A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)

• ClinicalTrials.gov Identifier: NCT02277444
• Recruitment Status: Active, not recruiting
• First Posted: October 29, 2014
• Results First Posted: November 18, 2020
• Last Update Posted: May 6, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The purpose of this study is to evaluate the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of golimumab administered intravenously (IV) to pediatric participants with polyarticular (affects 5 or more joints) juvenile (an onset before age 16) idiopathic (of unknown cause) arthritis (joint pain) (pJIA) manifested by greater than or equal to (>=) 5 joints with active arthritis despite methotrexate (MTX) therapy for >= 2 months.

Condition or disease	Intervention/treatment	Phase
Arthritis, Juvenile	Drug: Golimumab; Drug: Methotrexate	Phase 3

Detailed Description:

This is a single arm, Open-label (all people know the identity of the intervention), multi-center (when more than one hospital or medical school team work on a medical research study) study to determine the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), efficacy (effectiveness) and safety of intravenous golimumab in participants with pJIA despite current treatment with methotrexate (MTX). The study will consist of 3 parts: Screening Phase (6 weeks); an Open-label Treatment Phase (consists of golimumab and MTX treatment for 52 weeks, wherein after Week 28, MTX dose change is allowed); Long-term Extension Phase (after Week 52 through Week 252) and Extended Treatment Period (after week 252). The maximal study duration for a participant will not exceed 832 weeks. All the eligible participants will be administered golimumab IV infusion and commercial MTX. Blood samples will be collected for evaluation of pharmacokinetics of study treatment. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα Antibody, in Pediatric Subjects With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy
• Actual Study Start Date: December 17, 2014
• Actual Primary Completion Date: July 9, 2018
• Estimated Study Completion Date: February 6, 2032

Arms and Interventions

Arm

Intervention/treatment

Experimental: Golimumab + Methotrexate; Participants will receive 80 milligram per meter square (mg/m^2) as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks thereafter up to Week 244, along with commercial methotrexate (MTX) weekly through Week 28 at the same Body Surface Area (BSA)-based dosage (10 to 30 mg/m^2 per week for participants with BSA less than [<] 1.67 meter square (m^2), or minimum of 15 mg/week for participants with BSA greater than or equal to [>=] 1.67 m^2) as at the time of study entry. At Week 252, participants who meet the criteria for the optional Extended Treatment Period (ETP) may continue treatment with golimumab 80 mg/m^2 every 8 weeks after completion of the Week 252 assessments.

Drug: Golimumab; Golimumab 80 mg/m^2 IV infusion at Weeks 0, 4, and every 8 weeks through Week 244. At Week 252, participants who meet the criteria for the optional Extended Treatment Period (ETP) may continue treatment with golimumab 80 mg/m^2 every 8 weeks after completion of the Week 252 assessments.; Other Name: Simponi Aria; Drug: Methotrexate; Methotrexate BSA-based dose (10 to 30 mg/m^2 per week for participants with BSA <1.67 m^2, or minimum of 15 mg/week for participants with BSA >=1.67 m^2) weekly at least through Week 28.

Outcome Measures

Primary Outcome Measures :

1. Serum Trough Concentration (C-trough) of Golimumab [ Time Frame: Week 28 ]
   Serum golimumab trough concentration at Week 28 was reported.
2. Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28 [ Time Frame: Week 28 ]
   AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).

Secondary Outcome Measures :

1. Serum Trough Concentration (C-trough) at Week 52 [ Time Frame: Week 52 ]
   Serum golimumab trough concentration at Week 52 was reported.
2. Baysesian Area Under Curve at Steady State (AUCss) at Week 52 [ Time Frame: Week 52 ]
   AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis must be made per Juvenile Idiopathic Arthritis (JIA) International League of Associations for Rheumatology (ILAR) diagnostic criteria and the onset of disease must have been before the participant's 16th birthday
• Failure or inadequate response to at least a 2 month course of methotrexate (MTX) before screening
• Participants must have greater than or equal to (>=) 5 joints with active arthritis at screening and at Week 0 as defined by American College of Rheumatology (ACR) criteria (that is, a joint with either swelling, or in the absence of swelling, limited range of motion associated with pain on motion or tenderness)
• Participants must have a screening C-reactive protein (CRP) of >=0.1 milligram (mg)/deciliter (dL) with the exception of approximately 30 percent (%) of the study population
• Participants must have active polyarticular juvenile idiopathic arthritis (pJIA) despite current use of oral, intramuscular, or subcutaneous MTX for >=2 months before screening. For participants with body surface area (BSA) less than (<)1.67 meter square (m^2), the MTX dose must be between 10 to 30 milligram per meter square (mg/m^2) per week and stable for >=4 weeks before screening. For participants with BSA >=1.67 m^2, the MTX dose must be a minimum of 15 mg/week and must be stable for >=4 weeks before screening. In situations where there is documented intolerance of doses greater than (>)10 mg/m^2 weekly (for participants with BSA <1.67 m^2) or >=15 mg/week (for participants with BSA >=1.67 m^2); or where documented country or site regulations prohibit use of >=15 mg of MTX per week in participants with BSA >=1.67 m^2, participants may be entered into the trial on a lower dose of MTX

