Clinical trial NCT03520972: Dose-finding of PB-119 Administered Subcutaneously Once-weekly Versus Placebo in Drug-naïve T2DM Subjects
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 in Drug-naïve Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: PegBio Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2018-05-11
Enrollment: 251
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: 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.

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

Primary outcomes:
measure: Change of glycosylated hemoglobin(HbA1c)
timeFrame: 12 weeks
Secondary outcomes:
measure: Percentage of patients achieving HbA1c <7%
timeFrame: 12 weeks
measure: Percentage of patients achieving HbA1c ≤6.5%
timeFrame: 12 weeks
measure: HbA1c
timeFrame: 2, 4, and 8 weeks
measure: Fasting plasma glucose(FPG)
timeFrame: 2, 4, 8, and 12 weeks
measure: 2-hour postprandial glucose(2-h PPG)
timeFrame: 4, 8, and 12 weeks
measure: Insulin
timeFrame: 4, 8, and 12 weeks
measure: C-peptide
timeFrame: 4, 8, and 12 weeks
measure: Self-monitoring of blood glucose (SMBG)
timeFrame: 4, 8, and 12 weeks
Other outcomes:
measure: Body mass index(BMI)
timeFrame: 2, 4, 8, and 12 weeks
measure: Waist and hip circumferences and waist-to-hip ratio
timeFrame: 12 weeks
measure: Blood pressure(both systolic and diastolic)
timeFrame: 2, 4, 8, and 12 weeks
measure: Blood lipid
timeFrame: 2, 4, 8, and 12 weeks
Locations:
city: Peking
country: China
facility: Peking University People's Hospital
Study officials:
affiliation: Peking University People's Hospital
name: Linong Ji, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.