Trial Outcomes & Findings for Safety, Efficacy, and Pharmacokinetics of Adalimumab in Japanese Children With Juvenile Rheumatoid Arthritis (NCT NCT00690573)

Last Updated: 2012-09-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

Week 16

Results posted on

2012-09-10

Participant Flow

Adalimumab dose was determined by baseline body weight (20 mg for subjects weighing \< 30 kg, 40 mg for subjects weighing 30 kg or more) through Week 14. After Week 16, dose was based on body weight measured at Week 16 and every 12 weeks. Twenty subjects received concomitant methotrexate therapy during the study.

Participant milestones

Participant milestones
Measure	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).
Overall Study STARTED	25
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	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).
Overall Study Lack of Efficacy	8
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab n=25 Participants 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).
Age, Categorical <=18 years	25 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	13.0 years STANDARD_DEVIATION 3.38 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment Japan	25 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 16

Population: The analysis was conducted using the full analysis set (FAS) population, which was defined as all subjects who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Adalimumab n=25 Participants 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).
Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16	23 Participants

SECONDARY outcome

Timeframe: Week 16

Population: The analysis was conducted using the full analysis set (FAS) population, which was defined as all subjects who received at least one dose of study drug. Missing values were treated as non-responders.

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=25 Participants 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).
Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 Number of Subjects Achieving PedACR50 at Week 16	22 Participants
Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 Number of Subjects Achieving PedACR70 at Week 16	15 Participants

SECONDARY outcome

Timeframe: 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

Population: The analysis was conducted using the full analysis set (FAS) population (all subjects who received at least 1 dose of study drug) as observed. N=25 at Weeks 2, 4, and the Final Visit; N=24 at Weeks 8, 24, and 36; N=23 at Week 48; N=22 at Week 60; N=19 at Weeks 72 and 96; N=11 at Week 120; and N=5 at Week 144.

Outcome measures

Outcome measures
Measure	Adalimumab n=25 Participants 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).
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 36	22 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 48	21 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 60	20 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 72	19 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 96	18 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 120	11 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 144	5 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30- Final Visit	22 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 2	7 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 4	13 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 8	15 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 24	19 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 36	22 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 48	19 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 60	20 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 72	18 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 96	18 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 120	11 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50 at Week 144	5 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR50- Final Visit	20 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 2	1 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 2	15 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 4	16 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 8	19 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR30 at Week 24	21 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 4	7 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 8	8 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 24	15 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 36	19 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 48	17 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 60	16 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 72	15 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 96	14 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 120	11 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70 at Week 144	5 Participants
Number of Subjects Achieving PedACR 30/50/70 Responses Number of subjects achieving PedACR70- Final Visit	17 Participants

SECONDARY outcome

Timeframe: Week 2, 4, 8, 16, and 24, and every 12 weeks up to Week 60

Population: For the 20 mg dose, N = 8 at each timepoint. For the 40 mg dose, N = 17 at Weeks 2 and 4; N = 16 at Weeks 8, 16, and 24; N = 14 at Week 36; N = 15 at Week 48; and N = 14 at 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).

