An Open-label Study of GC012F in Rheumatoid Arthritis.

NCT07315503 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: IIT2025116
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is An Open-label Study to Evaluate the Safety and Efficacy of GC012F in Patients with Difficult-to-Treat (D2T) Rheumatoid Arthritis.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis;CAR-T cell therapy

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT) Rate

  DLT is defined as an AE that occurs within 28 days of GC012F CAR-T product reinfusion.DLT will be evaluated according to NCI-CTCAE V5.0 criteria.

  28 days

• Adverse Events （AEs）、Serious (SAE)、Adverse Event of Special Interest(AESI) Rate

  Proportion of subjects experiencing AE within 15 years after infusion of GC012F CAR-T cell injection.

  Up to 15 years from treatment discontinuation

Secondary Outcomes (13)

• GC012F T cell count in peripheral blood (Pharmacokinetic evaluation indicators)

  Up to 15 years from treatment discontinuation

• GC012F CAR gene copy number in peripheral blood (Pharmacodynamic evaluation indicators,)

  Up to 15 years from treatment discontinuation

• Changes in the concentration of soluble B-cell maturation antigen (BCMA) in peripheral blood

  Up to 15 years from treatment discontinuation

• Quantification of cytokines Changes in peripheral blood

  Up to 15 years from treatment discontinuation

• Quantification of immunoglobulins (Ig) Changes in peripheral blood

  Up to 15 years from treatment discontinuation

Study Arms (2)

LD and GC012F CAR-T Cell Injection

EXPERIMENTAL

The first 6 subjects will be randomized in a 1:1 ratio after apheresis to the LD cohort or the LD-free cohort，in the LD cohort subject will receiving GC012F infusion following lymphodepletion,For the subsequent 3 patients, whether to perform pretreatment and the dosage of the study drug will be determined after evaluating the first 6 patients.

GC012F CAR-T Cell Injection

EXPERIMENTAL

The first 6 subjects will be randomized in a 1:1 ratio after apheresis to the LD cohort or the LD-free cohort，in the LD-free cohort the subject will directly receiving GC012F infusion without lymphodepletion,For the subsequent 3 patients, whether to perform pretreatment and the dosage of the study drug will be determined after evaluating the first 6 patients.

Drug: GC012F CAR-T Cell Injection

Interventions

LD and GC012F CAR-T Cell Injection DRUG

Subjects will receive cyclophosphamide 200 to 300 mg/m2 and fludarabine 20 to 30 mg/m2 once daily for 3 days either on Days -5, -4 and -3 or on Days -4, -3 and -2 prior to CAR-T cell infusion.

Also known as: cyclophosphamide, fludarabine

GC012F CAR-T Cell Injection DRUG

the LD-free cohort ，directly receiving GC012F infusion without lymphodepletion.

GC012F CAR-T Cell Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Capable of signing the informed consent form and willing and able to comply with study procedures;
• \) Age ≥ 18 years (or the local legal age of consent in the region where the study is conducted) and ≤ 75 years at the time of signing the informed consent form;
• \) Women of childbearing potential (WOCBP) (women who have undergone hysterectomy or have been postmenopausal for at least 2 years are not considered to be of childbearing potential) must:
• a) Have a negative serum or urine beta-human chorionic gonadotropin (β-hCG) pregnancy test result as confirmed by the investigator during screening, as the study drug may pose potential risks or unknown effects to the fetus;
• b) Agree to avoid breastfeeding during the study and for at least 2 years after GC012F infusion, or until CAR-T cells become undetectable by two consecutive assessments using flow cytometry (whichever occurs later);
• \) Male subjects with female partners of childbearing potential and female subjects of childbearing potential must agree to use effective contraceptive methods (such as oral contraceptives, intrauterine devices, or condoms) from the start of screening and for at least 2 years following GC012F infusion, or until CAR-T cells become undetectable by two consecutive assessments using flow cytometry (whichever occurs later); Male subjects must agree to use condoms during sexual activity with pregnant women or women of childbearing potential for at least 2 years following GC012F infusion, even if they have undergone successful vasectomy;
• \) Able to establish venous access required for apheresis, with no contraindications to apheresis.
• \) Laboratory test results during screening must meet the following criteria (excluding criteria specific to the disease under study):
• Organ and bone marrow function:
• Absolute neutrophil count ≥ 1.0 × 109/L (no growth factor support within 7 days prior to laboratory tests);
• Absolute lymphocyte count ≥ 0.5 × 109/L;
• Hemoglobin ≥ 80 g/L (no pre-transfusion of red blood cells within 7 days prior to laboratory tests);
• Platelet count ≥ 50 × 109/L (no pre-transfusion within 7 days prior to laboratory tests);
• Serum immunoglobulin G (IgG) ≥ 500 mg/dL;
• Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN;

