

Pharmagenix

UNKNOWN

Sponsor Role: collaborator

Bird Rock Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mauro Keiserman

Role: PRINCIPAL_INVESTIGATOR

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

References

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.

Reference Type: RESULT

PMID: 22885417 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22150039 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24699939 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22328739 (View on PubMed)

Other Identifiers

BRB-008-003

Identifier Type: -

Identifier Source: org_study_id