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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Beloranib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Q-Pharm Clinics, Royal Brisbane and Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; ZGN-440 sterile diluent	Drug: Placebo; Subjects will receive placebo twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses.; Other Names: ZGN-440 sterile diluent
Experimental: 0.3 mg Beloranib; 0.3 mg ZGN-440 for injectable suspension	Drug: Beloranib; 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.; Other Names: ZGN-440 for injectable suspension; ZGN-440; ZGN-433
Experimental: 0.6 mg Beloranib; 0.6 mg ZGN-440 for injectable suspension	Drug: Beloranib; 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.; Other Names: ZGN-440 for injectable suspension; ZGN-440; ZGN-433
Experimental: 1.2 mg Beloranib; 1.2 mg ZGN-440 for injectable suspension	Drug: Beloranib; 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.; Other Names: ZGN-440 for injectable suspension; ZGN-440; ZGN-433
Experimental: 2.4 mg Beloranib; 2.4 mg ZGN-440 for injectable suspension	Drug: Beloranib; 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.; Other Names: ZGN-440 for injectable suspension; ZGN-440; ZGN-433
Experimental: 3.2 mg Beloranib; 3.2 mg ZGN-440 for injectable suspension	Drug: Beloranib; 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.; Other Names: ZGN-440 for injectable suspension; ZGN-440; ZGN-433

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zafgen, Inc.
• Investigators: Principal Investigator: J K Marjason, MD, Q-Pharm Clinics, Royal Brisbane and Women's Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 16, 2012

Study Record Updates

• Last Update Posted (Estimate): July 14, 2016
• Last Update Submitted That Met QC Criteria: July 13, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Obese; Weight loss; Weight reduction; Beloranib
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; CKD732
• Other Study ID Numbers: ZAF-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No