A 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: NCT03961308
• Collaborator: (none)
• Enrollment: 204
• Locations: 2
• Arms: 2
• Actual Duration (Months): 8.3
• Patients Per Site: 102
• Patients Per Site Per Month: 12.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the 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 compare the PK of a vedolizumab SC in a PFS to an 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 102 participants per group (a total of 204 participants), including 34 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: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Open-Label, Randomized, Parallel Group 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: Mar 12, 2018
• Actual Primary Completion Date: Oct 20, 2018
• Actual Study Completion Date: Nov 21, 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: MLN0002, ENTYVIO, KYNTELES
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: MLN0002, ENTYVIO, KYNTELES

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

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

3. 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.

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

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

6. 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-Gueri (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	Tempe	Arizona	United States	85283
2	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 - Jul 5, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03961308
• Other Study ID Numbers: VedolizumabSC-1022; U1111-1205-7175
• First Posted: May 23, 2019
• Last Update Posted: Nov 14, 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 12 March 2018 to 21 November 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 a 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 SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Period Title: Overall Study
STARTED	102	102
COMPLETED	100	100
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device	Total
Arm/Group Description	Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.	Total of all reporting groups
Overall Participants	102	102	204
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (11.96)	35.7 (13.96)	36.6 (12.99)
Sex: Female, Male (Count of Participants)
Female	42 41.2%	43 42.2%	85 41.7%
Male	60 58.8%	59 57.8%	119 58.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 7.8%	12 11.8%	20 9.8%
Not Hispanic or Latino	94 92.2%	90 88.2%	184 90.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 1%	3 2.9%	4 2%
Asian	4 3.9%	1 1%	5 2.5%
Black or African American	14 13.7%	11 10.8%	25 12.3%
White, Black or African American	3 2.9%	2 2%	5 2.5%
Native Hawaiian or Pacific Islander	1 1%	0 0%	1 0.5%
White	77 75.5%	82 80.4%	159 77.9%
White, American Indian or Alaska Native	1 1%	0 0%	1 0.5%
White, Asian	1 1%	2 2%	3 1.5%
White, Native Hawaiian or Pacific Islander	0 0%	1 1%	1 0.5%
Region of Enrollment (Count of Participants)
United States	102 100%	102 100%	204 100%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	73.93 (9.288)	71.61 (9.971)	72.77 (9.682)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	173.8 (8.76)	170.9 (9.78)	172.3 (9.37)
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	24.727 (2.3575)	24.580 (2.5635)	24.653 (2.4577)

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 one measurable serum concentration. The number of participants analyzed includes only those participants who had data available for this measure.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	97	97
Geometric Mean (Geometric Coefficient of Variation) [microgram*day per milliliter(mcg*day/mL)]	402.8 (38.3)	452.3 (39.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments
	Type of Statistical Test	Other
	Comments	Geometric least-squares means (LSMs) were calculated by exponentiating the LSMs derived from analysis of covariance (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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.0734
	Confidence Interval	(2-Sided) 90%; 0.9963 to 1.1565
	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 one measurable serum concentration. The number of participants analyzed includes only those participants who had data available for this measure.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	95	96
Geometric Mean (Geometric Coefficient of Variation) [mcg*day/mL]	424.3 (35.6)	479.8 (29.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments
	Type of Statistical Test	Other
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.0824
	Confidence Interval	(2-Sided) 90%; 1.0169 to 1.1521
	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 one measurable serum concentration. The number of participants analyzed includes only those participants who had data available for this measure.