You may not qualify if:

• \) Receipt of any other investigational drug within 4 weeks prior to signing the ICF, or the ICF signing date falls within 5 half-lives after the last dose of the investigational drug during subjects' recent participation in a clinical study (whichever is longer);
• \) Uncontrolled and/or infection requiring hospitalization or intravenous antimicrobial therapy (fungal, bacterial, viral, or other infections) within 4 weeks prior to screening. Subjects with simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis who respond to the current therapy may be enrolled;
• \) Active tuberculosis or inadequately treated latent tuberculosis prior to or during screening;
• \) History of severe hypersensitivity or allergy;
• \) History of severe immediate allergic reaction to any drug used in this study, including GC012F and its excipients (including dimethyl sulfoxide), fludarabine and cyclophosphamide (applicable only to subjects who plan to receive lymphodepletion), tocilizumab, or any component of the study drug, or presence of any contraindication, life-threatening allergy, hypersensitivity, or intolerance to these agents;
• \) Those who have inflammatory bowel disease requiring treatment or any clinically significant gastrointestinal disease within the past 5 years;
• \) Primary immunodeficiency;
• \) Cardiac insufficiency or clinically significant cardiac disease, including:
• a) New York Heart Association (NYHA) functional class III or IV congestive heart failure within 6 months prior to enrollment;
• c) Clinically significant arrhythmias (such as ventricular tachycardia, patients with atrial fibrillation/flutter with well-controlled ventricular rate \[average heart rate at rest\< 100 bpm\] may be eligible at the investigator's discretion), QTc interval corrected by Fredericia formula \> 450 ms in males or \> 470 ms in females, complete left bundle branch block, high-degree atrioventricular (AV) block, or unexplained syncope at screening not attributable to vasovagal response or dehydration;
• d) Non-ischemic dilated cardiomyopathy, hypertrophic cardiomyopathy, cardiac amyloidosis, or sarcoidosis, clinically significant aortic valve stenosis, or severe aortic/mitral valve incompetence;
• e) History of severe non-ischemic cardiomyopathy;
• f) Uncontrolled hypertension.
• \) History of severe respiratory disease or active severe respiratory disease, including moderate or more severe asthma or chronic obstructive pulmonary disease (COPD), interstitial lung disease, or pulmonary fibrosis;
• \) Presence of or history of liver cirrhosis;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, China

Tianjin, China

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Ying Wang

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Wang

CONTACT

15900225626; wangying@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study plans to enroll a total of 9 evaluable subjects; GC012F will be administered at the starting dose of 2 × 10\^5 CAR-T cells/kg. The first 6 subjects will be randomized in a 1:1 ratio after apheresis to the LD cohort (receiving GC012F infusion following lymphodepletion) or the LD-free cohort (directly receiving GC012F infusion without lymphodepletion). After the DLT observation period, i.e., a minimum of 28 days of following GC012F infusion, is completed for all 6 subjects, all available data (including PK, PD, safety, efficacy, and biomarker data) obtained from the treatment period will be reviewed to determine the conditioning regimen and dose for subsequent evaluation.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 2, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2041
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

CN (1)