TerminatedNCT00752622OPTIMISTUpdated Apr 13, 2017Results posted

Treatment With Infliximab in a Medical Setting (Study P05587)

A Phase 4 interventional study of Infliximab 5 mg/kg and Infliximab 5 mg/kg every 6 weeks in Crohn's Disease, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-04-13.

Sponsored by Merck Sharp & Dohme LLC · Phase 4, Interventional, and Treatment

Why this study was terminated

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

Phase: Phase 4
Study type: Interventional
Enrollment: 100
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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. 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 studied

Crohn's Disease

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Crohn Disease 1,880

In context

Crohn Disease

1,880 studies on the registry are indexed under Crohn Disease; 462 are open to participants now.

This study's enrollment of 100 is above the median of 66 across 1,188 interventional studies indexed under Crohn Disease.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
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

Exclusion criteria

Exclusion Criteria:

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
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

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 100 participants (actual)

Study arms

Experimental
Shortened interval
Infliximab 5 mg/kg, then Infliximab 5 mg/kg every 6 weeks
Biological: Infliximab 5 mg/kg · Biological: Infliximab 5 mg/kg every 6 weeks
Experimental
Increased dose
Infliximab 5 mg/kg, then Infliximab 7 mg/kg every 8 weeks
Biological: Infliximab 5 mg/kg · Biological: Infliximab 7 mg/kg every 8 weeks

Interventions

BiologicalInfliximab 5 mg/kg
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
Also known as: Remicade, SCH 215596
BiologicalInfliximab 5 mg/kg every 6 weeks
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)
BiologicalInfliximab 7 mg/kg every 8 weeks
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)

What researchers measure

Primary outcomes

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.
Time frame: Baseline and Week 24 of the Interventional phase
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.
Time frame: Baseline and Evaluation Week 10, Week 30 and Week 54 of the Observational Phase

Secondary outcomes

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.
Time frame: Week 54 in the Observational Phase
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.
Time frame: Baseline and Weeks 14-16 and 48 in the Interventional Phase
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.
Time frame: Baseline and Weeks 14-16, 24 and 48 in the Interventional Phase
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.
Time frame: Weeks 14-16, 24 and 48 in the Interventional Phase
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.
Time frame: Weeks 14-16, 24 and 48 in the Interventional Phase

Results

Posted Jul 22, 2011

Limitations and caveats

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.

Participant flow

Induction Phase

Participant flow — Induction Phase
Milestone	Infliximab
Started	100
Completed	65
Not completed	35
Withdrew: Adverse event	3
Withdrew: Other	3
Withdrew: Non-responder	14
Withdrew: Withdrawal by subject	1
Withdrew: Premature study termination	14

Observational Phase

Participant flow — Observational Phase
Milestone	Infliximab
Started	65
Completed	22
Not completed	43
Withdrew: Premature study termination	36
Withdrew: Non-responder	2
Withdrew: Withdrawal by subject	2
Withdrew: Adverse event	1
Withdrew: Other	2

Interventional Phase

Participant flow — Interventional Phase
Milestone	Infliximab
Started	8
Completed	0
Not completed	8
Withdrew: Non-responder	2
Withdrew: Physician decision	1
Withdrew: Premature study termination	5

Outcome measures

PrimaryNumber 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.

Time frame:: Baseline and Week 24 of the Interventional phase

No measurements were reported for this outcome.

PrimaryMean 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.

Time frame:: Baseline and Evaluation Week 10, Week 30 and Week 54 of the Observational Phase
Reported as:: Mean · score on a scale

Mean Change From Baseline in Harvey-Bradshaw Index (HBI)
score on a scale	Infliximab
Baseline (n= 98)	9.5 ± 3.23
Change at Week 10 (n= 81)	-5.88 ± 3.890
Change at Week 30 (n= 37)	-7.19 ± 2.998
Change at Week 54 (n= 15)	-7.93 ± 3.173

Statistical analysis

Infliximab · t-test, 2 sided · p = <.0001
Infliximab · t-test, 2 sided · p = <.0001
Infliximab · t-test, 2 sided · p = <.0001

SecondaryNumber 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.

Time frame:: Week 54 in the Observational Phase
Reported as:: Number · Participants

Number of Participants That Required Treatment Optimization in the Observational Phase
Participants	Infliximab
Number of Participants That Required Treatment Optimization in the Observational Phase	10

SecondaryNumber 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.

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

No measurements were reported for this outcome.

SecondaryNumber 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.

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

No measurements were reported for this outcome.

SecondaryNumber of Participants Who Had Clinical Remission in the Interventional Phase

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

No measurements were reported for this outcome.

SecondaryNumber 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.

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

No measurements were reported for this outcome.

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Infliximab 5 mg/kg Then Not Randomized	—	7/92 (7.6%)	42/92 (45.7%)
Infliximab 5 mg/kg Then Randomized	—	3/8 (37.5%)	7/8 (87.5%)

Most frequent serious events

Showing 10 of 12

Most frequent serious events
Event	Infliximab 5 mg/kg Then Not Randomized	Infliximab 5 mg/kg Then Randomized
Anal FistulaGastrointestinal disorders	0/92	1/8
Crohn's DiseaseGastrointestinal disorders	2/92	1/8
Intestinal ObstructionGastrointestinal disorders	1/92	1/8
Small Intestinal ObstructionGastrointestinal disorders	1/92	1/8
Anal AbscessInfections and infestations	0/92	1/8
BacteraemiaInfections and infestations	0/92	1/8
Intestinal PerforationGastrointestinal disorders	1/92	0/8
Infusion Related ReactionGeneral disorders	1/92	0/8
Biliary ColicHepatobiliary disorders	1/92	0/8
Cholecystitis AcuteHepatobiliary disorders	1/92	0/8

Most frequent other events

Showing 10 of 26

Most frequent other events
Event	Infliximab 5 mg/kg Then Not Randomized	Infliximab 5 mg/kg Then Randomized
Crohn's DiseaseGastrointestinal disorders	5/92	2/8
Tooth AbscessInfections and infestations	0/92	2/8
Abdominal PainGastrointestinal disorders	7/92	1/8
Abdominal TendernessGastrointestinal disorders	4/92	1/8
Anal FissureGastrointestinal disorders	0/92	1/8
ConstipationGastrointestinal disorders	2/92	1/8
DiscomfortGeneral disorders	0/92	1/8
PyrexiaGeneral disorders	2/92	1/8
Clostridium Difficile ColitisInfections and infestations	0/92	1/8
Ear InfectionInfections and infestations	0/92	1/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Infliximab
Mean	38.4 ± 13.16

Sex/Gender, Customized
Sex/Gender, Customized(participants)	Infliximab
Female	54
Male	44
Excluded from analysis	2

Study locations

No study locations are listed for this record.

References and documents

Individual participant data

Plan to share: 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

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 13, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00752622
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Sep 15, 2008
Start date: Nov 2008
Primary completion: Jun 2010
Completion: Jun 2010
Results posted: Jul 22, 2011
Last update: Apr 13, 2017

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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Treatment With Infliximab in a Medical Setting (Study P05587)

Study summary

Conditions studied

Browse trials for

In context

Crohn Disease

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Individual participant data

Updates

Registry details

Key details

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria