A Pilot Study to Compare the Pharmacokinetics (PK) of Single Subcutaneous (SC) Injections of Vedolizumab Administered in Prefilled Syringe (PFS) Versus (vs) Prefilled Syringe in Autoinjector (PFS+AI) in Healthy Participants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03961295
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.1
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare PK of single dose of vedolizumab SC 108 milligram (mg) administered as PFS vs investigational device.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Vedolizumab SC	Phase 1

Detailed Description

The drug being tested in this study is called vedolizumab SC. The study will assess the PK, and variability of a vedolizumab SC in a PFS vs investigational device.

This study will include 2 different device delivery presentations in 2 treatment groups. Participants in each treatment group will be randomized to one of the three administration sites: Abdomen, thigh, or arm. The study will enroll approximately 24 participants, including 4 participants allocated to each administration site within each treatment group. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

• Group A: Vedolizumab SC PFS

• Group B: Vedolizumab SC Investigational Device

All participants will receive a single dose of study drug on Day 1.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 196 days. Participants will be contacted by telephone on Day 168 after their last dose of study drug for a follow-up assessment which will involve the progressive multifocal leukoencephalopathy (PML) questionnaire survey.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Open-Label, Randomized, Parallel Group Pilot Study to Compare the Pharmacokinetics of Single Subcutaneous Injections of Vedolizumab Administered in Prefilled Syringe Versus Prefilled Syringe in Autoinjector in Healthy Subjects
• Actual Study Start Date: Feb 22, 2018
• Actual Primary Completion Date: Jul 14, 2018
• Actual Study Completion Date: Aug 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A: Vedolizumab SC PFS Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Drug: Vedolizumab SC; Vedolizumab SC liquid.; Other Names: ENTYVIO, KYNTELES, MLN0002
Experimental: Group B: Vedolizumab SC Investigational Device Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.	Drug: Vedolizumab SC; Vedolizumab SC liquid.; Other Names: ENTYVIO, KYNTELES, MLN0002

Outcome Measures

Primary Outcome Measures

1. AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC [Day 1 pre-dose and at multiple time points (up to Day 127) post-dose]

2. AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC [Day 1 pre-dose and at multiple time points (up to Day 127) post-dose]

3. Cmax: Maximum Observed Serum Concentration for Vedolizumab SC [Day 1 pre-dose and at multiple time points (up to Day 127) post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Weighs greater than (>) 50 kilogram (kg) and less than (<) 90 kg and has a body mass index (BMI) from 18 to 28 kilogram per square meter (kg/m^2), inclusive, at the time of informed consent.

Exclusion Criteria:

1. Has received any investigational or approved biologic or biosimilar within 30 days or 5 half-lives, of Screening, whichever is longer.

2. Has had prior exposure to vedolizumab, or has hypersensitivity to vedolizumab or any of its components.

3. Has had previous exposure to approved or investigational anti-integrins (example, natalizumab, efalizumab, etrolizumab, AMG 181) or anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antibodies or rituximab.

4. Has 1 or more positive responses on the PML subjective symptom checklist at screening or before dosing on Day 1.

5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year before the Screening Visit or is unwilling to agree to abstain from alcohol for 7 days before Day -1 throughout confinement and for 48 hours before each clinic visit; and drugs throughout the study.

6. Has evidence of an active infection during the Screening Period.

7. Has received any live vaccinations within 30 days before Screening.

8. Has active or latent tuberculosis (TB) as evidenced by the following:

o A diagnostic TB test performed within 30 days of Screening or during the Screening

Period that is positive, defined as:

1. Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR

2. A TB skin test reaction greater than or equal to (>=) 5 millimeter (mm). NOTE: If participants have received Bacillus Calmette-Guerin (BCG) vaccine then a QuantiFERON TB Gold test should be performed instead of the TB skin test.

Note: Participants with documented previously treated TB with a negative QuantiFERON test can be included in the study.

1. Has poor peripheral venous access.

2. Is unable to attend all the study visits or comply with study procedures.

3. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including serum pheresis), or had a transfusion of any blood product within 45 days before Day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Dec 11, 2017
• Statistical Analysis Plan - May 24, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03961295
• Other Study ID Numbers: VedolizumabSC-1021; U1111-1205-7156
• First Posted: May 23, 2019
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Vedolizumab

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United states from 22 February 2018 to 28 August 2018.
Pre-assignment Detail	Healthy participants were enrolled in one of the two device presentation groups to receive vedolizumab subcutaneous (SC) 108 milligram (mg) using prefilled syringe (PFS) or using an investigational device. Primary objective was to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm).

