Anti-BTLA Agonist Therapy in Subjects With Primary Sjogren's Syndrome

NCT05781451 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 68283
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This will be a single-site, open-label study in patients with primary Sjogren's syndrome. The aim of this clinical trial is to evaluate the safety and efficacy of anti-BTLA agonist therapy (LY3361237) in treating patients with primary Sjogren's syndrome. The primary objective is to evaluate the efficacy of LY3361237 in patients with primary Sjogren's syndrome by assessing changes in the Sjogren's Tool for Assessing Response (STAR) after 12 weeks of treatment. The secondary objective is to determine the effect of LY3361237 on glandular changes measured by PET/MRI.

Conditions

Primary Sjogren's Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in the Sjogren's Tool for Assessing Response (STAR)

  Change from Baseline to Week 12 after treatment with LY3361237. STAR is intended to assess treatment efficacy based on improvement of disease activity for primary Sjögren's syndrome. The STAR contains 5 domains: systemic activity, symptoms, lacrimal and glandular gland function, and biomarkers of auto-immune activity. The score consists of five domains (systemic activity worth 3 points, patient-reported outcome worth 3 points, lacrimal gland function worth 1 point, salivary gland function worth 1 point, and biological worth 1 point). A patient is considered a STAR responder if they accrue ≥5 points.

  Baseline and Week 12

Secondary Outcomes (6)

• Change in unstimulated salivary flow

  Baseline and Week 12

• Change in salivary gland ultrasound score

  Baseline and Week 12

• Change in MRI findings on PET/MRI imaging

  Baseline and Week 12

• Change in FDG uptake on PET/MRI imaging

  Baseline and Week 12

• Change in EULAR Sjögren's syndrome (SS) disease activity index

  Baseline and Week 12

Study Arms (1)

LY3361237

EXPERIMENTAL

All patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks.

Drug: LY3361237

Interventions

LY3361237 DRUG

All patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks.

Also known as: Venanprubart

LY3361237

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are eligible for enrollment in the study only if they meet all of the following criteria:
• Have given written informed consent
• Are men or women aged 18 to 85, inclusive, at the time of initial screening
• Have a confirmed diagnosis of primary Sjogren's syndrome by the 2016 ACR-EULAR classification criteria for primary Sjogren's syndrome \[2\]
• ≥50mm on a visual analog scale (VAS) for ocular dryness or oral dryness or ≥5 on the ESSPRI score for dryness
• Have a Hočevar salivary gland ultrasound score (SGUS) (on a 0-48 point scale) and ≥10 \[to detect relatively early disease with less anatomic derangement that will potentially be more responsive to treatment and to exclude patients with no changes on ultrasound that would preclude an ability to see improvement\] \[3\]
• All women (regardless of childbearing potential) must test negative for pregnancy at the time of screening. Women must also agree to use a reliable method of birth control from screening until 12 weeks following last dose of study drug (adequate contraceptive measures include: intrauterine devices, hormonal contraceptives, complete sexual abstinence, or vasectomized partner), unless they are not of child-bearing potential as defined by meeting either of the following:
• Are at least 6 weeks after bilateral oophorectomy, tubal ligation, or hysterectomy
• Are postmenopausal, as defined by having had spontaneous amenorrhea for at least 12 months and a follicle-stimulating hormone level \>40 mIU/mL at screening
• Have venous access sufficient to allow for blood sampling, as per the protocol
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

You may not qualify if:

• Prior treatment with a BTLA agonist within 6 months before baseline
• Use of other biologic agents including TNF inhibitors, abatacept, IL-6 inhibitors, or BAFF inhibitors within 8 weeks prior to baseline
• Use of a B cell depleting therapy (such as rituximab) within 12 months prior to baseline
• A history of, or current, inflammatory or autoimmune disease (that could affect the interpretation of safety or efficacy outcomes) other than primary Sjogren's syndrome
• Evidence of active tuberculosis, HIV, or hepatitis B or C infection
• Have a diagnosis or history of malignant disease within 5 years prior to baseline, with the following exceptions: basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years and/or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline
• Prior LASIK or radial keratotomy surgery which could affect symptomatic complaints of eye dryness

Sponsors & Collaborators

• Stanford University: lead

Study Officials

• Matthew C Baker, MD, MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Chief and Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 23, 2023
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share