Analysis of the Peripheral Blood Mononuclear Cells of Patients With Ankylosing Spondylitis During Infliximab Treatment (Study P04465)(COMPLETED)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00778869
• Collaborator: (none)
• Enrollment: 10
• Arm: 1

Study Details

Study Description

Brief Summary

This is an open-label, controlled sub-study to the parent protocol (P04041, NCT00779935) to examine the expression profile of genes in patients in the active stage of ankylosing spondylitis (AS) compared to the healthy population as control, moreover to examine the changes in expression profile during anti-tumor necrosis factor (TNF)-alpha treatment (Remicade).

Condition or Disease	Intervention/Treatment	Phase
Spondylitis, Ankylosing	Biological: Remicade	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Whole Human Genome Oligo Microarray Analysis of the Peripheral Blood Mononuclear Cells of Patients With Ankylosing Spondylitis During Infliximab Treatment Compared to Healthy Controls
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Aug 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Remicade Remicade will be given at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54.	Biological: Remicade; Remicade will be given at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54.; Other Names: Infliximab SCH 215596

Outcome Measures

Primary Outcome Measures

1. Number of Genes Which Were Differentially Expressed [14 weeks]

   Differentially expressed genes were described as those which were at least 1.5 times up- or down-regulated and statistically different at a significance level of 0.05 using a paired t-test comparing 10 ankylosing spondylitis (AS) participants during tumor necrosis factor (TNF) alpha treatment (Remicade) with 10 matched controls. Control samples were previously obtained and not specifically collected for this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Diagnosis of ankylosing spondylitis proven by appropriate diagnostic methods (according to New York criteria).

• Refractory disease defined by failure of at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) during a 3-month period and failure of sulfasalazine in subjects with associated peripheral arthritis.

• Active disease defined by:

• sustained bath ankylosing spondylitis disease activity index (BASDAI) of at least 40 on a 0-100 scale and

• expert opinion based on clinical features.

• Age between 18 and 70 years.

• Subjects using NSAIDs and/or sulfasalazine must have been on a stable dose for at least 4 weeks prior to study initiation, and may continue medication during the treatment period, but the dose must not be increased above the baseline.

• Subjects must be capable to demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.

• Men and women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (eg, hormonal contraceptive, medically prescribed intrauterine device (IUD), condom in combination with spermicide) or be surgically sterilized (eg, hysterectomy or tubal ligation).

• Subjects must understand and be able to adhere to the dosing and visit schedules.

Exclusion Criteria:

• Subject with moderate or severe heart failure (New York Heart Association (NYHA) class III/IV).

• Remicade must not be given to subjects with a history of hypersensitivity to infliximab, to other murine proteins, or to any of the excipients.

• Subjects with pre-existing or recent onset of central nervous system demyelinating disorders.

• Age <18 or >70 years.

• Pregnant women, nursing mothers.

• Subjects who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.

• Subjects who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from infliximab therapy.

• Prior administration of infliximab or any other therapeutic agent targeted at reducing tumor necrosis factor (TNF) (eg, Etanercept, pentoxifylline, thalidomide or anti-CD4+ antibody).

• Current treatment with systemic corticosteroid.

• Treatment with any investigational drug within the previous 3 months.

• History of known allergies to murine proteins.

• Subjects having active or inactive tuberculosis (TB). All subjects must be evaluated for both active and inactive ('latent') TB. This evaluation should include a detailed medical history with personal history of TB or possible previous contact with TB and previous and/or current immunosuppressive therapy. Appropriate screening tests (ie, tuberculin skin test and chest x-ray) should be performed in all subjects.

• Serious infection, such as sepsis, abscesses, hepatitis, pneumonia, pyelonephritis in the previous 3 months. Less serious infections in the previous 3 months, such as acute respiratory tract infection (colds) or uncomplicated urinary tract infection need not be considered exclusions at the discretion of the treating physician.

• History of opportunistic infections such as herpes zoster within 2 months of study initiation. Evidence of active cytomegalovirus (CMV), active pneumocystis carinii, drug resistant atypical mycobacterium, etc.

• Documented human immunodeficiency virus (HIV) infection.

• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurological, or cerebral disease.

• Any currently known malignancy or pre-malignant lesions or any history of malignancy within the past 5 years (except non-melanoma skin cancer and surgically cured cervical cancer).

• Subjects with alcoholism, alcoholic liver disease, or other chronic liver disease.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00778869
• Other Study ID Numbers: P04465
• First Posted: Oct 24, 2008
• Last Update Posted: Jul 3, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Infliximab

Study Results

Participant Flow

Arm/Group Title	Remicade
Arm/Group Description	Remicade will be given as an intravenous infusion at a dose of 5 mg/kg at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Remicade
Arm/Group Description	Remicade will be given as an intravenous infusion at a dose of 5 mg/kg at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%

Outcome Measures

1. Primary Outcome

Title	Number of Genes Which Were Differentially Expressed
Description	Differentially expressed genes were described as those which were at least 1.5 times up- or down-regulated and statistically different at a significance level of 0.05 using a paired t-test comparing 10 ankylosing spondylitis (AS) participants during tumor necrosis factor (TNF) alpha treatment (Remicade) with 10 matched controls. Control samples were previously obtained and not specifically collected for this study.
Time Frame	14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remicade
Arm/Group Description	Remicade will be given as an intravenous infusion at a dose of 5 mg/kg at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54 in participants with AS.
Measure Participants	10
Number of Genes	54675
Number of Genes Up/Down Regulated	890
Number of Genes Highly Expressed	701

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remicade
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Student t-test
	Comments

Adverse Events

Adverse Event Reporting Description	Non-serious adverse events and serious adverse events were not required to be captured as part of the study database. They were captured in the parent protocol (P04041). Therefore, none were collected, and the number of participants at risk is zero.
Arm/Group Title	Remicade
Arm/Group Description	Remicade will be given as an intravenous infusion at a dose of 5 mg/kg at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54.
All Cause Mortality
	Remicade
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Remicade
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Remicade
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal investigator (PI) agrees not to publish or publicly present any interim results of study without prior written consent of sponsor. PI further agrees to provide 30 days written notice to sponsor prior to submission for publication or presentation to permit sponsor to review copies of abstracts or manuscripts for publication including without limitation slides and texts of oral or other public presentations and text of any transmission through any electronic media which report results.