A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 12 Weeks in Adults With Active Primary Sjögren's Syndrome (pSS)

NCT04700280 | Terminated Phase 2 Results DMC

• 2 other identifiers: GLPG3970-CL-2072020-003298-22
• Study Type: interventional
• Target: 31
• Locations: 5 countries
• Sites: 10

Brief Summary

This is a first exploration of GLPG3970 in participants with active primary Sjogren's Syndrome (pSS) to evaluate the efficacy, safety and tolerability and to determine its pharmacokinetics (PK) profile compared to placebo.

Conditions

Primary Sjögren Syndrome

Keywords

Primary Sjögren Syndrome; Sjögren Syndrome; Autoimmune Diseases; Rheumatic Diseases; Sicca Syndrome

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) Score at Week 12

  The ESSDAI is a systemic disease activity index to assess 12 domains (organ systems: constitutional, lymphadenopathy and lymphoma, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, CNS, hematological, biological) in participants with pSS. Each of the domains was assessed for activity level (no, low, moderate, and high). Each domain score was obtained by multiplying the activity level with the domain weight, ranged from 1 to 6, and assigned a numerical score based on pre-determined weighting of each individual domain. The sum of all individual weighted domain scores was the overall score, ranged from 0 (best) to 123 (worst activity). A higher score indicated more disease activity. A clinically meaningful reduction from baseline (≥3 points) indicated the improvement of symptoms. Least squares (LS) mean was calculated using mixed models for repeated measures (MMRM).

  Baseline, Week 12

• Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) by Severity

  An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) current version at the time of assessment. The maximum intensity of the AE were Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). A TEAE was any AE with an onset date on or after the first dose of GLPG3970 and no later than 30 days after last dose of GLPG3970, or any worsening of any AE on or after the GLPG3970 start date.

  From first dose of study drug up to 30 days after last dose of study drug (maximum duration=16 weeks)

Secondary Outcomes (3)

• Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Score at Weeks 4, 8, and 12

  Baseline, Weeks 4, 8, and 12

• Change From Baseline in ESSDAI Score at Weeks 4, 8, and 12

  Baseline, Weeks 4, 8, and 12

• Observed Pre-dose Plasma Concentration (Ctrough) of GLPG3970

  Pre-dose (within 30 minutes prior to dosing) on Weeks 1, 4, 8, and 12

Study Arms (2)

GLPG3970

EXPERIMENTAL

Participants will receive GLPG3970 400 milligrams (mg) (2 \*200 mg tablet), orally, once daily for 12 weeks.

Drug: GLPG3970

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to GLPG3970 tablet, orally, once daily for 12 weeks.

Drug: Placebo

Interventions

GLPG3970 DRUG

GLPG3970 film-coated tablet.

GLPG3970

Placebo DRUG

Placebo film-coated tablet.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of pSS for \<10 years prior to screening AND defined by the classification criteria \>=4 described by the American College of Rheumatology - European League Against Rheumatism (ACR-EULAR).
• Participant has an ESSDAI score \>=5 assessed on 7 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, hematological, and biological.
• Participant has an ESSPRI score \>=5.
• Participant has stimulated whole salivary flow rate of \>=0.1 milliliter per minute (mL/min).
• Participant has positive serum titers of anti-Sjögren's-syndrome-related antigen A (anti-SS-A)/Ro and/or anti-SS-B/La antibodies.
• Participants already on treatment should be on stable standard of care (SoC) for at least 4 weeks prior to first investigational product (IP) dosing.
• The following SoC medications are permitted:
• Corticosteroids \<=7.5 mg/day (prednisone or equivalent); AND/OR
• Non-steroidal anti-inflammatory drugs (NSAIDs); AND/OR
• One single antimalarial at a stable dose (hydroxychloroquine \<=400 mg/day; quinacrine 100 mg/kg/day, or chloroquine \<=250 mg/day); AND/OR
• One single immunosuppressant at a stable dose (methotrexate \[MTX\] \<=10 mg/week or azathioprine \[AZA\] \<=2 mg/kg/day); AND/OR
• One single cholinergic stimulant at a stable dose (e.g., pilocarpine, cevimeline).
• Female participant of childbearing potential must have a negative highly sensitive (serum beta human chorionic gonadotropin or urine dipstick) pregnancy test.
• Female participant of childbearing potential or male participant must agree to use highly effective contraception/preventive exposure measures.