Arm/Group Title	Group A: Vedolizumab SC PFS	Group B: Vedolizumab SC Investigational Device
Arm/Group Description	Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.	Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1.
Measure Participants	99	99
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (mcg/mL)]	12.60 (29.1)	13.66 (27.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device
	Comments
	Type of Statistical Test	Other
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMs
	Estimated Value	1.0465
	Confidence Interval	(2-Sided) 90%; 0.9935 to 1.1023
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the administration of the 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 AEs 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 SC 108 mg, injection, subcutaneously using a PFS, once on Day 1.		Vedolizumab SC 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	0/102 (0%)		0/102 (0%)
Serious Adverse Events
	Group A: Vedolizumab SC PFS		Group B: Vedolizumab SC Investigational Device
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/102 (1%)		0/102 (0%)
Gastrointestinal disorders
Abdominal pain	1/102 (1%)		0/102 (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	70/102 (68.6%)		72/102 (70.6%)
Cardiac disorders
Palpitations	0/102 (0%)		1/102 (1%)
Ear and labyrinth disorders
Cerumen impaction	1/102 (1%)		0/102 (0%)
Eye disorders
Eye pruritus	0/102 (0%)		1/102 (1%)
Gastrointestinal disorders
Abdominal discomfort	1/102 (1%)		0/102 (0%)
Abdominal distension	1/102 (1%)		1/102 (1%)
Abdominal pain	5/102 (4.9%)		0/102 (0%)
Abdominal pain lower	1/102 (1%)		0/102 (0%)
Anal fissure	0/102 (0%)		1/102 (1%)
Constipation	0/102 (0%)		1/102 (1%)
Diarrhoea	3/102 (2.9%)		3/102 (2.9%)
Flatulence	1/102 (1%)		0/102 (0%)
Haematochezia	0/102 (0%)		1/102 (1%)
Nausea	2/102 (2%)		3/102 (2.9%)
Proctalgia	0/102 (0%)		1/102 (1%)
Tooth impacted	1/102 (1%)		0/102 (0%)
Toothache	1/102 (1%)		0/102 (0%)
Vomiting	3/102 (2.9%)		2/102 (2%)
General disorders
Exercise tolerance decreased	0/102 (0%)		1/102 (1%)
Fatigue	1/102 (1%)		2/102 (2%)
Feeling drunk	1/102 (1%)		0/102 (0%)
Influenza like illness	1/102 (1%)		0/102 (0%)
Injection site erythema	1/102 (1%)		4/102 (3.9%)
Injection site induration	1/102 (1%)		1/102 (1%)
Injection site pain	45/102 (44.1%)		54/102 (52.9%)
Injection site pruritus	0/102 (0%)		1/102 (1%)
Nodule	0/102 (0%)		1/102 (1%)
Pain	0/102 (0%)		1/102 (1%)
Pyrexia	1/102 (1%)		1/102 (1%)
Vessel puncture site pain	1/102 (1%)		1/102 (1%)
Infections and infestations
Bacterial vulvovaginitis	0/102 (0%)		1/102 (1%)
Chlamydial infection	1/102 (1%)		0/102 (0%)
Conjunctivitis	1/102 (1%)		1/102 (1%)
Diverticulitis	0/102 (0%)		1/102 (1%)
Ear infection	0/102 (0%)		1/102 (1%)
Herpes zoster	1/102 (1%)		0/102 (0%)
Oral herpes	0/102 (0%)		1/102 (1%)
Otitis externa	0/102 (0%)		1/102 (1%)
Pharyngitis	0/102 (0%)		1/102 (1%)
Pharyngitis streptococcal	0/102 (0%)		1/102 (1%)
Pneumonia	0/102 (0%)		1/102 (1%)
Respiratory tract infection	0/102 (0%)		1/102 (1%)
Upper respiratory tract infection	1/102 (1%)		3/102 (2.9%)
Viral infection	0/102 (0%)		1/102 (1%)
Vulvovaginal candidiasis	0/102 (0%)		1/102 (1%)
Injury, poisoning and procedural complications
Laceration	1/102 (1%)		2/102 (2%)
Nerve injury	0/102 (0%)		1/102 (1%)
Radius fracture	1/102 (1%)		0/102 (0%)
Skin abrasion	1/102 (1%)		1/102 (1%)
Traumatic haematoma	0/102 (0%)		1/102 (1%)
Wound	1/102 (1%)		0/102 (0%)
Wrist fracture	0/102 (0%)		1/102 (1%)
Investigations
Neutrophil count decreased	0/102 (0%)		1/102 (1%)
Weight increased	0/102 (0%)		2/102 (2%)
Metabolism and nutrition disorders
Abnormal weight gain	1/102 (1%)		0/102 (0%)
Decreased appetite	0/102 (0%)		1/102 (1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/102 (1%)		0/102 (0%)
Arthritis	1/102 (1%)		0/102 (0%)
Back pain	3/102 (2.9%)		3/102 (2.9%)
Bursitis	0/102 (0%)		1/102 (1%)
Muscle spasms	0/102 (0%)		1/102 (1%)
Musculoskeletal chest pain	0/102 (0%)		1/102 (1%)
Musculoskeletal pain	2/102 (2%)		0/102 (0%)
Myalgia	1/102 (1%)		2/102 (2%)
Pain in extremity	0/102 (0%)		3/102 (2.9%)
Nervous system disorders
Clumsiness	0/102 (0%)		1/102 (1%)
Dizziness	2/102 (2%)		1/102 (1%)
Dysarthria	0/102 (0%)		1/102 (1%)
Dysgeusia	1/102 (1%)		0/102 (0%)
Fine motor skill dysfunction	0/102 (0%)		1/102 (1%)
Headache	8/102 (7.8%)		6/102 (5.9%)
Hypoaesthesia	1/102 (1%)		0/102 (0%)
Memory impairment	0/102 (0%)		1/102 (1%)
Migraine	0/102 (0%)		1/102 (1%)
Presyncope	0/102 (0%)		1/102 (1%)
Psychiatric disorders
Anxiety	1/102 (1%)		0/102 (0%)
Irritability	1/102 (1%)		1/102 (1%)
Renal and urinary disorders
Haematuria	2/102 (2%)		1/102 (1%)
Pollakiuria	1/102 (1%)		1/102 (1%)
Urinary retention	1/102 (1%)		0/102 (0%)
Reproductive system and breast disorders
Dysfunctional uterine bleeding	1/102 (1%)		0/102 (0%)
Vulvovaginal pruritus	1/102 (1%)		0/102 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/102 (1%)		0/102 (0%)
Dry throat	1/102 (1%)		0/102 (0%)
Dysphonia	1/102 (1%)		0/102 (0%)
Nasal congestion	1/102 (1%)		4/102 (3.9%)
Oropharyngeal pain	2/102 (2%)		1/102 (1%)
Paranasal sinus hypersecretion	0/102 (0%)		1/102 (1%)
Pharyngeal erythema	1/102 (1%)		0/102 (0%)
Rhinitis allergic	1/102 (1%)		0/102 (0%)
Rhinorrhoea	1/102 (1%)		0/102 (0%)
Throat irritation	0/102 (0%)		1/102 (1%)
Skin and subcutaneous tissue disorders
Alopecia	0/102 (0%)		1/102 (1%)
Dermatitis contact	1/102 (1%)		0/102 (0%)
Erythema	1/102 (1%)		0/102 (0%)
Rash pruritic	0/102 (0%)		1/102 (1%)
Vascular disorders
Hot flush	1/102 (1%)		0/102 (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.