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

NCT ID: NCT03520972

Last Updated: 2020-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 251 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-05
• Study Completion Date: 2019-07-29

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

PB-119 75ug

PB-119 injection 75ug subcutaneously injected once-weekly for 12 weeks

Group Type: EXPERIMENTAL

PB-119 75ug

Intervention Type: DRUG

60 eligible patients will be included in this group

PB-119 150ug

PB-119 injection 150ug subcutaneously injected once-weekly for 12 weeks

Group Type: EXPERIMENTAL

PB-119 150ug

Intervention Type: DRUG

60 eligible patients will be included in this group

PB-119 200ug

PB-119 injection 200ug subcutaneously injected once-weekly for 12 weeks

Group Type: EXPERIMENTAL

PB-119 200ug

Intervention Type: DRUG

60 eligible patients will be included in this group

placebo

placebo injection subcutaneously injected once-weekly for 12 weeks

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

60 eligible patients will be included in this group

Interventions

PB-119 75ug

60 eligible patients will be included in this group

Intervention Type: DRUG

PB-119 150ug

60 eligible patients will be included in this group

Intervention Type: DRUG

PB-119 200ug

60 eligible patients will be included in this group

Intervention Type: DRUG

placebo

60 eligible patients will be included in this group

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tigermed Consulting Co., Ltd

INDUSTRY

Sponsor Role: collaborator

PegBio Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linong Ji, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

Peking University People's Hospital

Beijing, , China

Countries

China

References

Ji L, Du Y, Xu M, Zhou X, Mo Z, Ma J, Li J, Li Y, Lin J, Wang Y, Yang J, Song W, Jin H, Pang S, Liu H, Li P, Liu J, Yao M, Li W, Jiang X, Shen F, Geng H, Zhou H, Ran J, Lei M, Du Y, Ye S, Guan Q, Lv W, Tan H, Chen T, Yang J, Qin G, Li S, Chen L. Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study. Diabetologia. 2021 May;64(5):1066-1078. doi: 10.1007/s00125-021-05392-9. Epub 2021 Mar 9.

Reference Type: DERIVED

PMID: 33687487 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30957581 (View on PubMed)

Other Identifiers

PB119201

Identifier Type: -

Identifier Source: org_study_id