Outcome measures

Outcome measures
Measure	Adalimumab n=25 Participants 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).
Mean Serum Adalimumab Concentration 20 mg dose at Week 2	5.24 mcg/mL Standard Deviation 1.74
Mean Serum Adalimumab Concentration 20 mg dose at Week 4	5.46 mcg/mL Standard Deviation 5.18
Mean Serum Adalimumab Concentration 20 mg dose at Week 8	6.15 mcg/mL Standard Deviation 5.88
Mean Serum Adalimumab Concentration 20 mg dose at Week 16	5.73 mcg/mL Standard Deviation 5.26
Mean Serum Adalimumab Concentration 20 mg dose at Week 24	5.79 mcg/mL Standard Deviation 6.51
Mean Serum Adalimumab Concentration 20 mg dose at Week 36	7.60 mcg/mL Standard Deviation 7.58
Mean Serum Adalimumab Concentration 20 mg dose at Week 48	7.97 mcg/mL Standard Deviation 6.69
Mean Serum Adalimumab Concentration 20 mg dose at Week 60	11.4 mcg/mL Standard Deviation 9.87
Mean Serum Adalimumab Concentration 40 mg dose at Week 2	5.03 mcg/mL Standard Deviation 1.45
Mean Serum Adalimumab Concentration 40 mg dose at Week 4	5.63 mcg/mL Standard Deviation 2.71
Mean Serum Adalimumab Concentration 40 mg dose at Week 8	8.66 mcg/mL Standard Deviation 4.41
Mean Serum Adalimumab Concentration 40 mg dose at Week 16	10.8 mcg/mL Standard Deviation 6.15
Mean Serum Adalimumab Concentration 40 mg dose at Week 24	11.9 mcg/mL Standard Deviation 6.80
Mean Serum Adalimumab Concentration 40 mg dose at Week 36	12.6 mcg/mL Standard Deviation 6.44
Mean Serum Adalimumab Concentration 40 mg dose at Week 48	13.0 mcg/mL Standard Deviation 8.89
Mean Serum Adalimumab Concentration 40 mg dose at Week 60	13.1 mcg/mL Standard Deviation 6.73

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adalimumab n=25 Participants 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).
Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) Number of subjects with AAA by Week 24	4 Participants
Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) Number of subjects with AAA by Week 60	6 Participants

Adverse Events

Adalimumab

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adalimumab n=25 participants at risk 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).
General disorders pyrexia	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations hepatitis B	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations herpes zoster	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations pharyngitis	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations pneumonia	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Metabolism and nutrition disorders dehydration	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Musculoskeletal and connective tissue disorders arthralgia	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Musculoskeletal and connective tissue disorders juvenile arthritis	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Nervous system disorders amnesia	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	4.0% 1/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.

Other adverse events

Other adverse events
Measure	Adalimumab n=25 participants at risk 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).
Blood and lymphatic system disorders iron deficiency anaemia	20.0% 5/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Eye disorders conjunctivitis	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Eye disorders conjunctivitis allergic	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Eye disorders keratoconjunctivitis sicca	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders abdominal pain	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders abdominal pain upper	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders constipation	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders dental caries	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders diarrhoea	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders nausea	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders stomatitis	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Gastrointestinal disorders vomiting	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
General disorders injection site erythema	16.0% 4/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
General disorders injection site reaction	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
General disorders malaise	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
General disorders pyrexia	20.0% 5/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Hepatobiliary disorders hepatic function abnormal	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Immune system disorders seasonal allergy	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations gastroenteritis	24.0% 6/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations hordeolum	20.0% 5/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations impetigo	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations influenza	32.0% 8/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations nasopharyngitis	56.0% 14/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations oral herpes	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations pharyngitis	32.0% 8/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Infections and infestations upper respiratory tract infection	56.0% 14/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Injury, poisoning and procedural complications contusion	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Injury, poisoning and procedural complications hand fracture	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Injury, poisoning and procedural complications joint sprain	16.0% 4/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Investigations antinuclear antibody positive	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Investigations DNA antibody positive	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Musculoskeletal and connective tissue disorders arthralgia	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Musculoskeletal and connective tissue disorders juvenile arthritis	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Musculoskeletal and connective tissue disorders myalgia	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Nervous system disorders headache	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Respiratory, thoracic and mediastinal disorders cough	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	16.0% 4/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Respiratory, thoracic and mediastinal disorders rhinitis allergic	12.0% 3/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Respiratory, thoracic and mediastinal disorders rhinorrhoea	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders acne	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders dermatitis atopic	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders dermatitis bullous	8.0% 2/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders eczema	20.0% 5/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders rash	16.0% 4/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Skin and subcutaneous tissue disorders urticaria	24.0% 6/25 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.

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