A Ph2 Study to Evaluate the Safety, Efficacy and Tolerability of HT-6184 and Semaglutide in Obese Participants With T2DM

NCT07172867 | Withdrawn Phase 2 DMC

• 1 other identifier: HT-6184-IIO-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ofirnoflast in combination with semaglutide in comparison to semaglutide alone in obese participants with T2DM.

Conditions

Diabetes Mellitus, Type 2; Obesity

Outcome Measures

Primary Outcomes (2)

• Assess glycemic control using HbA1c (%)

  Evaluate glycemic control using HbA1c (%) from baseline to week 12 in participants treated with ofirnoflast or placebo in combination with semaglutide. This outcome will assess if the participant was able to reduce HbA1c by at least 1.5%.

  From first dose through End of Study (up to 12 weeks per participant)

• Assess weight loss using body weight measurements

  Evaluate weight loss using body weight measurements from baseline to week 12 in participants treated with ofirnoflast or placebo in combination with semaglutide. This outcome will assess if the participant was able to reduce body weight by at least 5%.

  From first dose through End of Study (up to 12 weeks per participant)

Secondary Outcomes (6)

• Assess the change in HbA1c (% point)

  From first dose through End of Study (up to 12 weeks per participant)

• Assess the change in body composition utilizing DEXA body scan

  From first dose through End of Study (up to 12 weeks per participant)

• Assess the PK profile; AUC 0-inf, AUC 0-last, AUC tau, Cmax, tmax, t1/2, and Cl/F

  From first dose through End of Study (up to 12 weeks per participant)

• Assess number of participants who experience Serious Adverse Events (SAEs)

  From first dose through End of Study (up to 12 weeks per participant)

• Assess number of participants who experience treatment emergent adverse events (TEAEs)

  From first dose through End of Study (up to 12 weeks per participant)

Study Arms (2)

HT-6184 2mg Treatment

EXPERIMENTAL

Ofirnoflast (2 mg): dosed once a day, orally (PO QD) + semaglutide (1 mg): dosed weekly (q1wk), via subcutaneous (SC) injection for 12 weeks.

Drug: HT-6184; Drug: Semaglutide 1 mg

HT-6184 2mg Matching Placebo

PLACEBO COMPARATOR

Placebo: dosed once a day, orally (PO QD) + semaglutide (1 mg): dosed weekly (q1wk), via SC injection for 12 weeks.

Drug: HT-6184 Matching Placebo; Drug: Semaglutide 1 mg

Interventions

HT-6184 DRUG

2mg QD

HT-6184 2mg Treatment

HT-6184 Matching Placebo DRUG

2mg QD

HT-6184 2mg Matching Placebo

Semaglutide 1 mg DRUG

Semaglutide 1 mg, every week

HT-6184 2mg Matching Placebo; HT-6184 2mg Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• BMI between 27 kg/m2 and 40 kg/m2.
• Stable body weight (± 5 kg) within 90 days of screening, and body weight \<150 kg.
• HbA1c is 7.5-10.5% at screening.
• Established diagnosis of T2DM.
• Receiving a stable 1mg SC q1wk dose of semaglutide (Ozempic®) for ≥ 90 days prior to signing informed consent.
• Females must meet one of the following:
• Postmenopausal (\>45 years of age with amenorrhea for at least 12 months, without using exogenous hormonal contraception and with FSH ≥ 40 IU/L).
• Surgically sterile (hysterectomy, bilateral salpingectomy; oophorectomy) for at least 6 months.
• Using a double contraception including a barrier method (condom, diaphragm, or occlusive cap) and a highly effective method of birth control, which includes the following:
• i. Established use (i.e. at least 90 days prior to signing of ICF) of combined (estrogen and progestogen) oral, intravaginal, or transdermal hormonal contraceptive associated with inhibition of ovulation ii. Established use (i.e. at least 90 days prior to signing of ICF) of progestogen-only oral, injectable, or implantable hormonal contraceptive associated with inhibition of ovulation iii. Established use (i.e. at least 90 days prior to signing of ICF) of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) iv. Bilateral tubal occlusion completed at least 90 days prior to signing of ICF d. Vasectomized partner with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate. Participant must provide documentation before the first dose of ofirnoflast (study day 1).
• e. Sexual abstinence, when this is in line with the preferred and usual lifestyle of the participant
• Male participants who are sexually active with a woman of childbearing potential must agree to use a double contraception including a barrier method (male condom) and a highly effective method of contraception (highly effective methods of contraception are listed above) during the study and for 30 days after the last dose of ofirnoflast/ placebo.
• In the case of WOCBP, participants must have a negative serum pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) at screening and negative urine pregnancy tests on first day of dosing and at each study visit.

You may not qualify if:

• Any prescription or over-the-counter medications intended for weight loss within 6 months of screening, excluding semaglutide.
• History of, or known hypersensitivity to, monoclonal antibody drugs or a contraindication to semaglutide (e.g. Ozempic® or Wegovy®)
• Use of other investigational drugs at the time of screening or within 30 days or 5 half-lives prior to signing of the ICF, whichever is longer, or longer if required by local regulations
• Previous or current diagnosis of Type 1 diabetes mellitus (T1DM) or current gestational diabetes.
• Diagnosis of T2DM requiring current use of insulin, repaglinide, saxagliptin, and sulfonylureas.
• History of diabetic ketoacidosis (within 90 days of screening), or proliferative or severe retinopathy (i.e., retinopathy requiring acute treatment).
• Previous bariatric surgery, liposuction, or planned weight loss surgery.
• Current or past diagnosis of pancreatitis
• Current or past diagnosis of severe gastroparesis
• Personal or within first-degree relative family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
• Calcitonin ≥20 ng/L measured by central laboratory at screening (individuals with elevated calcitonin at initial screening may be re-screened)
• Laboratory abnormalities at screening
• Current or history of clinically significant (per Investigator's judgment) liver or biliary disease or significantly abnormal LFT at screening (see above)
• Current acute or chronic self-reported HCV and/or HBV infection
• Current or history of clinically significant renal disease (per Investigator's judgment) or eGFR\<60mL/min/1.73m2

Sponsors & Collaborators

• Halia Therapeutics, Inc.: lead

Study Sites (1)

Cleveland Clinic Abu Dhabi

Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 15, 2025
• Study Start: January 6, 2026
• Primary Completion: January 23, 2026
• Study Completion: January 23, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)