To Demonstrate Similarity of Pharmacokinetics and Evaluate Safety of CT-P16, EU-Approved Avastin and US-licensed Avastin

• Sponsor: Celltrion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03247673
• Collaborator: (none)
• Enrollment: 141
• Locations: 3
• Arms: 3
• Actual Duration (Months): 5.4
• Patients Per Site: 47
• Patients Per Site Per Month: 8.8

Study Details

Study Description

Brief Summary

This study is a Phase 1 Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to compare the PK, safety and immunogenicity of the proposed biosimilar test product CT-P16 with EU-approved Avastin and US-licensed Avastin after a single IV infusion of 5mg/kg of each product to healthy male subjects

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: CT-P16; Drug: EU-approved Avastin; Drug: US-licensed Avastin	Phase 1

Detailed Description

This study is a double-blind, three-arm, parallel group, single-dose study. A total of 141 subjects will be enrolled; 47 subjects in each of the 3 arms of the clinical study. In each arm, all subjects will receive a single dose (5 mg/kg) of either CT-P16, EU-approved Avastin, or US-licensed Avastin by intravenous (IV) infusion for 90 min (±5 min) on Day 1 followed by 15 weeks during which the PK, safety, and immunogenicity measurements will be made. The randomization will be stratified by body weight and site.

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics and Safety of Three Formulations of Bevacizumab (CT-P16, EU-approved Avastin and US-licensed Avastin) in Healthy Male Subjects
• Actual Study Start Date: Aug 7, 2017
• Actual Primary Completion Date: Dec 22, 2017
• Actual Study Completion Date: Jan 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CT-P16 CT-P16 will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: CT-P16; CT-P16 is a biosimilar product for Avastin; Other Names: bevacizumab
Active Comparator: EU-approved Avastin EU-approved Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: EU-approved Avastin; EU-approved Avastin; Other Names: bevacizumab
Active Comparator: US-licensed Avastin US-licensed Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: US-licensed Avastin; US-licensed Avastin; Other Names: bevacizumab

Outcome Measures

Primary Outcome Measures

1. AUC0-inf [pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI]

   Area under the concentration-time curve from time zero to infinity

2. Cmax [pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI]

   Maximum Serum Concentration (Cmax)

3. AUC0-last [pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI]

   Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration

Secondary Outcome Measures

1. Additional Pharmacokinetics (Time to Cmax) [pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI]

   To assess the additional PK of study drugs (Time to Cmax)

2. Number of Participants With Anti-Drug Antibody Positive [up to 15 weeks]

   number of participants with anti-drug antibody positive at post-dose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male subjects between the ages of 19 and 55 years, both inclusive

• Body Mass Index (BMI) between 18.0 and 29.9 kg/m2 (both inclusive) and a body weight ≥ 50 kg

Exclusion Criteria:

• Subject is a female.

• Clinically significant allergic reactions, hypersensitivity

• A disease classed as significant by the Investigator

• Non-healing wound, ulcer, bone fracture, a major surgical procedure, significant traumatic injury

• Any malignancy

• Undergone treatment with an investigational drug or participated in another clinical trial

• Plans to father a child or donates sperms

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Inje University Busan Paik Hospital	Busan		Korea, Republic of
2	Inha University Hospital	Incheon		Korea, Republic of
3	Seoul St.Mary's hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Celltrion

Investigators

• Study Director: Sung Young Lee, Celltrion

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 29, 2018
• Study Protocol - Jun 7, 2017

More Information

Additional Information:

• Celltrion, Inc. homepage

Publications

None provided.

