Upadacitinib for JAK/STAT Pathway Disorders with Activating Mutations

This study is testing Upadacitinib, a medication, for people aged 12 to 65 who have specific genetic conditions called JAK/STAT pathway disorders. These conditions are caused by an overactive immune signaling pathway due to certain genetic changes (mutations) in genes like JAK1, STAT1, STAT3, STAT5B, or STAT6. The study aims to see how well Upadacitinib works to prevent disease flare-ups and to track any side effects. Participants will receive either Upadacitinib or a placebo (an inactive substance) daily by mouth. To join, you must have a confirmed JAK/STAT mutation and show signs of immune dysregulation. The study plans to enroll 30 participants, but its current status is unclear.

Study design
This is a multi-center trial with an initial open-label phase where all participants receive Upadacitinib, followed by a double-blind, placebo-controlled phase. It plans to enroll 30 participants.
What's involved
Participants will take Upadacitinib or placebo tablets once daily. During the initial phase, you will have site visits and remote monitoring (phone calls and blood tests) to adjust your dose.
Compensation
Not stated in the trial record.
Follow-up
The study will track side effects and organ toxicity throughout the entire treatment period, which is 1 year.

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NCT07670156

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

Not Yet Recruiting
PHASE1Ages 12–65InterventionalTreatment
Lisa Satter
~30 participants
Updated 2026-07-02 on ClinicalTrials.gov
What's tested:UpadacitinibPlacebo

At a glance

Recruiting sites
0 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Treatment Efficacy - TIme to first occurrence of disease reactivation
Measured over During the 8 weeks of the randomized withdrawal phase
+2 more outcomes measured
JAK1 GOF
STAT1 GOF
STAT3 GOF
STAT5B GOF
STAT6 GOF
3 sites across 3 states
Missouri1
New York1
Texas1
  • Lisa F Satter, MD · STUDY_CHAIR · Baylor College of Medicine

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Eligibility criteria

Inclusion

At least 30kg
Patients with a confirmed JAK/STATGOF mutation with evidence of immune dysregulation
Current disease status meeting criteria as defined in the disease scoring module
Expected survival of more than 12 months
Willingness to allow storage of biological samples for future research
Agreement to use highly effective contraception (for female participants)

Exclusion

Hypersensitivity to the study drug or any medication in the same class
Active infections
Central nervous system (CNS) manifestations
Pregnancy
Medical conditions or use of concomitant medications that may interfere with the effect or evaluation of the study drug
Laboratory abnormalities as specified in the protocol
Receipt of a live vaccine within 30 days prior to study treatment
High risk or history of osteoporosis, thrombosis, gastrointestinal (GI) perforation, or malignancy
  • Treatment Efficacy - TIme to first occurrence of disease reactivationDuring the 8 weeks of the randomized withdrawal phase

    All patients that complete the open label dose-escalation phase and are randomized will be included in the efficacy analysis population. Efficacy of the Optimal Tolerated Dose (OTD) will be assessed by comparing the time to first occurrence of disease reactivation using Primary Immune Regulatory Deficiency (PIRD) score during the 8-week Randomized Withdrawal (RW) phase between the Upadacitinib and placebo groups. The PIRD score is a disease scoring method that capture the clinical manifestations of all PIRDs including JAK/STAT GOF disorders. The presence of a disease state and its severity is graded on a scale of 1-5. 1 indicates the absence of the disease. Disease flare is defined as an increase in PIRD score by ≥1 in disease manifestations.

  • Safety and Tolerability - Percentage of Patients with Adverse Events of Special InterestThroughout the whole treatment period (1 year)

    All patients that receive at least one dose of study drug will be included in the analyses to evaluate safety and tolerability of the study drug. Safety and tolerability will be summarized for each phase of the study and will be assessed primarily based on adverse events of special interest. Assessment of safety and tolerability will primarily be done by calculating the percentage of patients with adverse events of special interest.

  • Safety and Tolerability - Percentage of Patients with Organ ToxicityThroughout the whole treatment period (1 year)

    All patients that receive at least one dose of study drug will be included in the analyses to evaluate safety and tolerability of the study drug. Safety and tolerability will be summarized for each phase of the study and will be assessed based on organ toxicity. Organ toxicity will be assessed by clinical labs. Assessment of safety and tolerability will primarily be done by calculating the percentage of patients with organ specific toxicities.