What is the mechanism of action of this treatment?

Janus Kinase (JAK) inhibitors, such as Upadacitinib, work by blocking the activity of enzymes in the JAK family, which are crucial in the signaling pathways that lead to inflammation. By inhibiting these enzymes, JAK inhibitors reduce the production of inflammatory cytokines, thereby decreasing inflammation and immune response. This mechanism is vital for Juvenile Idiopathic Arthritis (JIA) patients as it helps control symptoms like joint pain, swelling, and stiffness, and can prevent long-term joint damage. Other common treatments for JIA include methotrexate, which reduces cell proliferation, and biologics like TNF inhibitors, which block inflammatory pathways.

What side effects are associated with this type of intervention?

Common treatments for Juvenile Idiopathic Arthritis (JIA) include nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and biologic agents such as TNF inhibitors and JAK inhibitors like Upadacitinib. NSAIDs can cause gastrointestinal issues, renal problems, and cardiovascular effects. Methotrexate is associated with liver toxicity, bone marrow suppression, and gastrointestinal disturbances. Biologic agents, including TNF inhibitors, can increase the risk of infections, injection site reactions, and potential malignancies. JAK inhibitors, such as Upadacitinib, may cause venous thrombosis, pulmonary embolism, infections including tuberculosis, and malignancies.

What prior FDA approvals exist?

The FDA has approved several treatments for Juvenile Idiopathic Arthritis (JIA), including biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). Similar to Upadacitinib, Tofacitinib is another JAK inhibitor that has been approved for JIA. Additionally, biologic agents such as Etanercept, Adalimumab, and Abatacept have been approved for treating various forms of JIA. These treatments aim to reduce inflammation and improve symptoms in children with JIA.

What other types of research exist?

Promising alternatives to Upadacitinib for JIA patients include: 1) Abatacept, a T-cell modulator, which has shown efficacy in clinical trials for JIA. 2) Methotrexate in combination with prednisone, which has demonstrated improved outcomes compared to prednisone alone. 3) Biologic agents such as Etanercept and Adalimumab, which are TNF inhibitors with established efficacy in pediatric rheumatology. 4) Ustekinumab, an IL-12/23 inhibitor, which has shown positive results in psoriatic arthritis and may be considered for JIA.

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Janus Kinase (JAK) Inhibitor

Upadacitinib for Juvenile Arthritis (SELECT-YOUTH Trial)

Phase 1

Waitlist Available

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant have total body weight of 10 kg or higher at the time of screening.

If receiving methotrexate (MTX), have been taking MTX for at least 12 weeks immediately before and including Study Day 1 on a stable dose of 10 to 20 mg/m2 for at least 8 weeks before and including Study Day 1; in addition, participants should take either folic acid or folinic acid according to local standard of care.

Must not have

Participant have prior exposure to JAK inhibitor.

Participant with diagnosis of enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (JPSA).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 156 weeks

Awards & highlights

Summary

This trial is testing a medication called upadacitinib in children with a type of arthritis that affects many joints. The study aims to see how the drug behaves in their bodies, how safe it is, and how well they can tolerate it. Upadacitinib works by reducing inflammation and pain by blocking certain enzymes in the body. It has been approved for treating rheumatoid arthritis in adults.

Who is the study for?

This trial is for children with polyarticular course juvenile idiopathic arthritis (pcJIA) who have at least 5 active joints and weigh over 10 kg. They must have been diagnosed with pcJIA, possibly taking methotrexate for 12 weeks or more, and if on steroids, they should be on a stable dose. Kids with enthesitis-related arthritis or juvenile psoriatic arthritis, or those previously treated with JAK inhibitors can't participate.

What is being tested?

The study tests Upadacitinib's effects in kids with pcJIA across three parts: initial multiple-dose groups, an open-label extension to assess long-term safety/tolerability, and an additional cohort for further safety evaluation. The goal is to understand how the drug works in young bodies and monitor its ongoing safety.

What are the potential side effects?

While specific side effects are not listed here, typically such trials look out for any adverse reactions related to the medication being tested which could include gastrointestinal issues, skin reactions, changes in blood counts or liver enzymes among others.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I weigh at least 10 kg.

Select...

I have been on a stable dose of methotrexate for at least 8 weeks and take folic or folinic acid.

Select...

I have 5 or more joints with swelling, pain, or limited movement.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with a JAK inhibitor before.

Select...

I have been diagnosed with ERA or JPSA.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 156 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 156 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 156 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Apparent oral clearance at steady state (CL/F)

Part 1: Area under plasma concentration versus time curve during a dosing interval (AUCtau)

Part 1: Half-life

+3 more

Side effects data

From 2023 Phase 3 trial • 657 Patients • NCT03086343

24%

COVID-19

15%

URINARY TRACT INFECTION

14%

NASOPHARYNGITIS

11%

UPPER RESPIRATORY TRACT INFECTION

10%

RHEUMATOID ARTHRITIS

HYPERTENSION

HERPES ZOSTER

BACK PAIN

ALANINE AMINOTRANSFERASE INCREASED

NAUSEA

BRONCHITIS

ASPARTATE AMINOTRANSFERASE INCREASED

COUGH

BLOOD CREATINE PHOSPHOKINASE INCREASED

ARTHRALGIA

WEIGHT INCREASED

HYPERCHOLESTEROLAEMIA

HEADACHE

INFLUENZA

OSTEOARTHRITIS

FALL

DEPRESSION

ANAEMIA

NEUTROPENIA

COVID-19 PNEUMONIA

EAR INFECTION

SPINAL OSTEOARTHRITIS

VITAMIN D DEFICIENCY

CYSTITIS

RESPIRATORY TRACT INFECTION

PHARYNGITIS

SINUSITIS

GREATER TROCHANTERIC PAIN SYNDROME

DIARRHOEA

VOMITING

FATIGUE

PYREXIA

HEPATIC STEATOSIS

GASTROENTERITIS

ANXIETY

GASTRITIS

LATENT TUBERCULOSIS

PNEUMONIA

INSOMNIA

SCIATICA

DYSPEPSIA

MITRAL VALVE INCOMPETENCE

DERMATITIS ALLERGIC

HIP FRACTURE

IRON DEFICIENCY ANAEMIA

BLOOD PRESSURE INCREASED

CARPAL TUNNEL SYNDROME

PULMONARY MASS

PRURITUS

CATARACT

ABDOMINAL PAIN

MUSCULOSKELETAL CHEST PAIN

PARAESTHESIA

SYNCOPE

SEPTIC SHOCK

PULMONARY EMBOLISM

TOOTH INFECTION

TOOTH FRACTURE

PHARYNGITIS STREPTOCOCCAL

VIRAL UPPER RESPIRATORY TRACT INFECTION

ATRIAL FIBRILLATION

PLEURAL EFFUSION

TACHYCARDIA

TINNITUS

PERIPHERAL SWELLING

ASYMPTOMATIC COVID-19

HERPES SIMPLEX

PERIODONTITIS

CONTUSION

BLOOD CREATININE INCREASED

BLOOD TRIGLYCERIDES INCREASED

HAEMOGLOBIN DECREASED

HEPATIC ENZYME INCREASED

LIVER FUNCTION TEST INCREASED

OSTEOPENIA

DIZZINESS

RENAL CYST

DYSPHONIA

NASAL CONGESTION

RHINORRHOEA

COSTOCHONDRITIS

MUSCLE SPASMS

OSTEOPOROSIS

ASTHMA

DEVICE DISLOCATION

TRICUSPID VALVE INCOMPETENCE

GLAUCOMA

CONSTIPATION

CHOLELITHIASIS

LOCALISED INFECTION

ONYCHOMYCOSIS

ORAL CANDIDIASIS

DECREASED APPETITE

DIABETES MELLITUS

100%

80%

60%

40%

20%

Study treatment Arm

Period 2, Primary Cohort: Upadacitinib 15 mg QD/Upadacitinib 15 mg QD

Period 2, 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD/Upadacitinib 15 mg QD

Period 1, 30 mg Cohort: Upadacitinib 30 mg QD

Period 2, 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD

Period 2, Primary Cohort: Abatacept/Upadacitinib 15 mg QD

Period 2, 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD

Period 2, 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD/Upadacitinib 15 mg QD

Period 1, Primary and 30 mg Cohorts: Abatacept

Period 1, Primary Cohort: Upadacitinib 15 mg QD

Trial Design

5Treatment groups

Experimental Treatment

Group I: Participants of age group 6 to <12 years receiving dose AExperimental Treatment1 Intervention

Participants of age group 6 to \<12 years administered with upadacitinib dose A (weight dependent) as described in the protocol.

Group II: Participants of age group 2 to <6 years receiving dose AExperimental Treatment1 Intervention

Participants of age group 2 to \<6 years administered with upadacitinib dose A (weight dependent) as described in the protocol.

Group III: Participants of age group 2 to <18 years receiving dose AExperimental Treatment1 Intervention

Participants of age group 2 to \<18 years administered with upadacitinib dose A as described in the protocol.

Group IV: Participants of age group 12 to <18 years receiving dose BExperimental Treatment1 Intervention

Participants of age group 12 to \<18 years administered with upadacitinib dose B (weight dependent) as described in the protocol.

Group V: Participants of age group 12 to <18 years receiving dose AExperimental Treatment1 Intervention

Participants of age group 12 to \<18 years administered with upadacitinib dose A (weight dependent) as described in the protocol.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Upadacitinib

2014

Completed Phase 3

~9710

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Janus Kinase (JAK) inhibitors, such as Upadacitinib, work by blocking the activity of enzymes in the JAK family, which are crucial in the signaling pathways that lead to inflammation. By inhibiting these enzymes, JAK inhibitors reduce the production of inflammatory cytokines, thereby decreasing inflammation and immune response. This mechanism is vital for Juvenile Idiopathic Arthritis (JIA) patients as it helps control symptoms like joint pain, swelling, and stiffness, and can prevent long-term joint damage. Other common treatments for JIA include methotrexate, which reduces cell proliferation, and biologics like TNF inhibitors, which block inflammatory pathways.