• Responsible Party: Celltrion
• ClinicalTrials.gov Identifier: NCT03247673
• Other Study ID Numbers: CT-P16 1.1
• First Posted: Aug 14, 2017
• Last Update Posted: Mar 26, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celltrion: safety; Pharmacokinetics; Immunogenicity
• Additional relevant MeSH terms: Bevacizumab

Study Results

Participant Flow

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Period Title: Overall Study
STARTED	46	47	48
COMPLETED	45	47	44
NOT COMPLETED	1	0	4

Baseline Characteristics

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin	Total
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin	Total of all reporting groups
Overall Participants	46	47	48	141
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (8.69)	28.4 (7.59)	26.5 (6.28)	27.8 (7.57)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	46 100%	47 100%	48 100%	141 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	46 100%	47 100%	48 100%	141 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
South Korea	46 100%	47 100%	48 100%	141 100%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.93 (9.073)	71.01 (9.417)	69.54 (8.141)	70.16 (8.845)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.89 (2.310)	23.20 (2.492)	23.17 (2.303)	23.09 (2.357)

Outcome Measures

1. Primary Outcome

Title	AUC0-inf
Description	Area under the concentration-time curve from time zero to infinity
Time Frame	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Measure Participants	46	47	48
Mean (Standard Deviation) [h*ug/mL]	42034.90 (6070.668)	40413.44 (5012.778)	43017.95 (5782.951)

2. Primary Outcome

Title	Cmax
Description	Maximum Serum Concentration (Cmax)
Time Frame	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Measure Participants	46	47	48
Mean (Standard Deviation) [ug/mL]	117.22 (17.756)	114.06 (15.391)	113.09 (17.402)

3. Primary Outcome

Title	AUC0-last
Description	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration
Time Frame	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Measure Participants	46	47	48
Mean (Standard Deviation) [h*ug/mL]	41142.81 (5694.184)	39411.98 (4649.319)	41804.05 (5463.814)

4. Secondary Outcome

Title	Additional Pharmacokinetics (Time to Cmax)
Description	To assess the additional PK of study drugs (Time to Cmax)
Time Frame	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Measure Participants	46	47	48
Median (Full Range) [h]	2.5	2.5	2.5

5. Secondary Outcome

Title	Number of Participants With Anti-Drug Antibody Positive
Description	number of participants with anti-drug antibody positive at post-dose
Time Frame	up to 15 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	CT-P16	EU-approved Avastin	US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin	EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin	US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
Measure Participants	46	47	48
Count of Participants [Participants]	2 4.3%	2 4.3%	3 6.3%

Adverse Events

Time Frame	up to 15 weeks
Arm/Group Title	CT-P16		EU-approved Avastin		US-licensed Avastin
Arm/Group Description	CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects CT-P16: CT-P16 is a biosimilar product for Avastin		EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects EU-approved Avastin: EU-approved Avastin		US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects US-licensed Avastin: US-licensed Avastin
All Cause Mortality
	CT-P16		EU-approved Avastin		US-licensed Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/47 (0%)		0/48 (0%)
Serious Adverse Events
	CT-P16		EU-approved Avastin		US-licensed Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/47 (0%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	CT-P16		EU-approved Avastin		US-licensed Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/46 (32.6%)		22/47 (46.8%)		17/48 (35.4%)
Gastrointestinal disorders
Diarrhea	3/46 (6.5%)		6/47 (12.8%)		4/48 (8.3%)
Infections and infestations
Nasopharyngitis	4/46 (8.7%)		1/47 (2.1%)		6/48 (12.5%)
Injury, poisoning and procedural complications
Infusion-related reaction	2/46 (4.3%)		2/47 (4.3%)		4/48 (8.3%)
Investigations
Blood creatine phosphokinase increased	3/46 (6.5%)		5/47 (10.6%)		4/48 (8.3%)
C-reactive protein increased	2/46 (4.3%)		5/47 (10.6%)		4/48 (8.3%)
Troponin I increased	1/46 (2.2%)		3/47 (6.4%)		0/48 (0%)
White blood cell count decreased	1/46 (2.2%)		0/47 (0%)		3/48 (6.3%)
Nervous system disorders
Headache	1/46 (2.2%)		2/47 (4.3%)		3/48 (6.3%)

Limitations/Caveats

Subject with unreliable PK parameter results were excluded from summary. Only treatment-emergent adverse events were summarized.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.