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

Summary

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.

Conditions

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

Interventions

DRUG

Upadacitinib

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.

DRUG

Placebo

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.

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• AbbVie

  collaborator INDUSTRY

• Lisa Satter

  lead OTHER

Principal Investigators

• Lisa F Satter, MD · Baylor College of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

12 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-31

Primary Completion

2028-08-31

Completion

2028-08-31

FDA Drug

Yes

Countries

• United States

Study Locations