Primary Sjogren's SyndromePhase 2NCT05781451

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

A Phase 2 study testing LY3361237 in people with Primary Sjogren's Syndrome, run by Stanford University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Primary Sjogren's Syndrome
What is being tested?: LY3361237
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 1 Jan 2025to 1 Jan 2028
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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]

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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

Who cannot join

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

About this study

Official title: A Phase 2, Open Label Study of Anti-BTLA Agonist Therapy in Subjects 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.

Read the detailed description

This study is a single-site, open-label study in subjects with primary Sjogren's syndrome being conducted at the Stanford University rheumatology clinic. All eligible subjects will receive LY3361237 450mg SC Q2W over a period of 12 weeks and will be followed up for an additional 10 weeks after the last dose. Twelve subjects will be included in the study.

After the Screening visit, consenting patients will be seen in clinic on day 1 (Baseline) and return to clinic on Weeks 2, 4, 6, 8, 10, 12, and 22.

At Screening (up to 35 days before baseline), a complete medical history, physical exam, vital signs, clinical laboratory tests [comprehensive metabolic panel, complete blood count, quantitative immunoglobulins, ANA, RF, anti-Ro, anti-La, C3, C4, ESR, CRP, urinalysis, urine protein:creatinine, serum pregnancy test for females, HIV serologies, hepatitis B serologies, hepatitis C serologies, quantiFERON test for tuberculosis, SARS-CoV-2 PCR], chest x-ray, electrocardiogram, and salivary gland ultrasound will be conducted.

At all subsequent visits, at a minimum, a complete physical exam, vital signs, focused history, and clinical laboratory tests (comprehensive metabolic panel, complete blood count, ESR, CRP, and urine pregnancy test for females) will be conducted.

Efficacy will be assessed using the Sjogren's Tool for Assessing Response (STAR) and by measuring changes in unstimulated salivary flow rate, changes in salivary glands by ultrasound, changes in salivary glands by PET/MRI, changes in Schirmer I testing, changes in laboratory values including inflammatory markers (ESR, CRP) complement levels (C3, C4), immunoglobulins (IgG, IgA, IgM), and autoantibodies (ANA, SS-A, SS-B, RF), and changes in patient reported outcomes.

At Screening, Baseline, Week 4, and Week 12, patients will record their global assessment of disease as well as visual analog scales for ocular and salivary symptoms and the ESSPRI. At Baseline, Week 4, and Week 12, patients will record the FACIT-F for fatigue and RAND SF-36, and the physician will calculate the ESSDAI, ClinESSDAI, physician global assessment of disease, and tender and swollen joint count.

In addition, safety will be assessed for all patients.

Conditions: Primary Sjogren's Syndrome
Being tested: LY3361237

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LY3361237Drug
Also called Venanprubart
All patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks.

Study groups in NCT05781451
Study group	Role	What they receive
LY3361237	Experimental	All patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks. Receives: Drug: LY3361237

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 12

Secondary outcomes (6)

Change in unstimulated salivary flow
Unstimulated salivary flow as assessed by sialometry.
Measured: Baseline and Week 12
Change in salivary gland ultrasound score
The Hočevar salivary gland ultrasound score (SGUS) will be calculated by assessing Parenchymal echogeneity, Homogeneity, Presence of hypoechogenic areas, Hyperechogenic reflections, and Clearness of salivary gland borders. The Hočevar ultrasound score will be calculated by summation of the grades for the five parameters described above for all four glands, with a range of 0-48 (with a higher score reflecting worse disease activity).
Measured: Baseline and Week 12
Change in MRI findings on PET/MRI imaging
Imaging of the head and neck will be performed using positron emission magnetic resonance imaging. MRI of the salivary glands in Sjogren's syndrome patient demonstrate inhomogeneity of the parenchyma on both T1- and T2-weighted sequences.
Measured: Baseline and Week 12
Change in FDG uptake on PET/MRI imaging
Imaging of the head and neck will be performed using positron emission magnetic resonance imaging. FDG-PET may demonstrate areas of uptake signaling active inflammation.
Measured: Baseline and Week 12
Change in EULAR Sjögren's syndrome (SS) disease activity index
The ESSDAI is a systemic disease activity index that was designed to measure disease activity in patients with primary Sjogren's syndrome.
The ESSDAI consists of a composite numerical score of 12 organ specific "domains" contributing to disease activity (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system, muscular, hematological, and biological parameters). Each domain is divided into 3 to 4 levels according to the degree of activity and scored as 0 (no activity), 1 (low activity), 2 (moderate activity), or 3 (high activity). These scores are then multiplied by an assigned weight factor, ranging from 1 to 6, with the total score ranging from 0 to 123 points. A higher score denotes more disease activity.
Measured: Baseline and Week 12
Change in Schirmer I test
Schirmer's test is used to determine whether the eye produces enough tears to keep it moist.
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 20251 Jan 2028

