Dose-finding of PB-119 Administered Subcutaneously Once-weekly Versus Placebo in Drug-naïve T2DM Subjects

Phase 2

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: PB-119 75ug; Drug: PB-119 150ug; Drug: PB-119 200ug; Drug: placebo

• Registration Number: NCT03520972
• Lead Sponsor: PegBio Co., Ltd.

Brief Summary

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 in drug-naïve subjects with T2DM.

Detailed Description

Subjects will be assessed for eligibility over a 2-week screening period prior to a 2-week run-in period and a 12-week double-blind treatment period,4-week follow up period. 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 active drug or placebo at a 3:1 active drug:placebo ratio.

Study Timeline

• Study First Submitted: 2018-04-18
• Study First Submitted QC: 2018-04-27
• Study First Posted: 2018-05-11
• Study Start: 2018-06-05
• Primary Completion: 2019-07-29
• Study Completion: 2019-07-29
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-21
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 251

Inclusion Criteria

1. Males and/or females between the ages of ≥18 and ≤70 years at Screening
2. Patients in whom T2DM has been diagnosed according to 1999 WHOT2DM diagnostic criteria
3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1
4. Body mass index (BMI) ≥18.5 and ≤35.0 kg/m2 at Screening

Exclusion Criteria

1. Female who is pregnant, intends to become pregnant or breast-feeding or is of child-bearing potential and not using adequate contraception methods throughout the trial
2. Treatment with any glucose lowing agent(s) within 3 months prior to screening.An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness
3. Calcitonin ≥50 ng/L at screening
4. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, type 2
5. Fasting triglyceride ≥500 mg/dL at Screening, or patients with a history of lipid disorders taking unstable treatment dosage (eg, statins) within 3 months prior to screening
6. Any acute or chronic condition that, in the opinion of the Investigator, would limit the patient's ability to complete and/or participate in this trial
7. Blood amylase or lipase >3x ULN, history of acute or chronic pancreatitis, or history of symptomatic gallbladder disease at Screening
8. Serum creatinine ≥1.5 mg/dL (male patients) or ≥1.4 mg/dL (female patients), or estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at Screening
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) at Screening and pre-randomization
10. Severe cardiovascular diseases occurring within 6 months prior to screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PB-119 75ug	PB-119 75ug	PB-119 injection 75ug subcutaneously injected once-weekly for 12 weeks
PB-119 150ug	PB-119 150ug	PB-119 injection 150ug subcutaneously injected once-weekly for 12 weeks
PB-119 200ug	PB-119 200ug	PB-119 injection 200ug subcutaneously injected once-weekly for 12 weeks
placebo	placebo	placebo injection subcutaneously injected once-weekly for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change of glycosylated hemoglobin(HbA1c)	12 weeks	Change of HbA1c from baseline value to end of treatment

Secondary Outcome Measures

Name	Time	Method
2-hour postprandial glucose(2-h PPG)	4, 8, and 12 weeks	Changes of 2-hour postprandial glucose(2-h PPG) from baseline value at Weeks 4, 8, and 12.
Insulin	4, 8, and 12 weeks	Changes of insulin from baseline value at Weeks 4, 8, and 12
C-peptide	4, 8, and 12 weeks	Changes of C-peptide from baseline value at Weeks 4, 8, and 12
Self-monitoring of blood glucose (SMBG)	4, 8, and 12 weeks	Changes of mean profile and mean increments from baseline value of the 7-point SMBG
Percentage of patients achieving HbA1c <7%	12 weeks	Percentage of patients achieving HbA1c \<7% at Week 12
Percentage of patients achieving HbA1c ≤6.5%	12 weeks	Percentage of patients achieving HbA1c ≤6.5% at Week 12
HbA1c	2, 4, and 8 weeks	Changes of HbA1c from baseline value at Weeks 2, 4, and 8
Fasting plasma glucose(FPG)	2, 4, 8, and 12 weeks	Changes of fasting plasma glucose(FPG) from baseline value at Weeks 2, 4, 8, and 12.

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Peking, China