GO-VIVA: 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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02277444
• Collaborator: (none)
• Enrollment: 130
• Locations: 38
• Arm: 1
• Anticipated Duration (Months): 205.7
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

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
• 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: Dec 17, 2014
• Actual Primary Completion Date: Jul 9, 2018
• Anticipated Study Completion Date: Feb 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 Names: 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 [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 [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 [Week 52]

   Serum golimumab trough concentration at Week 52 was reported.

2. Baysesian Area Under Curve at Steady State (AUCss) at Week 52 [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1		San Diego	California	United States
2		Chicago	Illinois	United States
3		Boston	Massachusetts	United States
4		Hackensack	New Jersey	United States
5		New Hyde Park	New York	United States
6		Durham	North Carolina	United States
7		Avon	Ohio	United States
8		Cincinnati	Ohio	United States
9		Cleveland	Ohio	United States
10		Portland	Oregon	United States
11		Philadelphia	Pennsylvania	United States
12		Austin	Texas	United States
13		Salt Lake City	Utah	United States
14		Buenos Aires		Argentina
15		San Miguel De Tucuman		Argentina
16		Santa Fe		Argentina
17		Botucatu		Brazil
18		Campinas		Brazil
19		Porto Alegre		Brazil
20		Rio de Janeiro		Brazil
21		Sao Paulo		Brazil
22		Calgary	Alberta	Canada
23		Toronto	Ontario	Canada
24		Montreal	Quebec	Canada
25		Región Metropolitana De Santia		Chile
26		Haifa		Israel
27		Kfar-Saba		Israel
28		Petach Tikvah		Israel
29		Chihuahua		Mexico
30		Ciudad De Mexico		Mexico
31		Guadalajara		Mexico
32		Mosco2		Russian Federation
33		Saint Petersburg		Russian Federation
34		Saratov		Russian Federation
35		Togliatti		Russian Federation
36		Ufa		Russian Federation
37		Cape Town Rondebosch N/a		South Africa
38		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)

• Study Protocol - Dec 16, 2019
• Statistical Analysis Plan - Aug 1, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02277444
• Other Study ID Numbers: CR105178; CNTO148JIA3003; 2015-004804-47
• First Posted: Oct 29, 2014
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• 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; Golimumab; Methotrexate

Study Results

Participant Flow

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Period Title: Overall Study
STARTED	130
Treated	127
COMPLETED	0
NOT COMPLETED	130

Baseline Characteristics

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Overall Participants	127
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.6 (3.85)
Sex: Female, Male (Count of Participants)
Female	93 73.2%
Male	34 26.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	63 49.6%
Not Hispanic or Latino	62 48.8%
Unknown or Not Reported	2 1.6%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	4 3.1%
Asian	1 0.8%
Black or African American	5 3.9%
More than one race	4 3.1%
Other	28 22%
White	85 66.9%
Region of Enrollment (Count of Participants)
ARGENTINA	18 14.2%
BRAZIL	16 12.6%
CANADA	7 5.5%
CHILE	7 5.5%
ISRAEL	2 1.6%
MEXICO	25 19.7%
RUSSIAN FEDERATION	14 11%
SOUTH AFRICA	15 11.8%
UNITED STATES	23 18.1%

Outcome Measures

1. Primary Outcome

Title	Serum Trough Concentration (C-trough) of Golimumab
Description	Serum golimumab trough concentration at Week 28 was reported.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Measure Participants	87
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	0.50 (0.427)

2. Primary Outcome

Title	Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28
Description	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).
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis.

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Measure Participants	127
Median (Full Range) [micrograms*day/milliliter (mcg*day/mL)]	399

3. Secondary Outcome

Title	Serum Trough Concentration (C-trough) at Week 52
Description	Serum golimumab trough concentration at Week 52 was reported.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Measure Participants	95
Mean (Standard Deviation) [mcg/mL]	0.52 (0.475)

4. Secondary Outcome

Title	Baysesian Area Under Curve at Steady State (AUCss) at Week 52
Description	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).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis.

Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
Measure Participants	127
Median (Full Range) [mcg*day/mL]	421

Adverse Events

Time Frame	Up to Week 52
Adverse Event Reporting Description	Safety evaluable analysis set included all participants who received at least 1 dose of study agent.
Arm/Group Title	Golimumab
Arm/Group Description	Participants received 80 milligrams per meter square (mg/m^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks (q8w) till Week 52. Participants also received 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 time of study entry. After Week 28, changes in MTX administration were permitted.
All Cause Mortality
	Golimumab
	Affected / at Risk (%)	# Events
Total	0/127 (0%)
Serious Adverse Events
	Golimumab
	Affected / at Risk (%)	# Events
Total	9/127 (7.1%)
Infections and infestations
Cellulitis	1/127 (0.8%)
Herpes Zoster Disseminated	1/127 (0.8%)
Infective Exacerbation of Bronchiectasis	1/127 (0.8%)
Pneumonia	1/127 (0.8%)
Pneumonia Streptococcal	1/127 (0.8%)
Sepsis	1/127 (0.8%)
Varicella	1/127 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis Fungoides	1/127 (0.8%)
Psychiatric disorders
Suicidal Ideation	1/127 (0.8%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/127 (0.8%)
Other (Not Including Serious) Adverse Events
	Golimumab
	Affected / at Risk (%)	# Events
Total	71/127 (55.9%)
Gastrointestinal disorders
Abdominal Pain	8/127 (6.3%)
Nausea	11/127 (8.7%)
Vomiting	10/127 (7.9%)
Infections and infestations
Nasopharyngitis	23/127 (18.1%)
Upper Respiratory Tract Infection	27/127 (21.3%)
Investigations
Alanine Aminotransferase Increased	7/127 (5.5%)
Musculoskeletal and connective tissue disorders
Juvenile Idiopathic Arthritis	14/127 (11%)
Nervous system disorders
Headache	14/127 (11%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.