A Study of CLN-978, a Subcutaneously Administered CD19-directed T Cell Engager, in Subjects With Rheumatoid Arthritis

Phase 1

Recruiting

• Conditions: Rheumatoid Arthritis (RA
• Interventions: Drug: CLN-978

• Registration Number: NCT06994143
• Lead Sponsor: Cullinan Therapeutics Inc.

Brief Summary

A Phase I, open-label study of CLN-978 in patients with treatment-refractory rheumatoid arthritis.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-05-19
• Study First Submitted: 2025-05-20
• Study First Submitted QC: 2025-05-20
• Study First Posted: 2025-05-29
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-06
• Last Update Posted: 2025-06-11
• Primary Completion: 2027-12-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• Documented diagnosis of RA which fulfills the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria ≥12 weeks prior to screening.

• Evidence of B-cell-driven disease at Screening or previous medical documentation, defined as either (i) seropositivity for RF and/or any AMPA and/or (ii) a synovial biopsy showing B-cell infiltration

• Active RA disease, as demonstrated by a DAS28 - ESR ≥3.2 and at least one swollen joint at screening.

• Inadequate response to at least 2 targeted treatments with different mechanisms. These can include tsDMARD and/or bDMARD, after failing conventional synthetic DMARD (unless contraindicated).

• Local laboratory assessments must meet the following criteria:

  • Absolute lymphocyte count (ALC) ≥0.5 x 10^9/L
  • Peripheral CD19+ B cell count ≥25 cells/μL
  • Absolute neutrophil count (ANC) ≥1.0 x 10^9/L
  • Hemoglobin (Hgb) ≥8 g/dL
  • Platelet count ≥75 x 10^9/L
  • Estimated glomerular filtration rate (eGFR) (based on the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥30 mL/min/1.73m^2
  • Total bilirubin ≤1.5 × ULN, except patients with confirmed Gilbert's Syndrome
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN

• Concurrent corticosteroids is permitted if the dose is ≤10 mg/day prednisone equivalent in the 2 weeks prior to initiation of study treatment. Hydroxychloroquine ≤400 mg/d or chloroquine ≤ 250 mg/d is allowed.

Exclusion Criteria

• Active inflammatory disease other than RA within 12 months prior to screening or during screening that may interfere with the study assessments. Thyroiditis or secondary Sjogren's syndrome is allowed.

• Clinical evidence of any other significant unstable or uncontrolled acute or chronic disease not due to RA which, in the opinion of the Investigator could put the patient at undue risk or confound study results.

• Prior treatment with the following:

  • Cellular therapy (e.g., chimeric antigen receptor T-cell (CAR-T) or gene therapy product directed at any target.
  • Receipt of an investigational therapy within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to Day 1 and during the study.
  • Received any anti-CD19 or anti-CD20 therapy such as blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab within 3 months prior to Day 1.
  • Non-biologic DMARD within 14 days prior to Day 1.
  • Cyclophosphamide or a biologic immunomodulating therapy within 2 months of Day 1.

• Live or live-attenuated vaccines within the 4 weeks prior to the Screening visit or during the Screening Period

• Active or latent tuberculosis (TB) evidenced by a positive or indeterminant Interferon Gamma Release Assay (IGRA), unless the patient has documented previous completion of TB treatment and no current clinical indication of TB.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Dose Escalation	CLN-978	Patients with RA treated with CLN-978 in dose escalation cohorts
Part B Further Dose Evaluation	CLN-978	Further evaluation of CLN-978 treatment of patients with RA

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events	48 wks	Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs)

Secondary Outcome Measures

Name	Time	Method
Serum concentrations of CLN-978	12 wks	Serum concentrations of CLN-978
Level of anti-drug antibodies	12 wks	Level of anti-drug antibodies
Pharmacodynamics-related biomarker	48 wks	Levels of total B lymphocytes in the peripheral blood

Trial Locations

Locations (1)

Cullinan Investigative Site; 🇩🇪 Erlangen, Germany