Exclusion Criteria:

• Participant has initiated disease-modifying antirheumatic drugs (DMARDs) and/or immunosuppressive therapy within 4 weeks prior to first study agent administration
• Participant has been treated with intra-articular, intramuscular or intravenous corticosteroids (including intramuscular corticotropin) during the 4 weeks before first study agent administration
• Participant has been treated with any therapeutic agent targeted at reducing Interleukin (IL)-12 or IL 23, including but not limited to ustekinumab and ABT-874, within 3 months before first study agent administration
• Participant has been treated with natalizumab, efalizumab, or therapeutic agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) during the 12 months before first study agent administration, or have evidence at screening of persistent depletion of the targeted lymphocyte after receiving any of these agents
• Participant has been treated with alefacept within 3 months before first study agent administration
• If a participant has been previously treated with an anti-tumor necrosis factor alpha (TNF alpha) agent, the reason for discontinuation of the anti-TNF alpha agent cannot have been a severe or serious adverse event consistent with the class of anti-TNF alpha agents

Contacts and Locations

Locations

United States, California

San Diego, California, United States

United States, Illinois

Chicago, Illinois, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, New Jersey

Hackensack, New Jersey, United States

United States, New York

New Hyde Park, New York, United States

United States, North Carolina

Durham, North Carolina, United States

Hickory, North Carolina, United States

United States, Ohio

Avon, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

United States, Oregon

Portland, Oregon, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, Texas

Austin, Texas, United States

United States, Utah

Salt Lake City, Utah, United States

Argentina

Buenos Aires, Argentina

Rosario, Argentina

San Miguel De Tucuman, Argentina

Brazil

Botucatu, Brazil

Campinas, Brazil

Porto Alegre, Brazil

Rio de Janeiro, Brazil

Sao Paulo, Brazil

Canada, Alberta

Calgary, Alberta, Canada

Canada, Ontario

Toronto, Ontario, Canada

Canada, Quebec

Montreal, Quebec, Canada

Chile

Región Metropolitana De Santia, Chile

Israel

Haifa, Israel

Kfar-Saba, Israel

Petach-Tikva, Israel

Mexico

Chihuahua, Mexico

Ciudad De Mexico, Mexico

Guadalajara, Mexico

Russian Federation

Mosco2, Russian Federation

Saint Petersburg, Russian Federation

Saratov, Russian Federation

Togliatti, Russian Federation

Ufa, Russian Federation

South Africa

Cape Town, South Africa

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] December 16, 2019

Statistical Analysis Plan  [PDF] August 1, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leu JH, Shiff NJ, Clark M, Bensley K, Lomax KG, Berezny K, Nelson RM, Zhou H, Xu Z. Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations. Paediatr Drugs. 2022 Nov;24(6):699-714. doi: 10.1007/s40272-022-00533-y. Epub 2022 Sep 28.

Ruperto N, Brunner HI, Pacheco-Tena C, Louw I, Vega-Cornejo G, Spindler AJ, Kingsbury DJ, Schmeling H, Borzutzky A, Cuttica R, Inman CJ, Malievskiy V, Scott C, Keltsev V, Terreri MT, Viola DO, Xavier RM, Fernandes TAP, Velazquez MDRM, Henrickson M, Clark MB, Bensley KA, Li X, Lo KH, Leu JH, Hsu CH, Hsia EC, Xu Z, Martini A, Lovell DJ; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO). Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2021 Oct 2;60(10):4495-4507. doi: 10.1093/rheumatology/keab021.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02277444
• Other Study ID Numbers: CR105178; CNTO148JIA3003 ( Other Identifier: Janssen Research & Development, LLC ); 2015-004804-47 ( EudraCT Number )
• First Posted: October 29, 2014
• Results First Posted: November 18, 2020
• Last Update Posted: May 6, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:

Methotrexate; Anti-TNFα Antibody; Golimumab; Pediatric Participants

Additional relevant MeSH terms:

Arthritis; Arthritis, Juvenile; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Golimumab; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents