Clinical trial NCT03604419: Dose-finding of PB-119 Administered Subcutaneously Once Weekly Versus Placebo in Subjects With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus (T2DM)
Lead sponsor: PegBio Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Covance
First posted: 2018-07-27
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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);

Primary outcomes:
measure: The change from baseline value of HbA1c will be compared between treatments
timeFrame: From Baseline to end of treatment (up to Week 12)
Secondary outcomes:
measure: The change from baseline value of Fasting Plasma Glucose at Weeks 2, 4, 8, and 12
timeFrame: From Baseline to end of treatment (up to Week 12)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
Study officials:
References:
citation: 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.