Ulcerative ColitisPhase 2NCT01716039
Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)
A Phase 2 study testing MTX 12.5, MTX 25 and Adalimumab in people with Ulcerative Colitis, run by Alimentiv Inc..
Trial summary
Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- MTX 12.5, MTX 25 and Adalimumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- No sites listed yet
- Study dates
- Jun 2013to 18 Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis
Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.
Read the detailed description
Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.
- Conditions
- Ulcerative Colitis
- Being tested
- MTX 12.5, MTX 25, Adalimumab
- Keywords
- Moderately to severely active Ulcerative Colitis
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTX 12.5Drug
Also called MTX
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
MTX 25Drug
Also called MTX
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
AdalimumabDrug
Also called Humira
Subjects will receive 18 weekly doses of adalimumab
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
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
Measured: Baseline up to Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study startJun 2013
- Primary completion18 Jul 2016
- Study completion18 Jul 2016
Why it stopped: Unable to achieve recruitment target.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alimentiv Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott
- Responsible party
- Sponsor
- Investigators
- Brian Feagan, MD, Principal investigator, Robarts Research Institute - Western University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01716039
- Sponsor's protocol ID
- RP1204
- Status last verified
- Jun 2021
- First submitted
- 15 Oct 2012
- Last updated
- 23 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 16339095Rutgeerts 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.
PubMed 22326435Reinisch 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.
PubMed 21209123Baert 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.
PubMed 12584368
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT01716039
- Acronym / sponsor ID
- RP1204
- Conditions
- Ulcerative Colitis
- Keywords
- Moderately to severely active Ulcerative Colitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to achieve recruitment target.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Alimentiv Inc.University, hospital or other
- Collaborators
- Abbott
- Study start
- Jun 2013
- Primary completion
- 18 Jul 2016 (actual)
- Study completion
- 18 Jul 2016 (actual)
- First posted
- 29 Oct 2012 (estimated)
- Results
- Posted 23 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MTX 12.5 | Active comparator | Drug: MTX 12.5, Drug: AdalimumabReceive 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 |
| MTX 25 mg | Active comparator | Drug: MTX 25, Drug: AdalimumabOnce 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 |
| Placebo | Placebo comparator | Drug: AdalimumabOnce 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTX 12.5Also: MTXonce 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 | Drug | MTX 12.5 |
| MTX 25Also: MTXonce 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 | Drug | MTX 25 mg |
| AdalimumabAlso: HumiraSubjects will receive 18 weekly doses of adalimumab | Drug | MTX 12.5, MTX 25 mg, Placebo |
Primary outcome
Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups
Time frame: Baseline up to Week 18
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
1 secondary outcome
Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.
Time frame: Baseline up to Week 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16339095Rutgeerts 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.
- Background: PubMed 22326435Rutgeerts 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.
- Background: PubMed 21209123Reinisch 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.
- Background: PubMed 12584368Baert 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Feagan, MD principal investigator
Robarts Research Institute - Western University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MTX 12.5, MTX 25 and Adalimumab in people with Ulcerative Colitis, run by Alimentiv Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups (time frame: Baseline up to Week 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01716039, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2021.