A Safety, Tolerability, PK, and PD Study of Once Weekly ISIS-FGFR4RX SC in Obese Patients

Study Overview
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Brief Summary
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The purpose of this study is to to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ISIS-FGFR4RX.

Official Title
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A Double Blind, Randomized, Placebo-controlled, Single Center, Phase 2a Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 463588 (ISIS-FGFR4RX, an Antisense Inhibitor of Fibroblast Growth Factor Receptor 4) Administered Subcutaneously Once Weekly for 13 Weeks in Obese Patients

Conditions
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Obesity

Intervention / Treatment
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* Drug: ISIS-FGFR4RX
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements Male or female patients between the age of 18-65 years, inclusive Females: Must be post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved) Males: Surgically sterile, abstinent or if engaged in sexual relations with women of childbearing potential, patient is utilizing an acceptable contraceptive method during and for 5 months after the last dose of ISIS 463588 or placebo (Study Drug) Body Mass Index (BMI) between 30.0 and 40.0 kg/m2, inclusive Patients who are willing to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures Agree to abstain from alcoholic beverages for at least 48 hours prior to clinic visits Agree to maintain current diet and exercise regimen from Screening until End-of-Study Exclusion Criteria: Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening) or physical examination Positive test for HIV, hepatitis B or C at Screening Hypothyroidism or Hyperthyroidism Weight change > 5% in the 3 months prior to Screening

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ISIS-FGFR4RX<br>ISIS-FGFR4RX administered subcutaneously | Drug: ISIS-FGFR4RX<br>* ISIS-FGFR4RX administered subcutaneously<br>* Other names: ISIS 463588;|
| Placebo Comparator: Placebo<br>Placebo administered subcutaneously | Drug: Placebo<br>* Placebo administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy Expenditure using both room calorimetry and hood (metabolic cart) calorimetry | As measured by: Resting Metabolic rate (kcal/min) Resting metabolic rate adjusted for changes in body composition (kcal/min) Resting fat oxidation (grams/24 hr) | From baseline to the average of weeks 14 and 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability will be assessed by determining the incidence, and severity of adverse effects and changes in laboratory evaluations within each treatment group. | Safety results in patients dosed with ISIS 463588 will be compared with those from patients dosed with placebo | 33 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Energy Expenditure