A Study to Compare the Pharmacokinetics of JHL1149 and Bevacizumab (Avastin) in Healthy Male Volunteers

A Phase I, Double-blind, Randomized, Parallel-group, Single-dose, Three-Arm Study to Compare the Pharmacokinetics and to Evaluate the Tolerability, Safety and Immunogenicity of JHL1149 and Bevacizumab (Avastin) in Healthy Male Volunteers

This is a Phase I, Double-blind, Randomized, Parallel-group, Single-dose, Three-Arm Study to Compare the Pharmacokinetics and to Evaluate the Tolerability, Safety and Immunogenicity of JHL1149 and Bevacizumab (Avastin) Sourced from the European Union (EU) and the Union States (US) in Healthy Male Volunteers

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects
• Intervention / Treatment: Biological: JHL1149; Biological: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1336
    • MHAT Lyulin EAD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male volunteers,
2. Age range of 21-55 years (inclusive).
3. BMI range of 18.0-30.0 kg/m2 (inclusive) and a total body weight >50 kg.
4. Medically healthy subjects with normal organ functions and laboratory values
5. Subjects must be willing to use adequate contraception and not donate sperm from admission to clinical research center until 6 months post dosing.
6. All intermittent medications including over the counter, herbal and nutriceuticals, must be stopped at least 14 days prior to admission to the clinical research center.
7. Ability and willingness to abstain from alcohol 48hrs prior to admission to the clinical research center, and throughout the dosing and evaluation period.
8. No significant medical history per the PI judgment.
9. ECGs (via 12 lead) showing normalized cumulative sum (NCS) findings per PI judgment
10. Ability to provide informed consent for the study.

Exclusion Criteria:

1. Previous treatment with an anti-vascular endothelial growth factor (VEGF) antibody or any other antibody or protein targeting the VEGF receptor or treatment with an immunobiological drug during the last three months.
2. Previous history of cancer other than adequately treated basal cell or squamous cell carcinoma of the skin.
3. Received blood transfusions and blood donation within 3 months before screening date.
4. Resting blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg.
5. Any other severe physical incapacity.
6. Positive serological test for hepatitis B surface antigen or positive antibody for hepatitis C virus or positive antibody for human immunodeficiency virus (type 1 and 2).
7. Tuberculosis (TB) or an acute systemic infection; demonstrated by positive QuantiFERON-TB and/or Chest radiograph conducted up to 3 months prior or during the screening visit.
8. Major surgery planned for the study duration or cases with major surgery in the past 28 days before screening.
9. History of relevant drug and/or food related allergies.
10. History of or known hypersensitivity to bevacizumab or other recombinant human or humanized antibodies or inactive ingredients.
11. History of alcohol and or drug abuse/addiction.
12. Positive alcohol breath test and drug screen for opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines.
13. Strenuous exercise 96 hrs prior to admission to the clinical research center.
14. Any significant or acute illness within 30 days prior to the expected first dose of study drug.
15. Unsuitable veins for infusion and/or venepuncture.
16. History of bleeding disorders, thromboembolic conditions, gastrointestinal perforations or any fistulae, orthostatic hypotension, fainting spells, blackouts for any reasons; as well as presence of a non-healing wound or fracture.
17. Participation in another clinical study where the investigational drug was received within < 5 x half-lives of the drug (120 days prior to screening).
18. Any condition or displayed behaviour that the investigator in their best clinical judgement believes could be detrimental the subject's participation in the study or result in unfavourable outcomes for the subject or study (eg. Clear signs that the patient is withholding information on their substance use/abuse status).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: JHL1149	Biological: JHL1149; Each patient may receive single dose of JHL1149 1mg/kg by intravenous infusion
ACTIVE_COMPARATOR: US-sourced-Avastin™	Biological: Bevacizumab; Each patient may receive single dose of Avastin 1mg/kg by intravenous infusion
ACTIVE_COMPARATOR: EU-sourced Avastin™	Biological: Bevacizumab; Each patient may receive single dose of Avastin 1mg/kg by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf	area under the concentration-time curve from time zero to infinity (AUC0-inf)	up to 71 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Area under the serum concentration-time curve from time 0 to last quantifiable concentration (AUClast).	up to 71 days
Cmax	Maximum serum concentration just prior to end of infusion (Cmax)	up to 71 days

Collaborators and Investigators

• Sponsor: JHL Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 24, 2018
• Primary Completion (ACTUAL): September 17, 2018
• Study Completion (ACTUAL): December 13, 2019

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (ACTUAL): July 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 5, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: JHL-CLIN-1149-01

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