Study to Evaluate HT-6184 in Healthy Subjects

NCT05447546 | Completed Phase 1 FDA Drug

• 1 other identifier: HT-6184-NHV-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to evaluate the safety and tolerability of HT-6184 when administered as single oral doses at escalating dose levels in healthy volunteer subjects. The secondary objectives of this study are to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of HT-6184. Results of the PD analyses will be used to determine the minimal biologically effective dose (MBED): the lowest dose that achieves \>70% target inhibition compared to unstimulated vehicle controls over 24 hours in 4 of 6 treated volunteers.

Conditions

Normal Healthy Subjects

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events administered as single oral doses at escalating dose levels in healthy volunteer subjects.

  Safety and tolerability of HT-6184 as measured by subject incidence of treatment-related adverse events.

  up to 6 weeks

• Incidence of abnormal laboratory test results

  Safety and tolerability of HT-6184 as measured by subject incidence of treatment-related abnormal lab values.

  up to 6 weeks

• Incidence of treatment-emergent clinically abnormal electrocardiogram (ECG)

  Safety and tolerability of HT-6184 as measured by subject incidence of treatment-related abnormal ECG.

  up to 6 weeks

• Incidence of treatment-emergent clinically abnormal physical exam

  Safety and tolerability of HT-6184 as measured by subject incidence of treatment-related abnormal physical exam.

  up to 6 weeks

Secondary Outcomes (9)

• Plasma maximum measured drug concentration (Cmax)

  up to 6 weeks

• Time of maximum concentration (Tmax)

  up to 6 weeks

• Area under the plasma concentration-time curve (AUC0-24)

  up to 6 weeks

• Area under the plasma concentration-time curve (AUC0-last)

  up to 6 weeks

• Area under the plasma concentration-time curve (AUC0-inf)

  up to 6 weeks

Study Arms (16)

1 mg HT-6184 QD

ACTIVE COMPARATOR

Cohort 1 - 6 subjects x 1 mg HT-6184 QD on Day 1

Drug: HT-6184

1 mg Placebo QD

PLACEBO COMPARATOR

Cohort 1 - 2 subjects x placebo, QD on Day 1

Drug: HT-6184 Placebo

2 mg HT-6184 QD

ACTIVE COMPARATOR

Cohort 2 - 6 subjects x 2 mg HT-6184 QD on Day 1

Drug: HT-6184

2 mg Placebo QD

PLACEBO COMPARATOR

Cohort 2 - 2 subjects x placebo, QD on Day 1

Drug: HT-6184 Placebo

3 mg HT-6184 QD

ACTIVE COMPARATOR

Cohort 3 - 6 subjects x 3 mg HT-6184 QD on Day 1

Drug: HT-6184

3 mg Placebo QD

PLACEBO COMPARATOR

Cohort 3 - 2 subjects x placebo, QD on Day 1

Drug: HT-6184 Placebo

4 mg HT-6184 QD

ACTIVE COMPARATOR

Cohort 4 - 6 subjects x 4 mg HT-6184 QD on Day 1

Drug: HT-6184

4 mg Placebo QD

PLACEBO COMPARATOR

Cohort 4 - 2 subjects x placebo, QD on Day 1

Drug: HT-6184 Placebo

1 mg HT-6184 QD x 2 weeks

ACTIVE COMPARATOR

Cohort 5 - 6 subjects x 1 mg HT-6184 QD on Day 1-5, 8-12

Drug: HT-6184

1 mg Placebo QD x 2 weeks

PLACEBO COMPARATOR

Cohort 5 - 2 subjects x 1 mg placebo, QD on Day 1-5, 8-12

Drug: HT-6184 Placebo

2 mg HT-6184 QD x 2 weeks

ACTIVE COMPARATOR

Cohort 6 - 6 subjects x 2 mg HT-6184 QD on Day 1-5, 8-12

Drug: HT-6184

2 mg Placebo QD x 2 weeks

PLACEBO COMPARATOR

Cohort 6 - 2 subjects x 2 mg placebo, QD on Day 1-5, 8-12

Drug: HT-6184 Placebo

3 mg HT-6184 QD x 2 weeks

ACTIVE COMPARATOR

Cohort 7 - 6 subjects x 3 mg HT-6184 QD on Day 1-5, 8-12

Drug: HT-6184

3 mg Placebo QD x 2 weeks

PLACEBO COMPARATOR

Cohort 7 - 2 subjects x 3 mg placebo, QD on Day 1-5, 8-12

Drug: HT-6184 Placebo

4 mg HT-6184 QD x 2 weeks

ACTIVE COMPARATOR

Cohort 8 - 6 subjects x 4 mg HT-6184 QD on Day 1-5, 8-12

Drug: HT-6184

4 mg Placebo QD x 2 weeks

PLACEBO COMPARATOR

Cohort 8 - 2 subjects x 4 mg placebo, QD on Day 1-5, 8-12

Drug: HT-6184 Placebo

Interventions

HT-6184 DRUG

Oral capsule

1 mg HT-6184 QD; 1 mg HT-6184 QD x 2 weeks; 2 mg HT-6184 QD; 2 mg HT-6184 QD x 2 weeks; 3 mg HT-6184 QD; 3 mg HT-6184 QD x 2 weeks; 4 mg HT-6184 QD; 4 mg HT-6184 QD x 2 weeks

