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Upadacitinib in Treatment of JAK/STAT Pathway Disorders With Activating Mutations (SAFE-JAKi)

1 luglio 2026 aggiornato da: Lisa Satter

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

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This is a phase 1/2, multi-center trial with an open label dose-escalation phase (OL) followed by a double-blind placebo-controlled randomized withdrawal phase (RW) to study the safety, tolerability, and preliminary efficacy of Upadacitinib in patients with confirmed and symptomatic gain of function mutations in the JAK-STAT pathway. Upon completion of the randomized withdrawal phase, each patient will enter the maintenance phase (MP) where all patients will receive Upadacitinib.

OL Phase (16 weeks): The subject will be escalated two times if tolerated and clinically indicated based upon disease response. The starting dose will be 15 mg per day for patients greater than or equal to 12 years of age (and at least 30 kg in weight). The subject will remain at this dose level for 28 days. The subject will visit the clinical site on day 1 of each dose escalation visit and then will be remotely monitored (phone call and laboratory monitoring to check complete blood counts) on Day 3 and Day 10.

Patients must have a disease status score of 2 or higher utilizing the Primary Immune Regulatory Deficiency (PIRD) Disease Modules prior to initiation of dose-escalation of the drug. The PIRD score is a disease scoring method that capture the clinical manifestations of all PIRDs including JAK/STAT GOF disorders. The PIRD scores for clinical improvement across organ systems for each patient will standardize the ability to quantify improvement across divergent disease phenotypes and assess outcomes based on clinical improvement within each disorder. Patients who demonstrate a response to study treatment, as determined by improvement in PIRD score, may proceed to the RW Phase. Patients who do not meet eligibility criteria for the RW Phase will enter MP.

During the OL Phase, the optimal treatment dose (OTD) for each patient will be determined. OTD will be defined as the dose that achieved complete response or partial response based on the PIRD scores.

RW Phase (8 weeks): For the double-blind randomized withdrawal phase, patients will be randomized to receive either the Optimum tolerated dose (OTD) dose from the OL phase or Placebo using a 1:1 randomization ratio. Subject will come to the study site every 4 weeks. The subject can discontinue the RW phase if he/she experiences a flare (worsening of disease symptoms) and will enter the Maintenance Phase outlined below. For measuring disease flare Primary Immune Regulatory Disorders (PIRD) score will be used. It will be deemed a flare if the score increases by ≥1 in disease manifestation. During the RW-phase, the reference for a disease flare (for the primary endpoint assessment) will be the end of the OL phase PIRD score.

MP Phase (28 weeks): Subject will be monitored closely for any drug related toxicities (blood counts, lipid and metabolic panels) and continue to take the highest tolerated dose level attained during the escalation phase. The subject will return to the clinical site on day 168, day 217, day 266, day 315 and day 364. Upon conclusion of the maintenance phase at day 364 the study team will safely transition the subject to clinically viable treatment alternatives that are commercially available (after a 3 days washout period for Upadacitinib).

Tipo di studio

Interventistico

Iscrizione (Stimato)

30

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Stati Uniti
    • Missouri
      • St Louis, Missouri, Stati Uniti, 63110
        • Washington University in St.Louis
        • Contatto:
        • Investigatore principale:
          • Megan Cooper, MD, PhD
    • New York
      • New York, New York, Stati Uniti, 10032
        • Columbia University
        • Investigatore principale:
          • Joseph Oved, MD
        • Contatto:
    • Texas
      • Houston, Texas, Stati Uniti, 77030
        • Baylor College of Medicine
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Lisa Satter, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Bambino
  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • 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 Criteria:

  • 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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: 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.
Droga: 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.
Altri nomi:
  • Rinvoq
Comparatore placebo: 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.
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Treatment Efficacy - TIme to first occurrence of disease reactivation
Lasso di tempo: During 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.
During the 8 weeks of the randomized withdrawal phase
Safety and Tolerability - Percentage of Patients with Adverse Events of Special Interest
Lasso di tempo: Throughout 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.
Throughout the whole treatment period (1 year)
Safety and Tolerability - Percentage of Patients with Organ Toxicity
Lasso di tempo: Throughout 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.
Throughout the whole treatment period (1 year)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in Quality of life during treatment- adults
Lasso di tempo: During the 16 weeks of OL Phase and 28 weeks of MP

Quality of life (QOL) will be assessed using validated age-adjusted tools (SF-36 for adults) at screening, beginning of the Randomized Withdrawal (RW) phase, beginning of the Maintenance Phase (MP), end of the MP.

The SF-36 (36-Item Short Form Health Survey) is an open-source patient-reported questionnaire to measure quality of life (QoL) across multiple health domains. It contains 36 items grouped into eight scales, each assessing a different aspect of health.

To assess the change in quality of life during the Open-Label (OL) phase, change from screening values will be calculated using assessments at the beginning of the RW phase. To assess the change in quality of life during the MP, the change in the QOL scores from beginning of the MP to the end of the MP will be calculated.
During the 16 weeks of OL Phase and 28 weeks of MP
Change in Quality of life during treatment- children
Lasso di tempo: During the 16 weeks of OL Phase and 28 weeks of MP

Quality of life (QOL) in children will be assessed using validated age-adjusted tools (Peds-QL for children) at screening, beginning of the Randomized Withdrawal (RW) phase, beginning of the Maintenance Phase (MP), end of the MP.

The PedsQL Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents. It uses age-appropriate questionnaires to assess physical, emotional, social, and school functioning from the child's and/or parent's perspective. Its modular design allows it to be adapted for various conditions, making it widely used in clinical research and healthcare settings.

To assess the change in quality of life during the Open-Label (OL) phase, change from screening values will be calculated using assessments at the beginning of the RW phase. To assess the change in quality of life during the MP, the change in the QOL scores from beginning of the MP to the end of the MP will be calculated.
During the 16 weeks of OL Phase and 28 weeks of MP

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Lisa Satter

Collaboratori

AbbVie
National Center for Advancing Translational Sciences (NCATS)

Investigatori

  • Cattedra di studio: Lisa F Satter, MD, Baylor College of Medicine

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 agosto 2026

Completamento primario (Stimato)

1 agosto 2028

Completamento dello studio (Stimato)

1 agosto 2028

Date di iscrizione allo studio

Primo inviato

19 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

19 giugno 2026

Primo Inserito (Effettivo)

26 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 luglio 2026

Ultimo verificato

1 luglio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • H-52366
  • 4UH3TR003908 (Sovvenzione/contratto NIH degli Stati Uniti)

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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