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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 October 2024
• Main ID: NCT05437419
• Date of registration: 23/06/2022
• Prospective Registration: Yes
• Primary sponsor: Teijin America, Inc.
• Public title: A Study to Investigate Safety, Tolerability, and PK of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis
• Scientific title: A Phase 1, Randomized, Placebo-controlled, Double-blind, Multiple Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis
• Date of first enrolment: August 10, 2022
• Target sample size: 32
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT05437419
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Tatyana Zubkovskaya
• Affiliation: Medical Director

Key inclusion & exclusion 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 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.


Age minimum: 18 Years
Age maximum: 64 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: TCK-276 Placebo

Drug: TCK-276

Primary Outcome(s)

Number ot Participants With Treatment Emergent Adverse Events [Time Frame: 42 days (duration of study)]

Secondary Outcome(s)

t½: Terminal Elimination Half-life [Time Frame: Day 1 and Day 7]

Vz/F: Apparent Volume of Distribution Based on Terminal Phase (Parent Only) [Time Frame: Day 1 and Day 7]

Fe 0-24: Percentage of Study Drug Excreted Unchanged in the Urine (Days 1 and 7) [Time Frame: Day 1 and Day 7]

Fe 0-72: Percentage of Study Drug Excreted Unchanged in the Urine [Time Frame: Day 7 0-72 hours]

MRT0-inf: Mean Residence Time Extrapolated to Infinity [Time Frame: Day 1 and Day 7]

Racc (Cmax): Accumulation Ratio Based on Cmax [Time Frame: Day 1 and Day 7]

Ae 0-24: Amount of Study Drug Excreted Unchanged in the Urine (Days 1 and 7) [Time Frame: Day 1 and Day 7]

MR for Area Under the Plasma Concentration-time Curve (AUC)0-inf [Time Frame: Day 1 and Day 7]

AUC0-inf: Area Under the Plasma Concentration Time Curve From Pre-dose (Time 0) Extrapolated to Infinite Time [Time Frame: Day 1 and Day 7]

Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 (Metabolite) [Time Frame: Day 1 and Day 7]

Racc (AUCtau): Accumulation Ratio Based on AUCtau [Time Frame: Day 1 and Day 7]

MR for Area Under the Plasma Concentration-time Curve (AUC)Tau [Time Frame: Day 1 and Day 7]

Ae 0-72: Amount of Study Drug Excreted Unchanged in the Urine (Day 7) [Time Frame: Day 7 0-72 hours]

Metabolic Ratio (MR) for Cmax [Time Frame: Day 1 and Day 7]

Clearance Renal (CLr): Renal Clearance (Days 1 and 7) [Time Frame: Day 1 and Day 7]

AUCtau: Area Under the Plasma Concentration-time Curve Over a Dosing Interval, Tau = 24 Hours [Time Frame: Day 1 and Day 7]

Clearance (CL)/F: Apparent Total Body Clearance (Parent Only) [Time Frame: Day 1 and Day 7]

Tmax: Time of Maximum Plasma Concentration Determined Directly From the Concentration-time Profile [Time Frame: Day 1 and Day 7]

Secondary ID(s)

TCK-276-102

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Parexel

Results

• Results available: Yes
• Date Posted: 15/10/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT05437419