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device	Total
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.2 (13.55)	33.6 (12.52)	35.4 (12.89)
Sex: Female, Male (Count of Participants)
Female	6 50%	6 50%	12 50%
Male	6 50%	6 50%	12 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%	1 8.3%	2 8.3%
Not Hispanic or Latino	11 91.7%	11 91.7%	22 91.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 8.3%	0 0%	1 4.2%
Asian	0 0%	1 8.3%	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 8.3%	3 25%	4 16.7%
White	10 83.3%	7 58.3%	17 70.8%
More than one race	0 0%	1 8.3%	1 4.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%	12 100%	24 100%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	71.35 (11.614)	69.26 (10.637)	70.30 (10.944)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	170.4 (10.08)	171.0 (7.94)	170.7 (8.88)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	24.558 (3.2381)	23.603 (2.7232)	24.080 (2.9663)

Outcome Measures

1. Primary Outcome

Title	AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC
Time Frame	Day 1 pre-dose and at multiple time points (up to Day 127) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set included all participants who received study drug and had at least 1 measurable serum concentration.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [microgram*day per milliliter(mcg*day/mL)]	433.4 (38.3)	560.3 (26.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments	Geometric least-squares means (LSMs) were calculated by exponentiating the LSMs derived from analysis of variance (ANCOVA) with weight as a covariate. Confidence intervals (CIs) were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.2984
	Confidence Interval	(2-Sided) 90%; 1.0786 to 1.5486
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC
Time Frame	Day 1 pre-dose and at multiple time points (up to Day 127) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who received study drug and had at least 1 measurable serum concentration.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [mcg*day/mL]	446.5 (36.2)	594.0 (23.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments	Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with weight as a covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.3274
	Confidence Interval	(2-Sided) 90%; 1.1147 to 1.5807
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Cmax: Maximum Observed Serum Concentration for Vedolizumab SC
Time Frame	Day 1 pre-dose and at multiple time points (up to Day 127) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who received study drug and had at least 1 measurable serum concentration.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (mcg/mL)]	13.70 (24.2)	16.53 (26.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments	Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with weight as a covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.1978
	Confidence Interval	(2-Sided) 90%; 1.0394 to 1.3804
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than Day 127
Adverse Event Reporting Description	At each visit the investigator had to assess any occurrence of adverse events. Participants may report adverse events occurring at any other time during the study. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Group A: Vedolizumab SC PFS		Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1.		Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
All Cause Mortality
	Group A: Vedolizumab SC PFS		Group B: Vedolizumab SC Investigational Device
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Group A: Vedolizumab SC PFS		Group B: Vedolizumab SC Investigational Device
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/12 (0%)
Infections and infestations
Pneumonia	1/12 (8.3%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Group A: Vedolizumab SC PFS		Group B: Vedolizumab SC Investigational Device
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/12 (75%)		6/12 (50%)
Gastrointestinal disorders
Abdominal pain	0/12 (0%)		1/12 (8.3%)
Dyspepsia	1/12 (8.3%)		0/12 (0%)
General disorders
Injection site pain	6/12 (50%)		3/12 (25%)
Injection site paraesthesia	1/12 (8.3%)		0/12 (0%)
Infections and infestations
Epididymitis	1/12 (8.3%)		0/12 (0%)
Pneumonia	0/12 (0%)		1/12 (8.3%)
Upper respiratory tract infection	2/12 (16.7%)		3/12 (25%)
Urinary tract infection	0/12 (0%)		1/12 (8.3%)
Vaginal infection	0/12 (0%)		1/12 (8.3%)
Viral infection	0/12 (0%)		1/12 (8.3%)
Vulvovaginal candidiasis	0/12 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/12 (0%)		1/12 (8.3%)
Nervous system disorders
Headache	1/12 (8.3%)		2/12 (16.7%)
Paraesthesia	1/12 (8.3%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)		0/12 (0%)
Sinus congestion	1/12 (8.3%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.