Dose-finding of PB-119 Administered Subcutaneously Once Weekly Versus Placebo in Subjects With Type 2 Diabetes

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of Twelve Once-weekly Subcutaneous Doses of PB-119 to Patients With Type 2 Diabetes Mellitus (T2DM) Not Well-controlled by Metformin Monotherapy

A phase 2, multicenter study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin mono therapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: PB-119 150 μg+ Glucophage®; Drug: PB-119 200 μg+ Glucophage®; Drug: PB-119 placebo + Glucophage®; Drug: PB-119 100 μg+ Glucophage®

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort, multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of PB-119 to patients with T2DM not well-controlled by metformin monotherapy. Patients will be assessed for eligibility over a 2 week screening period prior to a 4-week run-in period and a 12-week double-blind treatment period.A phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin monotherapy The eligible patients will be randomized to 1 of 3 dose cohorts (A, B, or C). Each patient will subsequently be randomized within the designated cohort to 1) active drug or placebo at a 3:1 active drug:placebo ratio and 2) exclusion from or inclusion in the pharmacokinetic (PK) blood sample collection subgroup at a 3:1 excluded:included ratio

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients in whom T2DM has been diagnosed according to 2018 American Diabetes Association T2DM diagnostic criteria, have made lifestyle modifications (ie, diet and exercise) for at least 3 months prior to Screening, and have been taking metformin for at least 3 months before Screening with a stable dosage for at least 8 weeks (stable dosage is defined as metformin dosage ≥1500 mg/day or maximum tolerated dose).
2. Males and/or females between the ages of ≥18 and ≤70 years at Screening
3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1, Visit 3.1;
4. FPG ≥126 and ≤240 mg/dL (≥7.0 and ≤13.3 mmol/L) at Screening and at Week -1, Visit 3.1;
5. Body mass index (BMI) ≥18.5 and ≤40.0 kg/m2 at Screening, with inclusion of patients with BMIs at the lower end of the range enrolled into the study to enable comparisons across BMI range;

Exclusion Criteria:

1. Medical history or current diagnosis of:

   1. Type 1 diabetes mellitus, diabetes caused by pancreas injury or by other diseases (like acromegaly or Cushing syndrome);
   2. Diabetes acute complication, like ketoacidosis or hyperosmolar coma;
   3. Diagnosed proliferative retinopathy;
   4. 3 instances of severe hypoglycemia (events during which the patient required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions; episodes may be associated with sufficient neuroglycopenia to have induced seizure or coma) in the 6 months prior to Screening;
   5. Significant vascular disease;
2. Current/ongoing diagnosis of any type of malignant tumor or evidence of recurrence in the 6 months prior to Screening (patients who have been stable for ≥6 months or those who have had basal or squamous cell skin cancers removed and have no evidence of recurrence will not be excluded). Patients with a medical history of any other type of cancer in the last 5 years prior to Screening will be excluded;
3. Severe cardiovascular diseases occurring within 6 months prior to Screening (eg, congestive heart disease, myocardial infarction, acute coronary syndrome, apoplexy, transient ischemic attack);

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PB-119 100 μg; PB-119 100 μg subcutaneous (SC) once weekly (QW) + Metformin oral (p.o.) Glucophage® (stable dosage)	Drug: PB-119 150 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 200 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 placebo + Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo
Experimental: PB-119 150 μg; PB-119 150 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)	Drug: PB-119 200 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 placebo + Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 100 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo
Experimental: PB-119 200 μg; PB-119 200 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)	Drug: PB-119 150 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 placebo + Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 100 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo
Placebo Comparator: PB-119 Placebo; PB-119 Placebo SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)	Drug: PB-119 150 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 200 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo; Drug: PB-119 100 μg+ Glucophage®; Each patient will subsequently be randomized within the designated cohort to active drug or placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change from baseline value of HbA1c will be compared between treatments	From Baseline to end of treatment (up to Week 12)

Secondary Outcome Measures

Outcome Measure	Time Frame
The change from baseline value of Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	From Baseline to end of treatment (up to Week 12)

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Collaborators: Covance

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2018
• Primary Completion (Actual): July 23, 2019
• Study Completion (Actual): July 23, 2019

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: PB119202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No