Safety Study of LLF580 in Obese Volunteers

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the safety and tolerability of multiple doses of LLF580 administered subcutaneously over 3 months in obese subjects. In addition, the study will also determine early efficacy signals in various metabolic diseases associated with elevated triglycerides and/or obesity.

Official Title
-----------------
A 12 Week Phase Ib Randomized Investigator and Subject Blinded Placebo Controlled Repeat-dose Study of LLF580

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Biological: LLF580
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) within the range of 30 to 45 kg/m2, inclusive, with ethnic adjustment (≥27.5 kg/m2 for Asian individuals). Fasting triglyceride 150 - 500 mg/dL (1.69 - 5.65 mmol/L), inclusive, at screening. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Exclusion Criteria: History of hepatobilliary disease. Liver disease or liver injury as indicated by abnormal liver function tests. Chronic infection with Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV). Fasting triglycerides greater than or equal to 500 mg/dL [5.65 mmol/L], or concomitant use of drug treatment for hypertriglyceridemia (fibrates, omega-3 fatty acids, nicotinic acid). History of pancreatic injury or pancreatitis. History of hypersensitivity to drugs of similar biological class, FGF21 protein analogue, or Fc fusion proteins. History of bone disorders or low vitamin D level. Contraindications to MRI. Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months). Use of weight loss drugs. Enrollment in a diet, weight loss or exercise programs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LLF580<br>LLF580 every 28 days * 3 | Biological: LLF580<br>* LLF580 300mg<br>|
| Placebo Comparator: Placebo<br>Placebo to LLF580 every 28 days * 3 | Drug: Placebo<br>* Placebo to LLF580<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability following repeated dosing of LLF580 | To assess the safety and tolerability in obese subjects following repeated dosing of LLF580 by subcutaneous (SC) injection over 12 weeks. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C, HDL-C | To assess the effects of LLF580 on lipid profiles. | 12 weeks | 
| serum CTX-1, P1NP, and osteocalcin | To assess the potential effects of LLF580 on these biomarkers. | 12 weeks | 
| Body weight | To assess the effects of LLF580 on weight. | 12 weeks | 
| BMI | To assess the effects of LLF580 on BMI | 12 weeks | 
| serum BSAP | To assess the potential effects of LLF580 on these biomarkers. | 12 weeks | 
| urine NTX-1 | To assess the potential effects of LLF580 on these biomarkers. | 12 weeks | 
| Total cholesterol | To asses the effects of LLF580 on lipid profiles | 12 weeks | 
| Triglycerides (fasting) | To assess the effects of LLF580 on lipid profiles | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, hypertriglyceridemia