Vedolizumab Subcutaneous (SC) Versus Intravenous (IV) in Ulcerative Colitis or Crohn's Disease

NCT02913508 | Withdrawn Phase 2 DMC

• 3 other identifiers: MLN0002SC_2012013-003030-32U1111-1146-5451
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the bioavailability and pharmacokinetics (PK) of multiple doses of vedolizumab subcutaneous (SC) compared to vedolizumab intravenous (IV).

Conditions

Ulcerative Colitis; Crohn's Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• Average Concentration of Vedolizumab Over the Dosing Interval at Steady-State (Cavg, ss)

  Cavg, ss is defined as the average concentration over the dosing interval at steady-state, calculated as area under the serum concentration-time curve over the dosing interval at steady-state(AUCss)/Tau, where Tau is the dosing interval.

  Week 0 up to Week 22

• Average Concentration of Vedolizumab Over the Dosing Interval from Week 0 to Week 6 (Cavg[wk0-6])

  Area under the serum concentration-time curve from Week 0 to Week 6, calculated using the linear trapezoidal rule.

  Week 0 to Week 6

Secondary Outcomes (4)

• Percentage of Participants with Positive Human Antihuman Antibody (HAHA) During the Study

  Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38

• Percentage of Participants with Positive Neutralizing Human Antihuman Antibody (HAHA) During the Study

  Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38

• Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 6

  Week 6

• Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 22

  Week 22

Study Arms (5)

Vedolizumab 300 mg IV Q8W

EXPERIMENTAL

Vedolizumab 300 mg, intravenously, at Weeks 0 and 2, and then every 8 weeks (Q8W) (Weeks 6 and 14).

Drug: Vedolizumab intravenous injection

Vedolizumab 300 mg IV / 160 mg SC Q3W

EXPERIMENTAL

Vedolizumab 300 mg, intravenously, at Weeks 0 and 2, then vedolizumab 160 mg, subcutaneously (SC), every 3 weeks (Q3W) (Weeks 6, 9, 12, 15 and 18).

Drug: Vedolizumab intravenous injection; Drug: Vedolizumab subcutaneous injection

Vedolizumab 300 mg IV / 108 mg SC Q2W

EXPERIMENTAL

Vedolizumab 300 mg, intravenously, at Weeks 0 and 2, then vedolizumab 108 mg, subcutaneously, every 2 weeks (Q2W) (Weeks 6, 8, 10, 12, 14, 16, 18 and 20).

Drug: Vedolizumab intravenous injection; Drug: Vedolizumab subcutaneous injection

Vedolizumab 480 mg SC / 160 mg SC Q3W

EXPERIMENTAL

Vedolizumab 480 mg, subcutaneously, at Weeks 0 and 2, then vedolizumab 160 mg, subcutaneously, every 3 weeks (Weeks 6, 9, 12, 15 and 18).

Drug: Vedolizumab subcutaneous injection

Vedolizumab 324 mg SC / 108 mg SC Q2W

EXPERIMENTAL

Vedolizumab 324 mg, subcutaneously, at Weeks 0 and 2, then vedolizumab 108 mg, subcutaneously, every 2 weeks (Weeks 6, 8, 10, 12, 14, 16, 18 and 20).

Drug: Vedolizumab subcutaneous injection

Interventions

Vedolizumab intravenous injection DRUG

Vedolizumab intravenous injection

Also known as: MLN0002, Entyvio

Vedolizumab 300 mg IV / 108 mg SC Q2W; Vedolizumab 300 mg IV / 160 mg SC Q3W; Vedolizumab 300 mg IV Q8W

Vedolizumab subcutaneous injection DRUG

Vedolizumab subcutaneous injection

Also known as: MLN0002SC

Vedolizumab 300 mg IV / 108 mg SC Q2W; Vedolizumab 300 mg IV / 160 mg SC Q3W; Vedolizumab 324 mg SC / 108 mg SC Q2W; Vedolizumab 480 mg SC / 160 mg SC Q3W

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.
• Is aged 18 to 80 years, inclusive.
• The male or female participant is voluntarily able to give informed consent.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
• Has a diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report.
• Has moderately to severely active UC as determined by a partial Mayo score of 3 to 9 within 7 days prior to the first dose of study drug.
• Has evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
• Participants with extensive colitis or pancolitis of \>8 years duration or left-sided colitis of \>12 years duration must have documented evidence that a surveillance colonoscopy with random and targeted biopsies was performed within 18 months of the initial screening visit (may be performed during screening).
• Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age \>50 years, or other known risk factor for colorectal cancer must be up-to-date on colorectal cancer surveillance (may be performed during screening).
• Participants may be receiving a therapeutic dose of the following drugs:
• Oral or topical (rectal) 5-aminosalicylate (5-ASA) compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization;
• Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a dose ≤9 mg/day or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to randomization if corticosteroids have just been initiated, or for the 2 weeks immediately prior to randomization if corticosteroids are being tapered;
• Topical (rectal) corticosteroid enemas/suppositories;

You may not qualify if:

• Evidence of abdominal abscess at the initial Screening Visit.
• Extensive colonic resection, subtotal or total colectomy.
• History of \>3 small bowel resections or diagnosis of short bowel syndrome.
• Have received tube feeding, defined formula diets, or parenteral alimentation within 21 days prior to the administration of the first dose of study drug.
• Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
• Within 30 days prior to randomization, have received any of the following for the treatment of underlying disease: a) Any investigational or approved nonbiologic therapy for UC or CD (eg, cyclosporine, thalidomide) other than those specified in the protocol.
• Within 60 days prior to randomization, have received any of the following:
• Infliximab,
• Certolizumabpegol,
• Adalimumab,
• Golimumab,
• Any other investigational or approved biological agent, other than local injections for non IBD conditions (eg, intra-ocular injections for the treatment of wet macular degeneration).
• Evidence of or treatment for clostridium difficile infection or other intestinal pathogen within 28 days prior to randomization.
• Currently require or are anticipated to require major surgical intervention during the study.
• History or evidence of adenomatous colonic polyps that have not been removed.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2016
• First Posted: September 23, 2016
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 23, 2016

Record last verified: 2016-09