Clinical trial NCT03466203: Safety Study of LLF580 in Obese Volunteers
Official title: A 12 Week Phase Ib Randomized Investigator and Subject Blinded Placebo Controlled Repeat-dose Study of LLF580
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Keywords: obesity
hypertriglyceridemia
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-03-15
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability following repeated dosing of LLF580
timeFrame: 12 weeks
Secondary outcomes:
measure: LDL-C, HDL-C
timeFrame: 12 weeks
measure: serum CTX-1, P1NP, and osteocalcin
timeFrame: 12 weeks
measure: Body weight
timeFrame: 12 weeks
measure: BMI
timeFrame: 12 weeks
measure: serum BSAP
timeFrame: 12 weeks
measure: urine NTX-1
timeFrame: 12 weeks
measure: Total cholesterol
timeFrame: 12 weeks
measure: Triglycerides (fasting)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Overland Park
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Lincoln
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: High Point
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
Study officials:
References:
citation: Rader DJ, Maratos-Flier E, Nguyen A, Hom D, Ferriere M, Li Y, Kompa J, Martic M, Hinder M, Basson CT, Yowe D, Diener J, Goldfine AB; CLLF580X2102 Study Team. LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia. J Clin Endocrinol Metab. 2022 Jan 1;107(1):e57-e70. doi: 10.1210/clinem/dgab624.