You may not qualify if:

• Secondary Sjögren's syndrome according to the ACR-EULAR (2016) classification.
• History or presence of unstable condition not related to Sjögren's Syndrome that, in the opinion of the investigator, could constitute an unacceptable risk when taking the IP or interfere with the interpretation of data.
• Participant has any active systemic infection within 2 weeks prior to first IP dosing, or poorly controlled chronic cardiac, pulmonary, or renal disease.
• Participant has a known or suspected history of or a current immunosuppressive condition, or a history of opportunistic infections (e.g., human immunodeficiency virus \[HIV\] infection, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis).
• Participant has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV surface antigen (HBsAg) positivity. Participant has hepatitis C virus (HCV) infection, as defined by positive HCV antibody at screening and detectable HCV viremia. Participants with positive HCV antibody must undergo reflex HCV ribonucleic acid (RNA) testing, and participants with HCV RNA positivity will be excluded. Participants with positive HCV antibody and negative HCV RNA are eligible.
• Participant testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as detected at screening based on real time polymerase chain reaction (RT-PCR) or at baseline based on immunoglobulin M (IgM) immunoassay, or participants who have been in contact with SARS-CoV-2 infected individuals in the 2 weeks prior to first dosing of IP. Participants presenting any signs or symptoms of SARS-CoV-2 infection, as detected prior to first IP dosing following careful physical examination (e.g., cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc). In addition, any other locally applicable standard diagnostic criteria may also apply to rule out SARS-CoV-2 infection.
• Participant has taken any disallowed therapies:
• Mycophenolate mofetil (MMF) within a week prior to screening.
• Cyclosporine/Tacrolimus within a week prior to screening.
• Cyclophosphamide within 6 months prior to screening.
• Ocular medicines (e.g., topical cyclosporine, topical NSAIDs/ corticosteroids) for at least 4 weeks prior to screening, except for a sporadic use.
• Biologics such as, but not limited to, rituximab, abatacept, and any other unapproved biologic within 6 months prior to screening.
• Plasmapheresis within 12 weeks prior to screening.
• Plasma exchange within 12 weeks prior to screening.
• Intravenous immunoglobulin (IVIG) therapy within 24 weeks prior to screening.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (10)

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

General Hospital of Athens Laiko

Athens, 11527, Greece

Location

Debreceni Egyetem

Debrecen, 4032, Hungary

Location

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-363, Poland

Location

ETG Lublin

Lublin, 20-412, Poland

Location

Centrum Badan Klinicznych S.C.

Poznan, 60-773, Poland

Location

Medycyna Kliniczna

Warsaw, 00-874, Poland

Location

NZOZ Centrum Medyczne Reuma Park

Warsaw, 02-691, Poland

Location

Medical Center Harmoniya Krasy

Kyiv, 1135, Ukraine

Location

MeSH Terms

Conditions

Sjogren's Syndrome; Autoimmune Diseases; Rheumatic Diseases

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Limitations and Caveats

There were limitations in the dataset, given the small number of participants completing the treatment period due to early termination of the study.

Results Point of Contact

• Title: Galapagos Medical Information
• Organization: Galapagos NV

medicalinfo@glpg.com

+32 15 342 900

Study Officials

• Catherine Vincent

  Galapagos NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: January 6, 2021
• First Posted: January 7, 2021
• Study Start: January 28, 2021
• Primary Completion: October 28, 2021
• Study Completion: December 27, 2021
• Last Updated: September 18, 2023
• Results First Posted: September 18, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); PL (6); GR (1); UA (1); DE (1)