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Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)

Primary Purpose

Ulcerative Colitis

Status

Terminated

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

MTX 12.5

MTX 25

Adalimumab

About this trial

This is an interventional treatment trial for Ulcerative Colitis focused on measuring Moderately to severely active Ulcerative Colitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
Diagnosis of UC confirmed by established criteria, regardless of disease duration.
Moderate to severely active UC, defined by a modified Mayo Score ≥6, with confirmed endoscopic activity by central reader (Mayo endoscopic subscore ≥2).
Require initiation with adalimumab for induction of remission.
Ability of subject to swallow study drug capsules.
Ability of subject to participate fully in all aspects of this clinical trial.
Written informed consent must be obtained and documented.

Exclusion Criteria:

Prior treatment with a TNF antagonist or biological therapy.
Prior treatment with MTX.
Disease limited to the rectum (proctitis).
Documented presence of antibodies against adalimumab.
Contraindication for anti-TNF or MTX therapy.
Contraindication for endoscopy.
Ostomy.
Planned surgery.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

MTX 12.5

MTX 25 mg

Placebo

Arm Description

Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab

Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab

Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab

Outcomes

Primary Outcome Measures

Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups

The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance

Secondary Outcome Measures

Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.

UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration). The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance

Full Information

NCT ID

NCT01716039

First Posted

October 15, 2012

Last Updated

June 1, 2021

Sponsor

Alimentiv Inc.

Collaborators

Abbott

1. Study Identification

Unique Protocol Identification Number

NCT01716039

Brief Title

Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)

Official Title

A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Terminated

Why Stopped

Unable to achieve recruitment target.

Study Start Date

June 2013 (undefined)

Primary Completion Date

July 18, 2016 (Actual)

Study Completion Date

July 18, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alimentiv Inc.

Collaborators

Abbott

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.

Detailed Description

Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ulcerative Colitis

Keywords

Moderately to severely active Ulcerative Colitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MTX 12.5

Arm Type

Active Comparator

Arm Description

Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab

Arm Title

MTX 25 mg

Arm Type

Active Comparator

Arm Description

Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab

Intervention Type

Drug

Intervention Name(s)

MTX 12.5

Other Intervention Name(s)

MTX

Intervention Description

once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab

Intervention Type

Drug

Intervention Name(s)

MTX 25

Other Intervention Name(s)

MTX

Intervention Description

once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab

Intervention Type

Drug

Intervention Name(s)

Adalimumab

Other Intervention Name(s)

Humira

Intervention Description

Subjects will receive 18 weekly doses of adalimumab

Primary Outcome Measure Information:

Title

Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups

Description

Time Frame

Baseline up to Week 18

Secondary Outcome Measure Information:

Title

Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.

Description

Time Frame

Baseline up to Week 18

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]). Diagnosis of UC confirmed by established criteria, regardless of disease duration. Moderate to severely active UC, defined by a modified Mayo Score ≥6, with confirmed endoscopic activity by central reader (Mayo endoscopic subscore ≥2). Require initiation with adalimumab for induction of remission. Ability of subject to swallow study drug capsules. Ability of subject to participate fully in all aspects of this clinical trial. Written informed consent must be obtained and documented. Exclusion Criteria: Prior treatment with a TNF antagonist or biological therapy. Prior treatment with MTX. Disease limited to the rectum (proctitis). Documented presence of antibodies against adalimumab. Contraindication for anti-TNF or MTX therapy. Contraindication for endoscopy. Ostomy. Planned surgery.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Brian Feagan, MD

Organizational Affiliation

Robarts Research Institute - Western University

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

16339095

Citation

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.

Results Reference

background

PubMed Identifier

22326435

Citation

Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators; Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D'Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.e2. doi: 10.1053/j.gastro.2012.01.035. Epub 2012 Feb 8.

Results Reference

background

PubMed Identifier

21209123

Citation

Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5.

Results Reference

background

PubMed Identifier

12584368

Citation

Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. doi: 10.1056/NEJMoa020888.

Results Reference

background

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Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)

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