HT-6184 Placebo DRUG

Oral capsule

1 mg Placebo QD; 1 mg Placebo QD x 2 weeks; 2 mg Placebo QD; 2 mg Placebo QD x 2 weeks; 3 mg Placebo QD; 3 mg Placebo QD x 2 weeks; 4 mg Placebo QD; 4 mg Placebo QD x 2 weeks

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female, between 18 and 65 years of age (inclusive) at Screening;
• Has a body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive) at Screening
• Is in good general health, as determined by the Investigator, without clinically significant medical history;
• Normal physical examination, 12-lead electrocardiogram (ECG), and vital signs, as determined by the Investigator;
• Clinical laboratory values within the normal limits as defined by the clinical laboratory reference range;
• Female partners of male participants of childbearing potential, and female participants of childbearing potential must agree to use a highly effective method of contraception prior to study entry, for the duration of study participation, and a minimum of 30 days after the last dose. Highly effective forms of contraception include the following:
• Established use (i.e., at least 30 days prior to enrollment) of combined (estrogen and progestogen containing) oral, intravaginal or transdermal hormonal contraception associated with inhibition of ovulation,
• Established use (i.e., at least 30 days prior to enrollment) progestogen-only oral, injectable or implantable hormonal contraception associated with inhibition of ovulation,
• Established use (i.e., at least 30 days prior to enrollment) of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS),
• bilateral tubal occlusion,
• vasectomized partner, provided that partner is the sole sexual partner of the female trial participant and that the vasectomized partner has received medical assessment of the surgical success,
• sexual abstinence, defined as refraining from heterosexual intercourse during the study, when this is in line with the preferred and usual lifestyle of the subject.
• In the case of a female of childbearing potential, has a negative serum pregnancy test (SPT) at Screening and Day -2 and is willing to submit to a SPT at the end of study (EOS);
• Negative urine test for drugs of abuse and breath test for alcohol use at Screening and check-in (Day -2). The tests may be repeated once if necessary and deemed appropriate by the Investigator;
• Agree to refrain from tobacco or nicotine containing products within 48 hours prior to Day 1 and during the periods when PK blood samples are collected;

You may not qualify if:

• A female who is pregnant, plans to become pregnant during the study, or is breastfeeding a child;
• Any clinically significant central nervous system, cardiac, pulmonary, renal, gastrointestinal (GI), endocrinological, respiratory, or metabolic conditions (or history), or other pathological or physiological conditions, that might interfere with the study results in the investigator's opinion;
• Any condition which, in the investigator's opinion, puts the participant at significant risk, could confound the study results, or may interfere significantly with the subject's participation in the study;
• Immunization within 10 days of Day 1;
• Anticipated need for surgery or hospitalization during the study;
• Consumed alcohol within 48 hours prior to Day 1 or refuses to abstain from alcohol throughout the duration of the study;
• History of heavy smoking (i.e., more than 10 cigarettes a day or the tobacco/nicotine equivalent) within 3 months of screening or refuses to abstain from tobacco or nicotine-containing products throughout the duration of the study;
• Donation or loss of blood (excluding volume drawn at screening) of ≥ 450 mL within 3 months of Day 1;
• Active or lifetime infection (e.g., negative test for human immunodeficiency virus (HIV) and hepatitis, and no history of tuberculosis and syphilis) or a history of severe infection during the 30 days prior to screening;
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment;
• Prior treatment with a NLRP3 inhibitor for any indication;
• Is unwilling or unable to refrain from using prescription medications for 30 days prior to Day 1 or over the counter medications, herbal preparations, and supplements for 14 days prior to Day 1 (excluding permitted forms of contraception and occasional use of acetaminophen \[up to 2 g in 24 hours\]);
• Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator;
• Is currently participating in any clinical trial;
• Has received any investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to study Day 1;

Sponsors & Collaborators

• Halia Therapeutics, Inc.: lead
• TKL Research, Inc.: collaborator

Study Sites (1)

TKL Research, Inc.

Fair Lawn, New Jersey, 07410, United States

Location

Study Officials

• Jesson Yeh, MD

  TKL Research, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SAD portion in 4 cohorts, with 8 subjects in each cohort, 4 ascending single doses, MAD portion in 4 cohorts, with 8 subjects in each cohort, 4 multiple ascending doses.

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: July 7, 2022
• Study Start: June 15, 2022
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: August 28, 2023

Record last verified: 2023-08

Locations

US (1)