Safety and Efficacy of Abatacept Versus Placebo in Participants With Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

Official title:

A Phase IIB, Multi-Dose, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo in the Treatment of Psoriatic Arthritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00534313
• Other study ID #: IM101-158
• Secondary ID: EUDRACT 2007-004
• Status: Terminated
• Phase: Phase 2
• First received: September 20, 2007
• Last updated: July 25, 2012
• Start date: November 2007
• Est. completion date: May 2011

Study information

• Verified date: July 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine an optimal abatacept dosing regimen for the treatment of active arthritis due to psoriatic arthritis in patients who have had a prior inadequate response to disease-modifying antirheumatic drugs, including methotrexate and tumor necrosis factor alpha-blockade compounds.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 191
• Est. completion date: May 2011
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Meeting classification criteria for psoriatic arthritis for a duration of disease of at least 3 months

• Prior failure (inefficacy or intolerance) of therapy with disease-modifying antirheumatic drugs; if patient had prior failure of methotrexate, he or she must have been taking at least 15 mg per week for at least 2 months

• If recent failure(inefficacy or intolerance) of a tumor necrosis factor a-blockade compound, participant must be washed out prior to first dose: 56 days for infliximab and 28 days for etanercept and adalimumab

• Disease activity as defined by a tender joint count of =3, swollen joint count of =3, and clinically detectable synovitis at screening and Day 01 (prior to infusion)

• Active psoriasis with a qualifying target lesion =2 cm in diameter

• Able to undergo magnetic resonance imaging

• Use of appropriate birth control by women of child bearing potential (WOCBP)

Key Exclusion Criteria:

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last dose of investigational product

• Women who are pregnant or breastfeeding or who plan to become pregnant or to start breastfeeding during the duration of the study

• Women with a positive pregnancy test on enrollment or prior to investigational product administration.

• Participants scheduled for or anticipating joint replacement surgery.

• Those with a recent history of clinically significant drug or alcohol abuse

• Concomitant illness that in the investigator's opinion is likely to require systemic glucocorticosteroid therapy during the study (for example: moderate to severe asthma)

• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, pulmonary, cardiac, neurologic, ophthalmologic, or cerebral disease.

• Unwillingness or inability to undergo screening based on current local or country guidelines/standards to evaluate the presence of cancer

• Cancer within the last 5 years

• Current malignancy or signs of possible malignancy detected by screening procedures for which the workup to exclude malignancy has not been completed or malignancy cannot be excluded

• At risk for or history (within 3 years) of tuberculosis

• Any serious bacterial infection within the last 3 months, not treated and resolved with antibiotics, or any chronic bacterial infection (such as, but not limited to, chronic pyelonephritis, osteomyelitis, and bronchiectasis)

• Evidence of active or latent bacterial or viral infection infections at the time of potential enrollment

• Herpes zoster or cytomegalovirus resolving less than 2 months prior to signing informed consent

• Receipt of any live vaccines within 3 months of the anticipated first dose of study medication or anticipation of the need for a live vaccine at any time during and for 3 months after the duration of the study

Long-term period participants: Must have met eligibility criteria for short-term period and completed short-term (24-week) period of the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Abatacept
Solution, intravenous, monthly, short-term = 24 weeks (6 months)
• Placebo
Solution, intravenous, placebo (double dummy), monthly, short-term = 24 weeks (6 months)

