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Crohn's DiseasePhase 4OPTIMISTNCT00752622

Treatment With Infliximab in a Medical Setting (Study P05587)

A Phase 4 study testing Infliximab 5 mg/kg, Infliximab 5 mg/kg every 6 weeks and Infliximab 7 mg/kg every 8 weeks in people with Crohn's Disease, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open-label, interventional study where a subset of participants will be randomized to one of two treatment-optimization strategies. Participants with moderate to severe Crohn's disease (CD) will receive induction treatment comprised of 3 infusions of infliximab at Weeks 0, 2, and 6. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Crohn's Disease
What is being tested?
Infliximab 5 mg/kg, Infliximab 5 mg/kg every 6 weeks and Infliximab 7 mg/kg every 8 weeks
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
No sites listed yet
Study dates
Nov 2008to Jun 2010
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women >=18 years of age
  • Moderate to severe CD (Crohn's Disease Activity Index [CDAI] >= 220 and <= 450)
  • CD of at least 3 months duration confirmed within the past 2 years by radiography and/or endoscopy
  • Biologic-naïve
  • If using 5-Aminosalicylic Acid (5-ASA), there must be at least 4 weeks of stable dosage prior to screening
  • If using azathioprine or 6-mercaptopurine, the start date must be at least 3 months prior to screening and the dose must be stable for at least 6 weeks prior to screening
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  • If using methotrexate, the participant must have been using methotrexate with a stable dosage of at least 6 weeks prior to screening
  • Participants must be off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroids at baseline must not exceed 30 mg of prednisone equivalent
  • Participants are considered eligible according to the following tuberculosis (TB) screening criteria:
  • Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination
  • Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication
  • Within 3 months prior to the first administration of study medication, either have negative OR have a newly identified positive diagnostic TB test result (defined as at least 1 positive tuberculin skin test) during screening in which active TB has been ruled out, and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study medication
  • Participants must have had a chest X-ray within 3 months prior to screening with no evidence of current or old active TB
  • Participants' screening and baseline clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) must be within the following parameters:
  • Hemoglobin >=10 g/dL (100 g/L)
  • White blood cells (WBCs) >=3.5 x 109/L
  • Neutrophils >=1.5 x 10^9/L
  • Platelets >=100 x 10^9/L
  • Serum creatinine <1.5 mg/dL (or <133 μmol/L)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gammaglutamyltransferase <=1.5 x upper limit of normal (ULN);
  • Total bilirubin <=1 x ULN
  • Antibiotics for the treatment of CD (e.g., ciprofloxacin and metronidazole) must have been discontinued at least 3 weeks prior to screening
  • Participants must be free of any clinically significant condition or situation, other than CD that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study
  • Participants are willing and able to adhere to the study visit schedule and other protocol requirements
  • Participants are capable of providing written informed consent, which must be obtained prior to conducting any protocol-specified procedures
  • Sexually-active women of child-bearing potential must agree to use a medically accepted method of contraception prior to screening, while receiving protocol specified medication, and for 6 months after stopping the medication
  • Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study
  • Female participants of childbearing potential must have a negative serum pregnancy test (beta-hCG) at screening
  • have an increased Harvey-Bradshaw Index (HBI) score >=3 points over the week 10 evaluation score and a CDAI score >=175
  • have received regular infusions of Infliximab (IFX) every 8 weeks during the observational phase with a maximum interval of no more than 10 weeks between each infusions
  • having previous doses of IFX of >= 4.7 mg/kg

