An Efficacy, Safety and Pharmacokinetics Study of Beloranib (ZGN-440 for Injectable Suspension) in Obese Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate weight reduction, safety and pharmacokinetics for certain doses of beloranib (ZGN-440 for injectable suspension) administered as twice-weekly subcutaneous injections for 12 weeks.

Detailed Description
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This protocol is designed to test the safety and efficacy of a drug called beloranib (ZGN-440 for injectable suspension). It is to be tested for its ability to reduce weight in obese subjects. The study will provide information on how much ZGN-440 gets into the blood, how long it stays in the body, and how it affects other biological markers.

Official Title
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Randomized, Double-Blind, Placebo Controlled, Dose Ranging Phase 2 Trial of Beloranib (ZGN-440 for Injectable Suspension), A Novel Methionine Aminopeptidase 2 Inhibitor, in Obese Subjects to Evaluate Weight Reduction, Safety, and Pharmacokinetics Over 12 Weeks

Conditions
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Obesity

Intervention / Treatment
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* Drug: Beloranib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese volunteers weighing ≥ 50 kg BMI ≥ 30 and ≤ 50 kg/m2 Stable body weight during the past 2 months Type 2 diabetes mellitus is allowed Exclusion Criteria: Use of weight loss agents in the past month Current, clinically significant eating disorder Type 1 diabetes mellitus

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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Accepts Healthy Volunteers

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>ZGN-440 sterile diluent | Drug: Placebo<br>* Subjects will receive placebo twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses.<br>* Other names: ZGN-440 sterile diluent;|
| Experimental: 0.3 mg Beloranib<br>0.3 mg ZGN-440 for injectable suspension | Drug: Beloranib<br>* Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.<br>* Other names: ZGN-433;|
| Experimental: 0.6 mg Beloranib<br>0.6 mg ZGN-440 for injectable suspension | Drug: Beloranib<br>* Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.<br>* Other names: ZGN-433;|
| Experimental: 1.2 mg Beloranib<br>1.2 mg ZGN-440 for injectable suspension | Drug: Beloranib<br>* Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.<br>* Other names: ZGN-433;|
| Experimental: 2.4 mg Beloranib<br>2.4 mg ZGN-440 for injectable suspension | Drug: Beloranib<br>* Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.<br>* Other names: ZGN-433;|
| Experimental: 3.2 mg Beloranib<br>3.2 mg ZGN-440 for injectable suspension | Drug: Beloranib<br>* Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.<br>* Other names: ZGN-433;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of beloranib (ZGN-440 for injectable suspension) administered subcutaneously for 12 weeks | Safety and tolerability of beloranib will be assessed by comparing frequency and severity of adverse events as well as changes in physical examinations, ECGs, vital signs and laboratory evaluations. Other safety oriented questionnaires and parameters (e.g. sleep quality, hemodynamic parameters) will be measured and evaluated. | Up to 26 weeks | 
| Weight loss and responses in metabolic biomarkers over a dose range of ZGN-440 | Change from baseline in body weight and body composition (bioimpedance assessments), and scores of hunger/appetite over the dosing period will be evaluated to document beloranib's effect on obesity. Biomarkers of lipid metabolism will be measured to assess possible mechanisms of loss of body fat, as well as endocrinologic or anti-inflammatory markers. | Up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics over a dose range of beloranib | The plasma PK of beloranib and selected metabolites may be assessed following dose administration to compare systemic exposure and PK parameters over the range of doses. PK parameters include Cmax, Tmax, AUC24hour, AUC∞, volume of distribution, total clearance, terminal elimination constant, and half-life. Mean residence time may also be reported. | Up to 12 weeks | 
| Compare the plasma pharmacokinetic profile of beloranib administered subcutaneously with the profiles obtained previously using an alternative formulation administered subcutaneously and with ZGN-433 (beloranib hemioxalate) administered intravenously |  | Up to 12 weeks | 
| Apparent bioavailability over a dose range of beloranib | Bioavailability will be estimated from the SC PK parameters compared to the profile from comparable doses in earlier IV administration studies. | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obese, Obesity, Overweight, Weight loss, Weight reduction, Beloranib