First posted23 Mar 2023
Study start1 Jan 2025 (estimated)
Primary completion1 Jan 2027 (estimated)
Study completion1 Jan 2028 (estimated)

Why it stopped: Drug unavailable

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Primary Sjogren's SyndromeStudies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05781451
Sponsor's protocol ID: 68283
Status last verified: Apr 2024
First submitted: 23 Feb 2023
Last updated: 17 Apr 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Primary Sjogren's Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open Label Study of Anti-BTLA Agonist Therapy in Subjects With Primary Sjogren's Syndrome
ClinicalTrials.gov ID: NCT05781451
Acronym / sponsor ID: 68283
Conditions: Primary Sjogren's Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Drug unavailable
Enrolment: 0 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Study start: 1 Jan 2025 (estimated)
Primary completion: 1 Jan 2027 (estimated)
Study completion: 1 Jan 2028 (estimated)
First posted: 23 Mar 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The secondary objective is to determine the effect of LY3361237 on glandular changes measured by PET/MRI.

Detailed description

After the Screening visit, consenting patients will be seen in clinic on day 1 (Baseline) and return to clinic on Weeks 2, 4, 6, 8, 10, 12, and 22.

In addition, safety will be assessed for all patients.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LY3361237	Experimental	Drug: LY3361237All patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LY3361237Also: VenanprubartAll patients will receive LY3361237 450mg subcutaneously every 2 weeks for a total of 12 weeks.	Drug	LY3361237

Primary outcome

Change in the Sjogren's Tool for Assessing Response (STAR)
Time frame: Baseline and Week 12
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.

6 secondary outcomes

Change in unstimulated salivary flow
Time frame: Baseline and Week 12
Change in salivary gland ultrasound score
Time frame: Baseline and Week 12
Change in MRI findings on PET/MRI imaging
Time frame: Baseline and Week 12
Change in FDG uptake on PET/MRI imaging
Time frame: Baseline and Week 12
Change in EULAR Sjögren's syndrome (SS) disease activity index
Time frame: Baseline and Week 12
Change in Schirmer I test
Time frame: Baseline and Week 12

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
Individual participant dataSharing planned: No

Related trials for Primary Sjogren's Syndrome

Recruiting
Evaluation of the Prevalence, and Immunological Characteristics of Small Fiber Neuropathy in Patients With Primary Sjögren's Syndrome
Sjögren's Syndrome, Small Fiber Neuropathy
Not yet recruiting
MYTP01 for Immune-Mediated Diseases
IgA Nephropathy, Kidney Transplant Recipients
RecruitingPhase 2
Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren Disease
Sjogren's Syndrome
Not yet recruitingPhase 1
A Phase 1 Study of QLS2416 Injection in Participants With Autoimmune Diseases
Systemic Lupus Erythematosus, Rheumatoid Arthritis (RA)
RecruitingPhase 3
Phase 3 Study of Telitacicept in Active Primary Sjögren's Disease
Primary Sjogren's Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Matthew C Baker, MD, MS principal investigator

Stanford University

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LY3361237 in people with Primary Sjogren's Syndrome, run by Stanford University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Sjogren's Tool for Assessing Response (STAR) (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05781451.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.