A Phase 1, Double-blind, Randomized, Placebo-controlled, Single- and Multiple-dose Escalating Study

A Phase 1, Double-blind, Randomized, Placebo-controlled, Single- and Multiple-dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PB-718 Following Subcutaneous Administration in Healthy Subjects

This will be a randomized, double-blind, placebo-controlled, single- and multiple SC dose escalating study conducted in 2 parts.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: PB 718

Detailed Description

A Phase 1, double-blind, randomized, placebo-controlled, single and multiple-dose escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB-718 following subcutaneous administration in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
2. Males or females, of any race, between 18 and 55 years of age, inclusive.
3. Male subjects will weigh at least 50 kg, and female subjects will weigh at least 45 kg. Body mass index between 20.0 and 30.0 kg/m2 (Part A) or 25.0 to 50.0 kg/m2 (Part B), inclusive.
4. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and Check-in/predose as assessed by the Investigator (or designee).

Exclusion Criteria:

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular or other heart disease, gastrointestinal, urinary/prostatic, neurological, respiratory, endocrine, or psychiatric disorder, or glaucoma, as determined by the Investigator (or designee).
2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
3. Liver disease or liver injury, as indicated by abnormal liver function tests (e.g. serum bilirubin, direct bilirubin, ALT, AST, γ-GT, or ALK exceeding the ULN) at Screening or Baseline which may be repeated for confirmation per the Investigators discretion at Screening and Check-in.
4. History of multiple endocrine neoplasia type 2 or an abnormal thyroid function test (thyroid stimulating hormone, triiodothyronine, thyroxine) at Screening or Baseline.
5. Fasting plasma glucose greater than ≥126 mg/dL at Baseline.
6. Hemoglobin A1c value >6.5%
7. History of chronic or acute pancreatitis, or amylase or lipase exceeding 2 × ULN at Screening or Baseline. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A1; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group A2; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group A3; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group A4; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group A5; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group A6; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group B1; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group B2; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group B3; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group
EXPERIMENTAL: Group B4; PB-718 vs placebo	Drug: Placebo; matching placebo; Drug: PB 718; dose in the next group will be determined following a review of data from the previous group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence, causality, and severity of AE. The condition of each subject will be monitored from the time of signing the ICF to Final Discharge from the study. Subjects will be observed for any signs or symptoms and asked about their condition by open questioning, such as "How have you been feeling since you were last asked?", at least once each day while resident at the study site and at each study visit. Subjects will also be encouraged to spontaneously report AEs occurring at any other time during the study.	From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile	AUC (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) from time zero to the time of the last quantifiable concentration (AUC0-tlast)	From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks.
Pharmacokinetic (PK) profile	Cmax (maximum observed plasma concentration)	From Group A1 until Group B4.The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks.
Pharmacokinetic (PK) profile	Tmax (time of the maximum observed plasma concentration)	From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks.
Pharmacokinetic (PK) profile	terminal disposition phase rate constant (λz)	From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks.

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Collaborators: Covance
• Investigators: Principal Investigator: Hugh Coleman, MD, Daytona Beach CRU

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 29, 2020
• Primary Completion (ACTUAL): May 18, 2022
• Study Completion (ACTUAL): August 12, 2022

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 19, 2021
• First Posted (ACTUAL): August 25, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: PB718-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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