Clinical Trial for Comparison of RPH-001 to Avastin®

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2017-001634-26-Outside-EU/EEA
• Date of registration: 07/06/2017
• Prospective Registration: Yes
• Primary sponsor: TRPHARM
• Public title: Clinical Trial for Comparison of RPH-001 to Avastin®
• Scientific title: Phase I, Double Blind, Randomized, Parallel-Arm, Single-Dose, Pharmacokinetic and Safety Study of Bevacizumab-biosimilar (RPH-001) Compared to Bevacizumab-innovator (Avastin®, Roche) in Healthy Male Volunteers
• Target sample size: 60
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001634-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Turkey

Contacts

• Name: MEDICAL MANAGER
• Affiliation: MONITOR CRO

• Name: MEDICAL MANAGER
• Affiliation: MONITOR CRO

Key inclusion & exclusion criteria

Inclusion criteria:
I-1. Healthy male subjects aged 18 to 55 years inclusive.
I-2. Adult healthy male subjects between 18.0 and 30.0 kg/m2 body mass index (inclusive) and body weight = 60 kg and = 100 kg (inclusive).
I-3. Certified as healthy by a comprehensive clinical assessment (detailed medical history [hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 3 weeks prior start of the trial, registration of life style and habits such as consumption of alcohol, nicotine, coffee, tea, coke, special diet, drug abuse]) and complete physical examination (general state and abnormal findings per system: endocrine/metabolic, allergies, drug sensitivities, head, neck, eyes, ears, nose, throat, cardiovascular, respiratory, gastrointestinal, hepatic/biliary, urogenital, musculoskeletal, Lymph nodes, skin, and neurological/psychiatric).
I-4. Normal vital signs after 10 minutes resting in supine position:
• 90 mmHg < systolic blood pressure (SBP) <140 mmHg
• 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
• 40 bpm < heart rate (HR) <100 bpm
I-5. Normal standard 12-lead electrocardiogram (ECG) after 10 minutes resting in supine position in the following ranges; 120 msI-6. Subjects whose clinical laboratory test results are normal, or where outside the reference range is judged as not clinically relevant by the Investigator
I-7. Having given written informed consent prior to undertaking any study-related procedure.
I-8. Negative Quantiferon TB gold test.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
E-1. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
E-2. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
E-3. Blood or plasma donation, or transfusion with any volume, within 3 months before inclusion.
E-4. Symptomatic hypotension, irrespective of the decrease in blood pressure.
E-5. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
E-6. Major surgery including appendectomy with in last 12 weeks.
E-7. History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day).
E-8. Current smoker of more than 5 cigarettes or equivalent per day during the study and unable to completely stop smoking during the hospitalization.
E-9. Excessive consumption of beverages containing xanthine bases such as tea, coffee, coke etc. (more than 500 mg xanthine per day).
E-10. Medication with drugs known to alter organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within the last 2 months.
E-11. Any medication (including St John’s Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.
E-12. Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
E-13. Any subject in the exclusion period of a previous study according to applicable regulations.
E-14. Any subject who cannot be contacted in case of emergency.
E-15. Any subject who is the Investigator or any Sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study.
E-16. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
E-17. Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
E-18. Positive alcohol test at screening or baseline visits
E-19. Any contraindications to biological molecules according to the applicable labeling.
E-20. Vegetarian diet
E-21. Participation in another clinical trial at same time or within the preceding 3 months (calculated from the date of the final examination of the previous study), except for previous BE trials in which case 8 weeks are sufficient.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Non-Small Cell Lung Cancer
MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Code: RPH-001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: bevacizumab biosimilar
Current Sponsor code: RPH-001
Other descriptive name: BEVACIZUMAB BIOSIMILAR
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Trade Name: Avastin®
Product Name: Avastin®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 100 days after the administration of IMP

Main Objective: To evaluate and compare pharmacokinetic profile of RPH-001 (TRPHARM) versus EU sourced Avastin® (Roche), after single IV administration at 5 mg/kg fixed dose.

Secondary Objective: To assess safety (including immunogenicity) and tolerability of test and reference products.

Primary end point(s): Primary Pharmacokinetic Endpoints: Cmax, AUC(o-t), and AUC(0-8).

Secondary Outcome(s)

Secondary end point(s): Secondary Pharmacokinetic Endpoints: tmax, t1/2, ?z, CL, Vss
Safety Endpoints: Physical examinations, laboratory tests, vital signs, electrocardiogram (ECG) evaluations, adverse events (AEs) and serious adverse events (SAEs).

Timepoint(s) of evaluation of this end point: 100 days after the administration of IMP

Secondary ID(s)

RPH001BEV01

Source(s) of Monetary Support

TRPHARM