A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis

• Status: Not yet recruiting
• Trial end date: 2023-01-18
• Target enrollment: 0
• Participant gender: All

Summary

The study is to evaluate the safety, tolerability, and pharmacokinetic (PK) of multiple orally administered TCK-276 in both males and females with Rheumatoid Arthritis (RA).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Teijin America, Inc.
• Collaborator: Parexel

Criteria

Inclusion Criteria:

• Diagnosis of RA and meeting the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA.

• Patients between the ages of 18 and 64 years, inclusive, at the Screening Visit.

• Female patient must be not pregnant, not breast feeding and one of the following conditions need to apply:

1. Of non-childbearing potential based on documented surgical treatment or post-menopausal, meaning patient had spontaneous amenorrhea for at least 12 months without alternate medical cause prior to Screening Visit and follicle stimulating hormone (FSH) > 40 U/mL at the Screening Visit.

2. Of childbearing potential and using a highly effective method of contraception and agrees to remain on a highly effective method from the time of signing the informed consent form (ICF) until 21 days after the last dose.

• Male patient must agree to stay abstinent or must use together with his female partner(s) a form of highly effective contraceptive (failure rate of < 1% per year) from the time of signing the ICF until up to 3 months after the last dose of the study drug.

• Nonsmokers (or other nicotine use) as determined by history and by negative urine cotinine concentration at the Screening Visit and at Admission.

• Body mass index (BMI) between 18.5 and 32.0 kg/m2, inclusive, at the Screening Visit.

• Patient is required to have completed a COVID-19 vaccine regimen within no more than 5 months prior to screening to be eligible for the study.

• Permitted concomitant medications for any reason, must be on a stable dose.

• Permitted medications include: anti-malarials; nonsteroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors at approved dosage, and low dose oral corticosteroids; methotrexate concomitantly with folic acid or folinic acid.

Exclusion Criteria:

• Female patients who are breastfeeding or have a positive urine pregnancy test.

• Patients who are unable to eat the prescribed meals during the stay at the site; vegetarian or vegan.

• Patient has a history of significant drug allergy.

• Patient has used a study drug, any prohibited medication(s), over-the-counter (OTC) medications, vitamins, dietary and herbal supplements.

• Patient has a history of active suicidal ideation, or any psychiatric disorders that will affect the patient's ability to participate in the study.

• Patient has a current or recent history of uncontrolled, clinically significant infectious, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.

• Patient with any of the laboratory abnormalities as per reference.

• Patient has a history of alcohol and/or drug abuse within 24 weeks.

• Patient has positive results for drug testing and breath alcohol test.

• Regular consumption of alcohol within 6 months prior to the Screening Visit.

• Patient has positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) antibody at Screening Visit.

• Patient has QT interval corrected for heart rate (QTc) using Fridericia's correction (QTcF) > 450 ms for males or QTcF > 470 ms for females either at the Screening Visit or Admission, based on safety 12-lead electrocardiogram (ECG). Patient has Screening or Admission ECG with second- or third-degree atrioventricular block, bundle branch block, arrhythmia (but not sinus arrhythmia or supraventricular premature beats), or illegible QT interval.

• Patient has history or evidence of cardiopathy, acute coronary syndrome, hypertrophic cardiomyopathy, myocarditis or QT prolongation syndrome.

• Patient is unwilling to abstain from drinks and foods containing alcohol, grapefruit, or caffeine

• Patient has donated blood or experienced acute blood loss (including plasmapheresis) of greater than 500 mL within 90 days prior to the first dose of study drug.

• Patients with a known immunodeficiency disorder. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.

• Patients with infections requiring treatment or hospitalization within 14 days prior to the Screening Visit, parenteral antimicrobial therapy within 60 days prior to the Screening Visit, infected joint prosthesis; history of herpes zoster, active herpes simplex, or herpes simplex on suppressive therapy.

• Patient has a chronic hepatic disease or hepatic impairment.

• Patient has a history of Mycobacterium tuberculosis or positive interferon gamma release assay for tuberculosis (IGRA-TB) or abnormal chest X-ray (for positive IGRA-TB patients).

• Patient has a history of any lymphoproliferative disorder.

• Patient has a history of COVID-19 unless fully recovered with no sequalae for 14 days.

• Patient who had a severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated).

• Patient who has recent exposure to someone who has COVID-19 symptoms or positive test result.

• Patient who has a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2.

• Patient who has clinical signs and symptoms consistent with SARS-CoV-2 infection.

• Patients may not receive any live/attenuated vaccine from 30 days prior to the Screening Visit until Day 14 Follow-up Visit.

• COVID-19 vaccine should not be given 1 week prior to the Screening Visit.

• Patients with malignancy or history of malignancy except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Previous treatment with total lymphoid irradiation.

• History of recurrent inflammatory joint disease other than RA or history of any other autoimmune rheumatic diseases other than Sjogren's syndrome.

• Major surgery within 30 days prior to the Screening Visit or patients with planned surgery.

• Patients who have an abnormal chest X-ray for interstitial lung disease (ILD) and/or patients with history of ILD.

• History of fainting or family history of sudden death.

• Patient has any disorder that would interfere with the absorption, distribution, metabolism or excretion of study drug.

• Patient has a history of deep vein thrombosis and/or pulmonary embolism.

• Patient has poor venous access.