BAFF/IL-17 Bispecific Antibody Treatment in Subjects With Primary Sjogren's Syndrome (BAFF/IL-17)

To demonstrate that tibulizumab (LY3090106) treatment improves the mean unstimulated salivary flow rate or the salivary gland total ultrasound score (TUS) in primary Sjogren's syndrome patients at week 12 compared to the baseline visit.

Study Overview

• Status: Withdrawn
• Conditions: Primary Sjogren's Syndrome
• Intervention / Treatment: Drug: tibulizumab (LY3090106)

Detailed Description

This will be a single-site, open-label study in patients with primary Sjogren's syndrome. All patients will receive tibulizumab (LY3090106) 300mg subcutaneously every 2 weeks for a total of 12 weeks.

Primary Sjogren's syndrome was selected as a relevant patient population based on the mechanism of action of the molecule and the current understanding of the pathogenesis of the disease. An open-label design was chosen based on practical considerations regarding the number of patients that could be recruited. Although open-label studies are subject to bias, objective primary endpoints were intentionally chosen to minimize this concern.

The goal of this study is to demonstrate that tibulizumab (LY3090106) treatment improves the mean unstimulated salivary flow rate or the salivary gland total ultrasound score (TUS) in primary Sjogren's syndrome patients at week 12 compared to the baseline visit.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women 18-85 years of age
• Confirmed diagnosis of primary Sjogren's syndrome by the 2016 ACR-EULAR classification criteria for primary Sjogren's syndrome
• 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 unless they are not of child bearing potential
• Have stimulated whole salivary flow rate of greater than or equal to 0.10 ml/minute
• Have a salivary gland total ultrasound score (TUS) of less than or equal to 9 (on a 0-11 point scale)

Exclusion Criteria:

• Currently enrolled in a clinical trial involving an investigational product or off-label use of a drug
• Concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have received any nonbiologic investigational product within 30 days or 5 half-lives (whichever is longer) of their baseline (Day 1) visit
• Have received any biologic investigational product within 3 months or 5 half-lives (whichever is longer) of their baseline visit, or any leukocyte depleting agent within 12 months of baseline

• Have disease-modifying antirheumatic drug (DMARD) or immunosuppressive use as follows:

  • ANY treatment with a janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, upadacitinib, or filgotinib) within 28 days prior to baseline or planned treatment with a JAK inhibitor during the study
  • UNSTABLE PRESCRIBED DOSE of other synthetic DMARDs (eg, hydroxychloroquine, methotrexate, leflunomide, or sulfasalazine) within 28 days prior to baseline or if the dose of drug is planned to be increased during the study (stable prescriptions are allowed)
  • ANY treatment with cytotoxic or immunosuppressive drugs including but not limited to cyclophosphamide, mycophenolic acid, azathioprine, cyclosporine, sirolimus, or tacrolimus within 28 days prior to screening or planned treatment during the study
  • Have had treatment with biologic DMARDs as follows: Etanercept, adalimumab, or anakinra <4 weeks before baseline or planned treatment during the study
  • Have had treatment with biologic DMARDs as follows: Infliximab, certolizumab pegol, golimumab, abatacept, or tocilizumab <8 weeks before baseline or planned treatment during the study
• Are persons who have previously completed or withdrawn from this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: open label; open label study; all subjects will receive the same drug at the same dose	Drug: tibulizumab (LY3090106); subcutaneous injections of 300mg every 2 weeks over a period of 12 weeks; Other Names: open label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
whole unstimulated sialometry	change in unstimulated salivary flow	baseline
whole unstimulated sialometry	change in unstimulated salivary flow	week 12
salivary gland ultrasound	change in salivary gland ultrasound score	baseline
salivary gland ultrasound	change in salivary gland ultrasound score	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ESSDAI	change in the ESSDAI disease activity score The EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) is a physician administered questionnaire containing 12 organ-specific domains designed to measure disease activity. The ESSDAI score is obtained by addition of the twelve domain scores. Each domain score is obtained by multiplying the activity level with the domain weight. The maximum theoretical ESSDAI score is 123 and the minimum score is 0. A higher score means more disease activity (worse outcome).	baseline
ESSDAI	change in the ESSDAI disease activity score The EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) is a physician administered questionnaire containing 12 organ-specific domains designed to measure disease activity. The ESSDAI score is obtained by addition of the twelve domain scores. Each domain score is obtained by multiplying the activity level with the domain weight. The maximum theoretical ESSDAI score is 123 and the minimum score is 0. A higher score means more disease activity (worse outcome).	week 12
ESSPRI	change in the ESSPRI disease activity score The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient completed questionnaire to assess subjective patient symptoms, which includes 3 domains (dryness, fatigue, and pain). The ESSPRI score is calculated by averaging the three domains with a maximum severity score of 10 and minimum score of 0. A higher score means more disease activity (worse outcome).	baseline
ESSPRI	change in the ESSPRI disease activity score The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient completed questionnaire to assess subjective patient symptoms, which includes 3 domains (dryness, fatigue, and pain). The ESSPRI score is calculated by averaging the three domains with a maximum severity score of 10 and minimum score of 0. A higher score means more disease activity (worse outcome).	week 12
whole stimulated sialometry	change in stimulated salivary flow rate	baseline
whole stimulated sialometry	change in stimulated salivary flow rate	week 12
Schirmer I test	change in the Schirmer I test	baseline
Schirmer I test	change in the Schirmer I test	week 12
MRI	change in MRI (parenchymal architecture scored 0 to 4 and sialography scored 0 to 4)	baseline
MRI	change in MRI (parenchymal architecture scored 0 to 4 and sialography scored 0 to 4)	week 12
PET	change in PET (parotid and submandibular gland SUVmax)	baseline
PET	change in PET (parotid and submandibular gland SUVmax)	week 12

Collaborators and Investigators

• Sponsor: Matthew C. Baker

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: September 12, 2020
• First Submitted That Met QC Criteria: September 19, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: 56505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No