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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: HM10460A or placebo or Neulasta

• Registration Number: NCT01037543
• Lead Sponsor: Hanmi Pharmaceutical Company Limited

Brief Summary

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.

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 Timeline

• Study Start: 2009-11
• Study First Submitted: 2009-12-21
• Study First Submitted QC: 2009-12-21
• Study First Posted: 2009-12-23
• Primary Completion: 2011-02
• Study Completion: 2011-04
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-05
• Last Update Posted: 2014-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 4	HM10460A or placebo or Neulasta	30 mcg/kg of HM10460A, placebo, or Neulasta
Cohort 3	HM10460A or placebo or Neulasta	10 mcg/kg of HM10460A, placebo, or Neulasta
Cohort 1	HM10460A or placebo or Neulasta	1.1 mcg/kg of HM10460A, placebo, or Neulasta
Cohort 2	HM10460A or placebo or Neulasta	3.3 mcg/kg HM10460A, placebo or Neulasta
Cohort 5	HM10460A or placebo or Neulasta	90 mcg/kg or HM10460A, placebo, or Neulasta
Cohort 6	HM10460A or placebo or Neulasta	270 mcg/kg of HM10460A, placebo, or Neulasta

Primary Outcome Measures

Name	Time	Method
Samples for immunogenicity	Days -1, 15, 22, and 42.
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.

Secondary Outcome Measures

Name	Time	Method
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.