Clinical trial NCT03656744: A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)
Official title: A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fatty Liver, Nonalcoholic
NAFLD
Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Digestive System Diseases
Type 2 Diabetes Mellitus (T2DM)
Lead sponsor: HighTide Biopharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2018-09-04
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.

Detailed description: This 18-week randomized, double-blind, parallel-group, proof of concept (POC), dose-ranging study compared multiple doses of HTD1801 to placebo in a 1:1:1 ratio. Since accumulation of hepatic fat is considered the "first hit" in the pathogenesis of NASH (Adams and Angulo 2006), change in liver fat content (LFC) by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF) is an appropriate primary endpoint and is consistent with that used in other recent Phase 2 POC studies in NASH (Harrison et al., 2018, Madrigal Pharmaceuticals 2018).

The Harrison et al., 2018, Madrigal Pharmaceuticals 2018 study showed clinically meaningful absolute and relative reductions in LFC assessed by MRI-PDFF over 12-week treatment periods thus, it was considered that an 18 week HTD1801 treatment period would therefore be adequate to assess the study's primary endpoint and to maximize collection of exposure and safety related data.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of NASH as assessed by MRI
* Clinically documented diagnosis of T2DM
* Body mass index (BMI) \>25 kg/m2

Exclusion Criteria:

* Liver disease unrelated to NASH
* Poorly controlled T2DM or Type 1 Diabetes Mellitus
* History of alcohol or substance abuse or dependence
* Inability to undergo MRI for any reason
* History of significant cardiovascular disease

Primary outcomes:
measure: Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
timeFrame: Baseline through study Week 18
Secondary outcomes:
measure: Change in Fasting Glucose
timeFrame: Baseline through study Week 18
measure: Changes in Hemoglobin A1c
timeFrame: Baseline through study week 18
measure: Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF
timeFrame: Baseline through study week 18
measure: Relative Change in LFC as Measured by MRI-PDFF
timeFrame: Baseline through study week 18
measure: Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF
timeFrame: Baseline through study Week 18
measure: Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF
timeFrame: Baseline through study Week 18
measure: Change in HOMA-IR
timeFrame: Baseline through study week 18
measure: Change in LDL-c
timeFrame: Baseline visit through study week 18
measure: Change in Serum Triglycerides
timeFrame: Baseline through study week 18
measure: Change in HDL-c
timeFrame: Baseline through study week 18
measure: Change in AST
timeFrame: Baseline through study week 18
measure: Change in ALT
timeFrame: Baseline through study week 18
measure: Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18
timeFrame: Baseline through study week 18
measure: Change in Pro-Peptide of Type III Collagen (Pro-C3)
timeFrame: Baseline through study week 18
measure: Change in ELF Score
timeFrame: Baseline through study week 18
measure: Change in TIMP-1
timeFrame: Baseline through study week 18
measure: Change in PIIINP
timeFrame: Baseline through study week 18
measure: Change in HA
timeFrame: Baseline through study week 18
measure: Change in Total Bile Acids
timeFrame: Baseline through study week 18
measure: Change in FGF19
timeFrame: Baseline through study week 18
measure: Number of Participants Reporting an Adverse Events From Baseline Through Week 18
timeFrame: Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks in total for a completed subject.
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Institute for Liver Health
state: Arizona
city: Tucson
country: United States
facility: Institute for Liver Health
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research
state: Arizona
city: Panorama City
country: United States
facility: National Research Institute
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Fayetteville
country: United States
facility: Cumberland Research Associates
state: North Carolina
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Hermitage
country: United States
facility: Digestive Health Research
state: Tennessee
city: Austin
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Edinburg
country: United States
facility: Doctors Hospital at Renaissance
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: HighTide Therapeutics USA, LLC
name: Adrian Di Bisceglie, MD,FACP,FAASLD
role: STUDY_DIRECTOR
References:
citation: Harrison SA, Gunn N, Neff GW, Kohli A, Liu L, Flyer A, Goldkind L, Di Bisceglie AM. A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun. 2021 Sep 17;12(1):5503. doi: 10.1038/s41467-021-25701-5.