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

NCT01716039 | Terminated Phase 2 Results

• 1 other identifier: RP1204
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ulcerative Colitis

Keywords

Moderately to severely active Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline up to Week 18

Secondary Outcomes (1)

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

  Baseline up to Week 18

Study Arms (3)

MTX 12.5

ACTIVE COMPARATOR

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

Drug: MTX 12.5; Drug: Adalimumab

MTX 25 mg

ACTIVE COMPARATOR

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

Drug: MTX 25; Drug: Adalimumab

Placebo

PLACEBO COMPARATOR

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

Drug: Adalimumab

Interventions

MTX 12.5 DRUG

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

Also known as: MTX

MTX 12.5

MTX 25 DRUG

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

Also known as: MTX

MTX 25 mg

Adalimumab DRUG

Subjects will receive 18 weekly doses of adalimumab

Also known as: Humira

MTX 12.5; MTX 25 mg; Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alimentiv Inc.: lead
• Abbott: collaborator

Related Publications (4)

• 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.

  PMID: 16339095 BACKGROUND

• 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.

  PMID: 22326435 BACKGROUND

• 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.

  PMID: 21209123 BACKGROUND

• 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.

  PMID: 12584368 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr.Jenny Jeyarajah (Sr. Biostatistician)
• Organization: Alimentiv (Formerly Robarts Clinical Trails)

jenny.jeyarajah@alimentiv.com

Study Officials

• Brian Feagan, MD

  Robarts Research Institute - Western University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2012
• First Posted: October 29, 2012
• Study Start: June 1, 2013
• Primary Completion: July 18, 2016
• Study Completion: July 18, 2016
• Last Updated: June 23, 2021
• Results First Posted: June 23, 2021

Record last verified: 2021-06