Safety and PK of HM10460A (HNK460) in Healthy Adult Japanese and Caucasian Subjects

A Randomized, Double-Blind, Placebo- and Active-Controlled, Escalating Single-Dose Study to Evaluate the Safety, Tolerability, and PK of HM10460A (HNK460) When Administered Subcutaneously to Healthy Adult Japanese and Caucasian Subjects.

Study Design

• Randomized, double-blind, placebo-controlled, escalating single-dose design.
• Six ascending dose cohorts
• In each cohorts, subjects will be randomized to receive a single dose of HM10460A, placebo (negative control), or Neulasta® (positive control).
• Primary Objective
• to assess the safety and tolerability of single escalating subcutaneous doses of HM10460A in healthy adult Japanese and Caucasian subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: HM10460A or placebo or Neulasta

Detailed Description

Secondary objectives:

• to assess the pharmacokinetics (PK) of a single subcutaneous dose of HM10460A.
• to compare the PK of HM10460A in Japanese and Caucasian subjects.
• to assess the relationship between the serum concentration of HM10460A and absolute neutrophil count (ANC).
• to assess the relationship between the serum concentration of HM10460A and CD34+ cell counts in the blood.
• To assess the immunogenicity potential of HM10460A by measuring binding antibodies (bAb) and neutralizing antibodies (nAb) to HM10460A and native G-CSF following a single subcutaneous dose of HM10460A.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • California, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI of 18 - 29.9 kg/m2
• have not used tobacco or nicotine containing products for at least 3 months prior to dosing
• be able to remain abstinent throughout the study.

Exclusion Criteria:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• positive urine drug/alcohol testing
• Positive for HIV, HBsAg, HCV ab
• History of anaphylactic reaction to medicine or environmental exposure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 1.1 mcg/kg of HM10460A, placebo, or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF
Experimental: Cohort 2; 3.3 mcg/kg HM10460A, placebo or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF
Experimental: Cohort 3; 10 mcg/kg of HM10460A, placebo, or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF
Experimental: Cohort 4; 30 mcg/kg of HM10460A, placebo, or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF
Experimental: Cohort 5; 90 mcg/kg or HM10460A, placebo, or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF
Experimental: Cohort 6; 270 mcg/kg of HM10460A, placebo, or Neulasta	Drug: HM10460A or placebo or Neulasta; Single SC injection of the appropriate dose of drug ranging from 1.1 mcg/kg to 270 mcg/kg.; Other Names: LAPS-G-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety data, including physical examinations (to include injection site reactions and splenic evaluations), laboratory evaluations, ECGs, vital signs assessments, and adverse effects (AEs).	Time points where appropriate.
Samples for immunogenicity	Days -1, 15, 22, and 42.

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameters measured from Serum and Urine samples.	Serum samples: pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hrs, Days 4, 5, 6, 7, 11, 15, and 22. / Urine Samples: 0 - 6, 6 - 12, 12 - 24, 24 - 36, and 36 - 48 hours post-dose.
Calculation of ANC and CD34+ cell counts.	pre-dose, 24 and 48 hours post-dose, Days 4, 5, 6, 7, 11, 15, and 22.

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited
• Investigators: Principal Investigator: Hanmi Clinical, California

Publications and helpful links

General Publications

• Jeon Y, Lee N, Baek S, Choi J, Jhee S, Lee H. A Randomized, Double-Blind, Placebo- and Active-Controlled, Escalating Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Profiles of Subcutaneous Eflapegrastim in Healthy Japanese and Caucasian Subjects. Drugs R D. 2022 Mar;22(1):71-87. doi: 10.1007/s40268-021-00379-8. Epub 2022 Jan 6.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: December 21, 2009
• First Submitted That Met QC Criteria: December 21, 2009
• First Posted (Estimate): December 23, 2009

Study Record Updates

• Last Update Posted (Estimate): February 7, 2014
• Last Update Submitted That Met QC Criteria: February 5, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 08-HM10460A-101