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

Teijin

Status and phase: Completed; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: TCK-276; Drug: TCK-276 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05437419

TCK-276-102

Details and patient eligibility

About

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).

Full description

This is a Phase 1, multi-center, double-blind, randomized, placebo-controlled, multiple ascending dose (MAD) study.

The study will consist of a Screening Visit (Days -1 to Day 10), Treatment duration (up to 11 days) and a Follow-up/end of treatment (EOT) visit.

This MAD study will consist of 4 cohorts of 8 patients (6 active treatment and 2 matching placebo, or a 3:1 ratio), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily (QD) under fed condition). The first cohort will be divided into 2 subgroups to implement the sentinel dosing approach.

The study duration is approximately 42 days.

Enrollment: 32 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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 sequelae 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 Severe Acute Respiratory Syndrome Corona Virus 2 (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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32 participants in 4 patient groups

Cohort 1

Experimental group

Description:

The patient will receive Dose A of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Treatment:

Drug: TCK-276 Placebo

Drug: TCK-276

Cohort 2

Experimental group

Description:

The patient will receive Dose B of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Treatment:

Drug: TCK-276 Placebo

Drug: TCK-276

Cohort 3

Experimental group

Description:

The patient will receive Dose C of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Treatment:

Drug: TCK-276 Placebo

Drug: TCK-276

Cohort 4

Experimental group

Description:

The patient will receive Dose D of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Treatment:

Drug: TCK-276 Placebo

Drug: TCK-276