Safety, Efficacy, and Pharmacokinetics of Adalimumab in Japanese Children With Juvenile Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00690573
• Recruitment Status: Completed
• First Posted: June 4, 2008
• Results First Posted: April 1, 2011
• Last Update Posted: September 10, 2012
• Sponsor: Abbott
• Collaborator: Eisai Co., Ltd.
• Information provided by (Responsible Party): Abbott

Study Description

Brief Summary:

To evaluate efficacy, safety and pharmacokinetics of adalimumab in Japanese children with Polyarticular Juvenile Rheumatoid Arthritis

Condition or disease	Intervention/treatment	Phase
Juvenile Rheumatoid Arthritis	Biological: Adalimumab	Phase 3

Detailed Description:

This was an open-label long-term study that was completed following study drug approval in Japan for the treatment of JRA. Data are presented through Week 144 and for the final visit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Rheumatoid Arthritis
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adalimumab	Biological: Adalimumab; Adalimumab administered subcutaneously every other week, with dosage determined by body weight at study entry (20 mg for children weighing less than 30 kg, 40 mg for children weighing 30 kg or more).; Other Name: adalimumab, ABT-D2E7, Humira

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16 [ Time Frame: Week 16 ]
   Response defined as at least 30% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 30% worsening in not more than 1 JRA criterion, compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion [LOM] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.

Secondary Outcome Measures :

1. Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 [ Time Frame: Week 16 ]
   Response defined as at least 50/70% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 50/70% worsening in not more than 1 JRA criterion compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion [LOM] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
2. Number of Subjects Achieving PedACR 30/50/70 Responses [ Time Frame: Week 2, 4, 8, and 24, every 12 weeks from Week 24 to Week 60, and every 24 weeks from Week 72 to the final visit ]
3. Mean Serum Adalimumab Concentration [ Time Frame: Week 2, 4, 8, 16, and 24, and every 12 weeks up to Week 60 ]
   Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method based on a double-antigen technique. Concentrations are reported as micrograms per milliliter (mcg/mL).
4. Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) [ Time Frame: Week 24 and Week 60 ]
   Serum samples with adalimumab concentration below 2 mcg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 20 ng/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose.

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

• Diagnosis of polyarticular juvenile rheumatoid arthritis (JRA) according to the criteria of the American College on Rheumatology (ACR)
• Disease activity inadequately controlled by nonsteroidal anti-inflammatory drugs (NSAIDs) or methotrexate (MTX)
• Presence at screening of at least 5 swollen joints (not due to deformity) and at least 3 joints with limitation of passive motion with pain by passive motion or/and pain by pressure (tenderness)
• Stable dosage of MTX for at least 12 weeks prior to the screening visit or discontinuation of MTX at least 14 days prior to baseline visit (Day 1)
• Discontinuation of disease-modifying antirheumatic drugs (DMARDs) other than MTX at least 28 days before screening visit

Exclusion Criteria

• History of inflammatory joint disease other than JRA
• Functional class IV JRA by ACR criteria
• Clinically significant cardiac disease or laboratory abnormalities
• Any subject who is considered by the investigator, for any reason, to be an unsuitable candidate for the study

Contacts and Locations

Locations

Japan

Site Reference ID/Investigator# 47248

Aichi, Japan

Site Reference ID/Investigator# 47253

Fukuoka, Japan

Site Reference ID/Investigator# 47251

Hyogo, Japan

Site Reference ID/Investigator# 47254

Kagoshima, Japan

Site Reference ID/Investigator# 47250

Kobe, Japan

Site Reference ID/Investigator# 47255

Okinawa, Japan

Site Reference ID/Investigator# 7153

Sendai, Japan

Site Reference ID/Investigator# 47249

Takatsuki, Japan

Site Reference ID/Investigator# 47243

Tokyo, Japan

Site Reference ID/Investigator# 47244

Tokyo, Japan

Site Reference ID/Investigator# 47245

Tokyo, Japan

Site Reference ID/Investigator# 47246

Yokohama, Japan

Sponsors and Collaborators

Abbott

Eisai Co., Ltd.

Investigators

• Study Director: Shigeki Hashimoto, PhD; Abbott Japan Co.,Ltd

More Information

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

Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.

Imagawa T, Takei S, Umebayashi H, Yamaguchi K, Itoh Y, Kawai T, Iwata N, Murata T, Okafuji I, Miyoshi M, Onoe Y, Kawano Y, Kinjo N, Mori M, Mozaffarian N, Kupper H, Santra S, Patel G, Kawai S, Yokota S. Efficacy, pharmacokinetics, and safety of adalimumab in pediatric patients with juvenile idiopathic arthritis in Japan. Clin Rheumatol. 2012 Dec;31(12):1713-21. doi: 10.1007/s10067-012-2082-5. Epub 2012 Oct 2.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00690573
• Other Study ID Numbers: M10-240
• First Posted: June 4, 2008
• Results First Posted: April 1, 2011
• Last Update Posted: September 10, 2012
• Last Verified: September 2012

Keywords provided by Abbott:

Juvenile Rheumatoid Arthritis

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Arthritis, Juvenile; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Adalimumab; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents