Upacitinib in Treatment of JAK/STAT Pathway Disorders With Activating Mutations

Conditions

• JAK1 GOF
• STAT1 GOF
• STAT3 GOF
• STAT5B GOF
• STAT6 GOF

Eligibility Criteria

Sex

ALL

Age

12 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• Upadacitinib — DRUG
  Participants will receive the dose that worked best for them (optimal treatment dose, OTD) during the earlier open-label phase of the study, which may be 15 mg, 30 mg, or 45 mg taken once daily. The study drug will be taken by mouth as tablets.
• Placebo — DRUG
  Participants assigned to the placebo group will receive placebo tablets taken once daily. The placebo will be matched to the participant's optimal treatment dose (OTD) determined during the earlier open-label phase of the study.

Study Details

This study focuses on a genetic condition that affects the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) immune signaling pathway. A specific change in the DNA leads to overactivation of this pathway, which can result in immune dysregulation and related clinical symptoms. Currently, five genetic mutations are known to cause these JAK-STAT pathway driven immune disorders: STAT1, STAT3, STAT5B, STAT6, and JAK1 (collectively referred to as JAK-STAT disorders). This study is a basket clinical trial, meaning patients with these different but related genetic conditions are enrolled in the same study and treated with the same investigational therapy. The purpose of this study is to evaluate the safety and tolerability (ability to tolerate) of a drug called Upadacitinib in patients with JAK-STAT disorders with activating mutations. This drug belongs to a class of drug called Janus kinase (JAK) inhibitors, also known as JAKinibs. It is a type of immune system modulating medication that regulates (fixes) the JAK- STAT signaling pathway. Upadacitinib has been approved by the FDA for multiple immunological diseases and disorders. Presently, there is no FDA approved treatment for this group of JAK-STAT disorders. The study will also investigate immune factors in the blood to develop diagnosis methods that can be used in the future for better medical management of these disorders. The study consists of four phases: screening phase, open label phase, randomized withdrawal phase and maintenance phase. The study will last approximately 12 months. While in the study, participants will receive a once daily dose of Upadacitinib that best helps control their disease. During the study participants will be asked to answer questions about their health and medical history. They will also complete physical exams, blood tests, and other questionnaires.

Key Dates

Start date

Aug 31, 2026

Status verified

Jun 2026

Primary completion

Aug 31, 2028

Completion

Aug 31, 2028

Study Design

Enrollment

30 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Upadacitinib (Drug)
  During the 8-week randomized withdrawal (RW) phase, participants in this arm will receive upadacitinib at the dose that was determined to work best for them (optimal treatment dose, OTD) during the earlier open-label phase of the study (15 mg, 30 mg, or 45 mg OTD). This study is not designed to compare the different dose levels. Therefore, participants receiving any of the three dose levels will be considered as one arm because each participant is receiving their own OTD.
• Placebo Comparator: Matching Placebo
  During the 8-week RW phase, participants assigned to receive placebo will receive placebo tablets that match their OTD selected during the earlier phase of the study.

Primary Outcome Measure

Treatment Efficacy - TIme to first occurrence of disease reactivation [ Time Frame: During the 8 weeks of the randomized withdrawal phase ]

Central Contacts

• Supriya Parikh
  8328242589
  [email protected]
• Sik Yu So
  8328241318
  [email protected]

Locations (3)

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