A Study Evaluating the Efficacy and Safety of Momelotinib in Participants With Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome

NCT07569081 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2234012025-524416-11-00
• Study Type: interventional
• Target: 192
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the efficacy and safety of momelotinib in participants with a diagnosis of VEXAS.

Conditions

VEXAS Syndrome

Keywords

VEXAS Syndrome; Momelotinib; Adaptive; Ubiquitin-like modifier activating enzyme 1 mutation; ATLAS

Outcome Measures

Primary Outcomes (1)

• ORR (Objective response rate) at Week 26

  ORR is defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) during the 26-week Primary Treatment Period.

  At Week 26

Secondary Outcomes (22)

• Phase 2: Percentage of participants with partial response (PR) or complete response (CR) at Week 26

  At Week 26

• Phase 2: Number of participants with adverse events and clinically significant changes in laboratory parameters, and vital signs to support identification of the RP3D

  Up to 26 Weeks

• Phase 2: Plasma concentrations of momelotinib and metabolite of momelotinib 21 (M21) to support identification of the RP3D

  Up to 26 Weeks

• Number of flare-free days

  Up to 26 Weeks

• Duration of response (DoR)

  Up to 104 Weeks

Study Arms (3)

Momelotinib Dose level 1 + Glucocorticoids

EXPERIMENTAL

Participants will receive momelotinib at dose level 1 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3.

Drug: Momelotinib; Drug: Glucocorticoids

Momelotinib Dose level 2 + Glucocorticoids

EXPERIMENTAL

Participants will receive momelotinib at dose level 2 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3

Drug: Momelotinib; Drug: Glucocorticoids

Placebo + Glucocorticoids

PLACEBO COMPARATOR

Participants will receive momelotinib matched placebo along with glucocorticoids as a background therapy(prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3

Drug: Glucocorticoids; Drug: Placebo

Interventions

Momelotinib DRUG

Momelotinib will be administered

Also known as: GSK3070785

Momelotinib Dose level 1 + Glucocorticoids; Momelotinib Dose level 2 + Glucocorticoids

Glucocorticoids DRUG

Glucocorticoids (prednisone or prednisolone) will be administered

Momelotinib Dose level 1 + Glucocorticoids; Momelotinib Dose level 2 + Glucocorticoids; Placebo + Glucocorticoids

Placebo DRUG

Placebo will be administered

Placebo + Glucocorticoids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than equal to (\>=)18 years OR of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the Informed Consent Form.
• Confirmed diagnosis of clinical VEXAS defined by:
• Documented evidence of a canonical, pathogenic Ubiquitin-like modifier activating enzyme 1 (UBA1) mutation
• Inflammatory manifestations: current or documented past involvement within 6 months of at least one organ system
• Receiving glucocorticoid (GC) treatment (prednisone/prednisolone) for \>=4 consecutive weeks for \>=10 days prior to randomization.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
• Is a Participant of non-childbearing potential (PONCBP) OR
• Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective
• Is capable of giving signed informed consent including compliance with the requirements and restrictions
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at the time of screening.
• Has adequate organ function

You may not qualify if:

• More than 1 prior admission to an intensive care unit due to a VEXAS flare within the 6 months prior to randomization.
• History of severe corticosteroid toxicity: uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, nausea or vomiting or gastrointestinal disease.
• High risk/very high risk Myelodysplastic syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-R) with overall risk score \>3.5.
• Peripheral blood blast counts \>=10%.
• Multiple myeloma (all stages) and other active plasma cell dyscrasias requiring treatment.
• Malignancy (except disease under study including Lower-risk myelodysplastic syndrome \[LR-MDS\]) that has progressed or required active treatment within the past (24 months) except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas).
• Uncontrolled intercurrent illness within 12 weeks prior to initiation of momelotinib.
• Ongoing adverse reaction(s) from prior therapy that have not recovered to Grade \<=1 per NCI CTCAE v6.0 or to the Baseline status preceding prior therapy
• Psychiatric illness, social situation, or any other condition that would limit informed consent and/or compliance with trial requirements or may interfere with the interpretation of study results, as judged by Investigator or Sponsor.
• Has any clinically significant gastrointestinal conditions or abnormalities that may alter absorption or swallowing
• Known contraindication or hypersensitivity to momelotinib and its metabolites, or any of their excipients.
• Presence of peripheral neuropathy \>=Grade 2 per NCI CTCAE v6.0.
• Known history of disseminated mycobacterial infection.
• Known positive status for human immunodeficiency virus (HIV).
• Positive QuantiFERON (or other interferon gamma release assay) during Screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

VEXAS syndrome

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Glucocorticoids

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: May 6, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): December 6, 2028
• Study Completion (Estimated): June 4, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share