RecruitingPhase 1ACTRN12624001111561

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple- Ascending Dose Study to Evaluate the Safety and Tolerability of OLX75016 in Healthy Volunteers and Patients with Non-Alcoholic Fatty Liver Disease.

Sponsor

OliX AU Pty Ltd

Enrollment

40 participants

Start Date

Jul 3, 2024

Study Type

Interventional

Conditions

Cirrhosis Fibrosis

Summary

OLX75016 is being developed by OliX Pharmaceuticals as a treatment for patients with treatment of nonalcoholic steatohepatitis (NASH) and liver fibrosis. This study will evaluate the safety and tolerability of single and multiple ascending doses of OLX75016 in patients with non-alcoholicfatty liver disease (NAFLD). This study will be conducted in 2 parts : Part A (Single ascending dose) and PartB (Multiple ascending dose). Up 20 patients with NAFLD are expected to be engaged with the study for up to 87 days in Part A or up to 172 days in Part B of the study. OLX75016 and matching placebo will be administered as SC injections in the abdominal region in this study. Part A- Following confirmation of eligibility, patients with NAFLD will be randomized to receive OLX75016 or placebo prior to dose administration on Day 1. All patients with NAFLD will be confined to the clinic until the completion of all safety/tolerability and PK assessmentson Day 3. Participants will be required to return to the clinic for additional outpatient safety/tolerability assessments on Day 4, 7, 14, 28, 42, 84, 112, 140, 168, 196 and 224. Participants will be discharged from each visit following completion of all safety and PK assessments, the end of study (EoS) visit will be on Day 224. Part B - Following confirmation of eligibility, patients with NAFLD will be randomized to receive OLX75016 or placebo prior to dose administration on Day 1 and Day85. All patients with NAFLD will be confined to the clinic from day prior to dosing until the completion of all safety/tolerability and PK assessments 3 days post-dose and will be discharged following completion of all safety and PK assessments on Day 3. Patients with NAFLD will be required to attend the clinic on Days 4, 7, 14, 28 and 56 for safety and tolerability assessments. Patients with NAFLD will return to the clinic for a second confinement period from Day 84 to Day 87, with the second dose of OLX75016 or placebo administered on Day 85. NAFLD patients will be required to attend the clinic on Days 88, 91, 98, 112, 140, 169 for safety and tolerability assessments before the EoS visit on Day 253. It is hoped that the information learned from this study will help the sponsor learn more about how best to treat patients suffering from NASH and liver fibrosis in future. This research may also give rise to new or improved improvements.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Plain Language Summary

Simplified for easier understanding

Non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat builds up in the liver, and in some people it progresses to a more serious form involving inflammation and scarring (called NASH). There are limited treatment options currently available. This Phase 1 study is testing a new injectable medication called OLX75016, which is designed to target one of the biological pathways that drives fat accumulation and liver damage. Participants will receive either OLX75016 or a placebo as an injection under the skin, with either a single dose or multiple doses depending on the study phase. The main goal is to check that the medication is safe and well-tolerated, rather than to test whether it works — that comes in later trials. Participants will attend regular clinic visits over several months for safety monitoring and blood tests. You may be eligible if you are 18 to 65 years old, have a BMI between 27 and 40, and have been diagnosed with NAFLD confirmed by MRI scan. Pregnancy, certain liver or kidney conditions, blood disorders, or recent major illness may make you ineligible. This is an early-stage study to establish whether OLX75016 is safe enough to move forward with further research.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

OLX75016 is a chemically synthesized double stranded siRNA targeting expression of the Mitochondrial Amidoxime Reducing Component 1 (MARC1) enzyme for the treatment of nonalcoholic fatty liver disease(NAFLD) with liver fibrosis. OLX75016, which is administered by subcutaneous (SC) injection, OLX75016 and a matching placebo will be administered as SC injections in the abdominal region. This study will be conducted in two parts: Part A (SAD) and Part B (MAD). Each study part will enrol patients with Non-Alcoholic Fatty Liver Disease (NAFLD). - Part A (SAD) NAFLD Patients: Up to 20 patients over 3 cohorts - Part B (MAD) NAFLD Patients: Up to 12 patients over 2 dose escalation cohorts and an optional Cohort 3 - Part A Single Ascending Dose (SAD) NAFLD Patients: NAFLD patients will be enrolled and randomized to 3 cohorts with first cohort having 4 participants, second and third cohorts having 8 participants to receive single doses of OLX75016 or placebo (ratio 3:1 active: placebo). The dose levels will be 90 mg (Cohort 1), 200 mg (Cohort 2) and 45 mg (Cohort 3). At the discretion of the study Sponsor, in consultation with the Safety Review committee (SRC), additional cohorts may be added to evaluate intermediate dose levels. Patients with NAFLD will be screened between Day -28 to Day -2. Eligible participants will be admitted to the clinic on Day -1. Following confirmation of eligibility, participants will be randomized to receive OLX75016 or a placebo before dose administration on Day 1. Doses will be administered in the clinic, under the supervision of site staff . All participants will be confined to the clinic until the completion of all safety/tolerability and PK assessments on Day 3. Sentinels are not required for NAFLD patient cohorts. Participants will be required to return to the clinic for additional outpatient safety/tolerability assessments on Day 4, 7, 14, 28, 42, 84, 112, 140, 168, 196 and 224. Participants will be discharged from each visit following completion of all safety and PK assessments, the end of study (EoS) visit will be on Day 224. Compliance will be monitored by site staff witnessing of dosing and will be documented in participant study files. If participants experience any clinically significant (CS) AEs during the confinement period, they may remain in the clinical facility for further observation at the discretion of the Principal Investigator (PI). - Part B Multiple Ascending Dose (MAD) NAFLD Patients: NAFLD patients will be enrolled and randomized to 2 cohorts (Cohort 1 n=4 and Cohort 2 n=8 per cohort) and if required an optional Cohort 3 (n=8) to receive multiple doses of OLX75016 or placebo (ratio 3:1 active: placebo), with 2 dose levels planned (administered approximately 3 months apart on Day 1 and Day 85). The dose levels will be 30 mg (Cohort 1), 150 mg (Cohort 2) and dose level for Optional Cohort 3 will be based on review of safety data. At the discretion of the study Sponsor, in consultation with the SRC, additional cohort(s) may be added to evaluate (an) additional dose level(s). Dosing in MAD NAFLD Cohort 2 may commence 28 days after the first participant in MAD NAFLD Cohort 1 has completed first dose administration. Sentinel dosing will not be required in Part B (MAD), unless recommended by the SRC following review of data from Part A (SAD). Dosing in each patient cohort will commence only after SRC confirms dosing in SAD NAFLD Cohort 3. Compliance will be monitored by site staff witnessing of dosing and will be documented in participant study files. If patients with NAFLD experience any clinically significant (CS) AEs during the confinement period, they may remain in the clinical facility for further observation at the discretion of the Principal Investigator (PI).