Evaluation of K9 in Subjects With Thyroid Eye Disease (TED)

Thyroid Eye Disease Clinical Trial

Official title:

Evaluation of K9 in Subjects With Thyroid Eye Disease (TED)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06467435
• Other study ID #: 94519
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: May 2025

Study information

• Verified date: June 2024
• Source: University of Kentucky
• Contact: Connie Dampier
• Phone: 859-562-0750
• Email: dampier[@]email.uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this clinical trial is to evaluate the plasma pharmacokinetics of K9 in healthy subjects (Cohort 1) and the safety and treatment efficacy of K9 in patients with active Thyroid Eye Disease (Cohort 2). Participants will receive study medication one time or for up to 4 weeks. Participants will have blood drawn and/or complete eye exams and questionnaires.

The planned duration of this study is 6 weeks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 8
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Cohort 1

• Subject is willing and able to receive treatment and complete corresponding assessments as required by the protocol

Cohort 2

• Diagnosed with Thyroid Eye Disease (TED).

• Symptomatic TED diagnosed no more than 9 months earlier.

• Clinical Activity Score = 3 (on 7 point scale) for the worse eye.

• Subject is willing and able to receive treatment and complete corresponding assessments as required by the protocol.

Exclusion Criteria:

Cohort 1

• Body weight less than 55 kg.

• History of any clinically significant medical disorders the principal investigator considers exclusionary, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.

• Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception.

• History or current evidence of hypersensitivity to any components of the study medication, as assessed by the investigator.

• Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary

Cohort 2

• Body weight less than 55 kg.

• Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception.

• History or current evidence of hypersensitivity to any components of the study medication, as assessed by the investigator.

• Participation in any investigational drug or ocular device study within 30 days prior to the Day 1 Study Visit.

• History or current evidence of a medical condition that may, in the opinion of the investigator, preclude the safe administration of study medication or affect the results of the study.

• Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.

• History of use of teprotumumab (Tepezza), radiotherapy, or orbital surgery.

• History (last 6 weeks) of use of systemic (oral, intravenous, or intramuscular) corticosteroids or immunosuppressants (e.g. mycophenolate), intravenous immunoglobulin, or plasmapheresis.

• Clinical activity score < 3

• Uncontrolled diabetes or hypertension

• History of mental / psychiatric disorder

• Hepatic dysfunction (Albumin (Alb), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphates levels must be within normal range for eligibility)

• Renal impairment (Urea, Creatinine, and Glomerular Filtration Rate levels must be within normal range)

• Any baseline condition that the principal investigator considers exclusionary.

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• Kamuvudine-9
96 mg tablets taken twice a day for 4 weeks
• Kamuvudine-9
96 mg tablets taken once

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Peter Timoney	Inflammasome Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Frequency of participants experiencing ocular or systemic adverse events.	6 weeks
Primary	plasma concentrations of K9	plasma concentrations measured after a single oral dose in healthy adults. For each of these time points 5 ml of blood will be drawn.	Pharmacokinetic samples collected pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after dosing
Secondary	Change in Standardized Patient Evaluation of Eye Dryness (SPEED) symptoms	The SPEED Questionnaire will be used to track progression of dry eye symptoms. The SPEED questionnaire has eight questions. The frequency and severity of symptoms are rated on a numeric scale. Scores range from 0 to 28 with higher scores equating to more symptoms.	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in Diplopia	Diplopia is assessed by the Bahn-Gorman Scale. The Bahn-Gorman scale is a subjective grading scheme that uses a scale of 0-3 to assess the severity of diplopia. A higher score equates to more severe diplopia.	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in Study Visit in Clinical Activity Score (CAS),	Clinical Activity Score (7 point scale) with higher score equating to more symptoms	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in proptosis	Hertel exophthalmometry will be used to measure the globe position of the eye by calculating the distance from the lateral orbital rim to the surface of the cornea in millimeters (mm)	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in Graves' ophthalmopathy-specific quality-of-life scale (GO-QOL)	The GO-QOL is a self-administered health-related QOL questionnaire specifically designed and validated in patients with TED. It includes 2 subscale GO-QOL scores: (1) visual functioning and (2) appearance-related, with the 2 weighted equally to create an overall score. Both the subscales and overall score are transformed to a scale of 0 to 100, 0 indicating worst health and 100 indicating best health.	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in upper eyelid retraction	upper eyelid retraction will be determined by measuring the margin reflex distance (MRD1) in millimeters. The MRD1 is the measurement in millimetres from the light reflex on the patient's cornea to the level of the centre of the upper eyelid margin, with the patient gazing in the primary position.	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in lower eyelid retraction	Lower eyelid retraction is measured by the distance from the inferior limbus to the lower eyelid, or by the margin reflex distance 2 (MRD2). The distance between the corneal light reflex to the central portion of the lower eyelid is measured in millimeters	Baseline (Day 1) and weeks 1, 4, and 6
Secondary	Change in inflammasome output cytokines	measured by ELISA	Baseline (Day 1) and weeks 1, 4, and 6