Who cannot join

  • Are pregnant or plan to become pregnant during the study period; participants who are breast feeding
  • Have been treated with excluded drugs prior to entry: any biological or anti- Tumor necrosis factor (anti-TNF) agent such as infliximab, adalimumab, certolizumab, etanercept, pentoxifylline, or thalidomide
  • Have had a serious infectious disease in the 8 weeks prior to entry
  • Have active perianal fistulas and a Perianal disease activity index (PDAI) score >10
  • Have presumed fibro-stenotic stricture or acute bowel obstruction
  • Have had live vaccination in the 6 weeks prior to entry
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  • Have known intolerance to study drug
  • Have a history of myocardial infarction, congestive heart failure, coronary artery disease, or arrhythmias in the last 6 months
  • Have a history of malignancy (within the past 5 years) with the exception of carcinoma in situ of the cervix or localized basal cell skin cancer that have been adequately treated
  • Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease
  • Have a history of demyelinating disease such as multiple sclerosis
  • Have a positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV) antibody
  • Have renal, hepatic, hematological, cardiovascular, pulmonary, neurological, psychiatric, immunologic, gastrointestinal, endocrine, or other diseases if they are clinically significant. (A clinically significant disease is defined as one which in the opinion of the investigator can put the participants at risk because of participation in the study or a disease which can influence the participant's ability to participate in the study or affect the results of the
  • study)
  • Have clinically significant abnormal laboratory test results, unless regarded by the investigator as related to CD
  • Have a history of alcohol or drug abuse
  • Are unable to comply with the protocol
  • Have any clinically significant findings in the physical examination that, in the investigator's judgment, may interfere with the study evaluation or affect participant safety
  • Are in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study
  • Are participating in any other clinical study(ies) except for registries
  • Are on the staff, affiliated with, or a family member of the staff personnel directly involved with this study
  • Are allergic to or have sensitivity to the study drug or any of its excipients

About this study

Official title: Optimization of Treatment With Infliximab in a Medical Setting

This is an open-label, interventional study where a subset of participants will be randomized to one of two treatment-optimization strategies. Participants with moderate to severe Crohn's disease (CD) will receive induction treatment comprised of 3 infusions of infliximab at Weeks 0, 2, and 6. The participants will be evaluated at Week 10. Participants who are in clinical response will enter the observational phase of the study where they will receive standard of care treatment, as per the infliximab product monograph. Participants who lose response, may qualify for entry into the interventional phase of the study, where they will be randomized to one of the following treatment-optimization arms: 1) dose increase: infliximab 7 mg/kg, every 8 weeks or 2) shortened interval: infliximab 5 mg/kg every 6 weeks.

Note: Due to early study termination, no statistical analysis was performed for the interventional part of this study, therefore, endpoints dedicated to this phase of the study have not been analyzed.

Conditions
Crohn's Disease
Being tested
Infliximab 5 mg/kg, Infliximab 5 mg/kg every 6 weeks, Infliximab 7 mg/kg every 8 weeks
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Infliximab 5 mg/kgBiological

    Also called Remicade, SCH 215596

    Participants received Infliximab 5 mg/kg intravenously (IV) at weeks 0, 2 and 6 during the induction phase. At Week 10, those who were in clinical response received further treatment every 8 weeks during the observational phase

  • Infliximab 5 mg/kg every 6 weeksBiological

    Participants with loss of response in the observational phase were randomized at entry into the interventional phase received 5 mg/kg IV every 6 weeks (shortened interval group)

  • Infliximab 7 mg/kg every 8 weeksBiological

    Participants with loss of response in the observational phase were randomized at entry into the interventional phase received 7 mg/kg IV every 8 weeks (increased dose group)

Study groups in NCT00752622
Study groupRoleWhat they receive
Shortened intervalExperimentalInfliximab 5 mg/kg, then Infliximab 5 mg/kg every 6 weeks
Receives: Biological: Infliximab 5 mg/kg; Biological: Infliximab 5 mg/kg every 6 weeks
Increased doseExperimentalInfliximab 5 mg/kg, then Infliximab 7 mg/kg every 8 weeks
Receives: Biological: Infliximab 5 mg/kg; Biological: Infliximab 7 mg/kg every 8 weeks

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Had a Clinical Response Using the Crohn's Disease Activity Index (CDAI) at Week 24 in the Interventional Phase

    The CDAI incorporates 8 items that are indicators of disease severity. Scores range from 0 to ~600; higher scores indicate worse disease activity. Participants with scores below 150 have inactive disease whereas those with scores above 450 are considered critically ill. Participants provided completed CDAI diary cards and were considered as responders in the interventional phase if their CDAI score at week 24 was decreased by 70 points or greater over their CDAI score at randomization into the interventional phase, or if their week 24 CDAI score is <= 150. Baseline is value at randomization.

    Measured: Baseline and Week 24 of the Interventional phase

  2. Mean Change From Baseline in Harvey-Bradshaw Index (HBI)

    Mean change in HBI score from Baseline to Week 10, 30, and 54. HBI score consists of clinical parameters: general well-being (0-4), abdominal pain (0-3), number of liquid stools per day, abdominal mass (0-3), and complications (score 1 per item). Total score is the sum of individual parameters. Minimum score is 0 and no pre-specified maximum score as it depends on the number of liquid stools. Lower scores indicate better well being. Clinical response/ long-term response is defined as a decrease by 3 or more points from baseline value. Loss of response is defined as an increase of >= 3 points.

