CLN-978 injections for people with moderate to severe Sjögren's disease

A Phase 1b, Open-Label Study of CLN-978 for the Treatment of Active, Moderate to Severe Sjogren's Disease

This trial will try subcutaneous injections of CLN-978, a CD19-directed T cell engager, in adults with active moderate-to-severe Sjögren's disease to see if it reduces disease activity.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cullinan Therapeutics Inc. (industry)
• Locations: 11 sites (Orlando, Florida and 10 other locations)
• Trial ID: NCT07041099 on ClinicalTrials.gov

What this trial studies

This open-label phase 1b study gives subcutaneous doses of CLN-978, a CD19-directed T cell engager, to adults with active moderate-to-severe Sjögren's disease to characterize safety, tolerability, pharmacokinetics, and early signs of clinical effect. Eligible participants must have a diagnosis meeting the 2016 EULAR/ACR criteria, at least 24 weeks since diagnosis, an ESSDAI score of 5 or greater, and meet specific laboratory thresholds including peripheral CD19+ B cell counts. Key exclusions include concomitant other rheumatologic autoimmune diseases, high thrombotic risk, rapidly progressive glomerulonephritis or heavy proteinuria, and active severe central nervous system manifestations. Dosing and follow-up visits are conducted at Cullinan investigative sites in the United States.

Who should consider this trial

Good fit: Adults diagnosed with Sjögren's disease for at least 24 weeks who meet the 2016 EULAR/ACR criteria, have active moderate-to-severe disease (ESSDAI ≥5), and meet the listed laboratory thresholds are the target participants.

Not a fit: Patients with other concomitant rheumatologic autoimmune diseases, high thrombotic risk, very low B cell counts, severe renal impairment (eGFR <30 mL/min/1.73 m2), or active severe CNS manifestations are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, CLN-978 could reduce B cell activity and improve systemic symptoms in people with moderate-to-severe Sjögren's disease.

How similar studies have performed: B cell–targeted therapies such as anti-CD20 antibodies have produced mixed results in Sjögren's, and CD19-directed T cell engagers are a newer approach with limited clinical data in autoimmune disease.

Eligibility criteria

Inclusion

* Diagnosis of SjD at least 24 weeks prior to Screening Visit and meet the 2016 EULAR / ACR Classification Criteria for SjD at Screening.
* Have active moderate to severe disease (i.e., ESSDAI ≥5) at Screening.
* Laboratory parameters including the following:

  * Absolute lymphocyte count (ALC) ≥0.5 × 10\^9/L
  * Peripheral CD19+ B cell count ≥25 cells/µL
  * Absolute neutrophil count (ANC) ≥1.0 × 10\^9/L
  * Hemoglobin (Hgb) ≥8 g/dL
  * Platelet count ≥75 × 10\^9/L
  * Total bilirubin ≤1.5 × ULN, except patients with confirmed Gilbert's Syndrome
  * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.0 × ULN
  * Estimated glomerular filtration rate (eGFR) based on the CKD-EPI formula ≥30 mL/min/1.73 m2

Exclusion

* Concomitant rheumatological autoimmune disease
* Considered at high risk for thrombosis
* Rapidly progressive glomerulonephritis and/or urine protein/creatinine \>3 mg/mg (339 mg/mmol).
* Active, severe central nervous system manifestations of SjD.
* History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder that the Investigator feels would put the patient at undue risk or confound study results.
* Evidence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), or cytomegalovirus (CMV) infection.
* Primary immunodeficiency or history of recurrent infections.
* History of splenectomy.
* Live or attenuated vaccine within 28 days prior to the Screening Visit or during the Screening Period.
* Active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, within 14 days prior to Day 1.
* Active or latent tuberculosis (TB)

Where this trial is running

Orlando, Florida and 10 other locations

• Cullinan Investigative Site — Orlando, Florida, United States (RECRUITING)
• Cullinan Investigative Site — Memphis, Tennessee, United States (RECRUITING)
• Cullinan Investigative Site — Plano, Texas, United States (RECRUITING)
• Cullinan Investigative Site — Webster, Texas, United States (RECRUITING)
• Cullinan Investigative Site — Salt Lake City, Utah, United States (RECRUITING)
• Cullinan Investigative Site — Brest, France (RECRUITING)
• Cullinan Investigative Site — Le Kremlin-Bicêtre, France (RECRUITING)
• Cullinan Investigative Site — Strasbourg, France (RECRUITING)
• Cullinan Investigative Site — Erlangen, Germany (RECRUITING)
• Cullinan Investigative Site — Hanover, Germany (RECRUITING)
• Cullinan Investigative Site — Roma, Italy (RECRUITING)

Study contacts

• Study coordinator: Amy Gubits, MPH

Conditions: Sjögren, Sjogren Disease, Sjogren's Syndrome, CLN-978