Study to Assess the Safety, Tolerability, Pharmacokinetic of Thrv-1268

NCT ID: NCT06507839

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-15
• Study Completion Date: 2024-11-01

Brief Summary

This is a single-center, randomized, double-blind, placebo-controlled study to be conducted in 2 parts: single ascending dose (SAD) incorporating a food effect arm and multiple ascending dose (MAD). Potential participants for each part will undergo screening procedures within 28 days of enrollment.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Single Ascending Dose (SAD) THRV-1268

5 dosing cohorts will receive a single oral dose of THRV-1268. The highest dose of THRV-1268 to be administered is 500 mg.

Group Type: EXPERIMENTAL

THRV-1268

Intervention Type: DRUG

THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Food Effect THRV-1268

food effect will be integrated into one of the SAD cohorts as a single dose, two-period with at least a 7-day washout, crossover cohort.

Group Type: EXPERIMENTAL

THRV-1268

Intervention Type: DRUG

THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Multiple Ascending Dose (MAD) THRV-1268

3 dosing cohorts will receive THRV-1268 in the morning on Day 1 to Day 7.

Group Type: EXPERIMENTAL

THRV-1268

Intervention Type: DRUG

THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Single Ascending Dose (SAD) Placebo

5 dosing cohorts will receive a single oral dose of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo

Food Effect Placebo

Food effect will be integrated into one of the SAD cohorts as a single dose, two-period with at least a 7-day washout, crossover cohort.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo

Multiple Ascending Dose (MAD) Placebo

3 dosing cohorts will receive placebo in the morning from Day 1 to Day 7.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo

Interventions

THRV-1268

THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Intervention Type: DRUG

Placebo

Matching placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1.Provision of signed and dated Informed Consent Form (ICF). 2.Stated willingness to comply with all study procedures and availability for the duration of the study.

3.Healthy adult male or female subjects. 4.If female, meets one of the following criteria:

• Women of childbearing potential who agrees to use any of the acceptable contraceptive methods:

1. Abstinence from heterosexual intercourse from Screening through at least 30 days from last study dose.

2. One of the following highly-effective contraception methods:

1. systemic contraceptives (combined birth control pills, injectable/implant/ insertable hormonal birth control products, or transdermal patch) used from at least 28 days prior to Screening through to at least 30 days from last study dose

2. intrauterine device (with or without hormones) used from at least 28 days prior to Screening through to at least 30 days from last study dose

3. male partner vasectomized at least 6 months prior to Screening visit

3. One of the following double-barrier contraception methods used from Screening through at least 30 days from last study dose

1. Male condom used simultaneously with diaphragm plus spermicide

2. Male condom used simultaneously with cervical cap plus spermicide Or

Or

• Surgically sterile, defined as those who have had hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, or bilateral tubal ligation.

5.Men who are biologically capable of fathering children must agree and commit to use an adequate form of contraception (see female criteria 3) for the duration of the treatment period and for no less than 90 days after the last study dose. A male subject is considered capable of fathering children even if his sexual partner is sterile or using contraceptives.

6.Men who are biologically capable of fathering children must also agree to refrain from sperm donation for the duration of the treatment period and for at least 90 days after the last study dose.

7.Aged at least 18 years but not older than 60 years (inclusive). 8.Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively. 9.Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration).

10.Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings in the physical examination (including vital signs) and/or ECG, as determined by an Investigator.

Exclusion Criteria

1. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition, which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.

2. Clinically significant abnormal findings on the physical examination or medical history during Screening as deemed by the Investigator.

3. Female who is lactating.

4. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration.

5. Male subjects with a history of oligospermia or azoospermia or any other disorder of the reproductive system.

6. Male subjects who are undergoing treatment or evaluation for infertility.

7. The average of 3 measurements performed approximately 5 min apart: Screening or baseline (Day -1) diastolic BP <50 mmHg or >95; systolic BP <100 mmHg or >145 mmHg; or HR ≤ 50 beats per minute (bpm) using a validated digital BP device. These can be repeated in triplicate once after an additional quiet resting period.

8. Orthostatic BP performed after sitting quietly for at least 4 minutes and then standing for 2 minutes with a duplicate set performed after at least 3 minutes of sitting, with a reduction in systolic BP >20 mmHg, a reduction in diastolic BP >10 mmHg, or an increase in HR >20 bpm using a validated digital BP device.

9. Estimated creatinine clearance < 80 mL/min at Screening.

10. History of significant hypersensitivity to THRV-1268, kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.

11. Screening 12-lead ECG demonstrating at least one of the following: PR >220 ms; QRS >110 ms, or QTcF >440 ms; atrioventricular block; branch bundle block, significant ST-T wave abnormalities or flat T waves that could interfere with QT analysis. Heart rate ≤50 bpm or >100 bpm.

12. History or evidence of any of the following: myocardial infarction; cardiac valvulopathy; cardiac surgery revascularization (coronary artery bypass grafting or percutaneous, transluminal coronary angioplasty); unstable angina; cerebrovascular accident, stroke, or transient ischemic attack; pacemaker; AF, flutter, or nonsustained or sustained ventricular tachycardia; orthostatic hypotension or orthostatic dizziness or lightheadedness, pulmonary arterial hypertension; sick sinus syndrome, second- or third-degree atrioventricular block; uncontrolled hypertension; congestive heart failure; personal or family history of sudden death or long QT syndrome; unexplained syncope or syncope within the last 3 years regardless of etiology.

13. Immunization with a Coronavirus Disease (COVID-19) vaccine in the 14 days prior to the first study drug administration.

14. Scheduled immunization with a COVID-19 vaccine during the study that, in the opinion of an Investigator, could potentially interfere with subject participation, subject safety, study results, or any other reason.

15. Use of immunosuppressant in the 28 days or 5 half-lives (whichever is longer) prior to the first study drug administration.

16. Major surgery with prolonged immobilization in the 28 days prior to the first study drug administration.

17. Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).

18. Any clinically significant illness in the 28 days prior to the first study drug administration.

19. Use of any over-the-counter or nutritional supplements in the last 7 days prior to the first study drug administration and during the study, that in the opinion of an Investigator would put into question the status of the subject as healthy.

20. Use of any prescription drugs (except for hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the subject as healthy.

21. Use of St. John's wort in the 28 days prior to the first study drug administration.

22. Any history of tuberculosis.

23. Hemoglobin value below the lower limit of the reference laboratory at Screening, unless deemed non-significant by the Investigator.

24. Abnormal screening values in potassium, magnesium, alanine transaminase (ALT), aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin values, unless deemed non-significant by the Investigator.

25. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration.

26. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests.

27. Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.

28. History of prior administration of THRV-1268 or inclusion in a previous cohort for this clinical study.

29. Intake of an IP or participation in a clinical trial in the 28 days or 5 half-lives (whichever is longer) prior to the first study drug administration.

30. Unable or unwilling to adhere to the lifestyle and dietary requirements described in Section 4.4.

31. Special diet or substantial changes in eating habits in the last 1 month before Screening.

32. Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration.

33. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Thryv Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Altasciences

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

0269

Identifier Type: -

Identifier Source: org_study_id