    Measured: Baseline and Evaluation Week 10, Week 30 and Week 54 of the Observational Phase

Secondary outcomes (5)

  1. Number of Participants That Required Treatment Optimization in the Observational Phase

    Participants required treatment-optimization if:

    • Disease progression/lack of response after entering observational phase; or
    • Participant was successfully randomized into the interventional phase

    The definition of loss of response was as follows:

    • An increased HBI score >= 3 points over the week 10 evaluation score and a CDAI score >= 175.

    Despite:

    • having received regular infusions of infliximab every 8 weeks during the observational phase with a maximum interval of no > 10 weeks between each infusion, and
    • having received previous doses of infliximab of >= 4.7 mg/kg.

    Measured: Week 54 in the Observational Phase

  2. Number of Participants Who Had a Clinical Response Using the CDAI at Weeks 14-16 and 48 in the Interventional Phase

    The CDAI incorporates 8 items that are indicators of disease severity. Scores range from 0 to ~600; higher scores indicate worse disease activity. Participants with scores below 150 have inactive disease whereas those with scores above 450 are considered critically ill.

    Clinical response was defined as a 70-point reduction in CDAI score from randomization into the interventional phase or CDAI < 150 at week 14-16 and 48 in the Interventional Phase. Baseline is value at randomization.

    Measured: Baseline and Weeks 14-16 and 48 in the Interventional Phase

  3. Number of Participants Who Had a Clinical Response Using the CDAI-100 at Weeks 14-16, 24 and 48 in the Interventional Phase

    The CDAI incorporates 8 items that are indicators of disease severity. Scores range from 0 to ~600; higher scores indicate worse disease activity. Participants with scores below 150 have inactive disease whereas those with scores above 450 are considered critically ill.

    Clinical response was defined as a 100-point reduction in CDAI score from randomization into the interventional phase or CDAI < 150 at weeks 14-16, 24 and 48 in the Interventional Phase. Baseline is value at randomization.

    Measured: Baseline and Weeks 14-16, 24 and 48 in the Interventional Phase

  4. Number of Participants Who Had Clinical Remission in the Interventional Phase

    The CDAI incorporates 8 items that are indicators of disease severity. Scores range from 0 to ~600; higher scores indicate worse disease activity. Participants with scores below 150 have inactive disease whereas those with scores above 450 are considered critically ill.

    Clinical remission was defined as CDAI < 150 at weeks 14-16, 24 and 48 in the Interventional Phase.

    Measured: Weeks 14-16, 24 and 48 in the Interventional Phase

  5. Number of Participants Who Had Clinical Remission Off Steroids in the Interventional Phase

    Number of participants who were in clinical remission and off systemic corticosteroids at visit.

    The CDAI incorporates 8 items that are indicators of disease severity. Scores range from 0 to ~600; higher scores indicate worse disease activity. Participants with scores below 150 have inactive disease whereas those with scores above 450 are considered critically ill. Clinical remission was defined as CDAI < 150 at weeks 14-16, 24 and 48 in the Interventional Phase.

    Measured: Weeks 14-16, 24 and 48 in the Interventional Phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionJun 2010
  4. Study completionJun 2010

Why it stopped: Factors that led to termination: recruitment challenges and a lower incidence of flares than estimated, causing a high risk of the study being underpowered.

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00752622
Sponsor's protocol ID
P05587
Acronym
OPTIMIST
Status last verified
Mar 2017
First submitted
12 Sep 2008
Last updated
13 Apr 2017
Data monitoring committee
No
Individual data sharing
Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Infliximab 5 mg/kg, Infliximab 5 mg/kg every 6 weeks and Infliximab 7 mg/kg every 8 weeks in people with Crohn's Disease, run by Merck Sharp & Dohme LLC.

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 31 inclusion and 22 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 13 Apr 2017. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 22 Jul 2011). 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?

Number of Participants Who Had a Clinical Response Using the Crohn's Disease Activity Index (CDAI) at Week 24 in the Interventional Phase (time frame: Baseline and Week 24 of the Interventional phase). The study lists 2 primary outcomes in all. 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 NCT00752622.

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 13 Apr 2017.

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