Locations

Country	Name	City	State
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Santa Fe
Australia	Local Institution	Cairns	Queensland
Australia	Local Institution	Fitzroy, Melbourne	Victoria
Australia	Local Institution	Maroochydore	Queensland
Belgium	Local Institution	Hasselt
Belgium	Local Institution	Leuven
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Quebec
Canada	Local Institution	St. John'S	Newfoundland and Labrador
Canada	Local Institution	Trois-Rivieres	Quebec
France	Local Institution	Chambray Les Tours
France	Local Institution	Lille
France	Local Institution	Montpellier Cedex 5
Germany	Local Institution	Frankfurt/Main
Germany	Local Institution	Hamburg
Germany	Local Institution	Hildesheim
Italy	Local Institution	Napoli
Italy	Local Institution	Potenza
Italy	Local Institution	Reggio Emilia
Netherlands	Local Institution	Amsterdam
Norway	Local Institution	Lillehammer
South Africa	Local Institution	Panorama	Western Cape
Spain	Local Institution	A Coruna
United States	Chase, Walter F.	Austin	Texas
United States	Joao Nascimento	Bridgeport	Connecticut
United States	Arthritis Clinic & Carolina Bone & Joint, Pa	Charlotte	North Carolina
United States	Deaconess Hospital	Cincinnati	Ohio
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	St. Paul Rheumatology P.A.	Eagan	Minnesota
United States	Rheumatology Associates Of North Alabama	Huntsville	Alabama
United States	Midwest Arthritis Center	Kalamazoo	Minnesota
United States	Justus Fiechtner, Md, Mph	Lansing	Michigan
United States	Health Research Of Oklahoma	Oklahoma City	Oklahoma
United States	Desert Medical Advances	Palm Desert	California
United States	Stanford University School Of Medicine	Palo Alto	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	Arthritis Northwest	Spokane	Washington
United States	New England Research Associates, Llc	Trumbull	Connecticut
United States	Boling Clinical Trials	Upland	California
United States	Rheumatic Disease Associates, Ltd.	Willow Grove	Pennsylvania
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Norway,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long-term Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, and AEs of Interest	Presp=prespecified; acute= =1 hour after start of infusion; periinfusional= =24 hours after start of infusion. AE=any new unfavorable symptom or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=an unfavorable medical event that at any dose results in death, significant disability, drug dependency/abuse, hospitalization or prolonged hospitalization; is life-threatening, an important medical event, or a congenital anomaly/birth defect. Drug-related=possibly, probably, or certainly related and of unknown relationship to study drug.	From Day 169 to Day 729	Yes
Primary	Short-term Period: Number of Participants With ACR 20 Response at Day 169	An ACR 20 responder was a participant who had a reduction of 20% or more from baseline in scores for both tender and swollen joints and had a reduction from baseline of 20% or more in 3 out of the following 5 assessments: participant's assessment of disease activity, participant's global assessment of disease activity, investigator's global assessment of disease activity, participant's assessment of physical function by HAQ-DI, and Disease Activity Score 28-C reactive protein.	At Day 169 from Baseline	No
Secondary	Long-term Period: Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR 50, ACR 70, ACR 90 Responses at Days 365 and 729	An ACR 20 (50, 70, 90) responder was a participant whose counts for both tender and swollen joints was reduced by 20% (50%, 70%, 90%, respectively) or more from baseline and who had a reduction of 20% (50%, 70%, 90%, respectively) or more from baseline in 3 of the following assessments: participant's assessment of disease activity, participant's global assessment of disease activity, Investigators Global Response, participant's assessment of physical function by Health Assessment Questionnaire Disability Index, and Disease Activity Score 28 based on C-reactive protein.	At Days 365 and 729 from Baseline	No
Secondary	Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729	IGA score indicates lesion induration, scaling, and erythema: 0=clear (no signs of plaque psoriasis except for residual discoloration); 1=almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2=mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3=moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates).	From Day 169 to Days 365 and 729	No
Secondary	Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729	Target lesion score is a measurement of the degree of erythema, induration, and scale of a psoriatic lesion, at least 2 cm in diameter, selected as a target for response throughout the study period. The scores assigned were 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value.	From Baseline to Days 365 and 729	No
Secondary	Long-term Period: Mean Change From Baseline in the Short-form 36 (SF-36), Version 2, Domain and Component Scores at Days 365 and 729	PCS=physical component score; MCS=mental component score. The SF-36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.	At Days 365 and 729 from baseline	No
Secondary	Long-term Period: Number of Participants Achieving A Reduction of At Least 0.3 Unit From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Days 365 and 729	Per the HAQ-DI, participants assessed their own ability to perform the following tasks: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity over a period by marking their responses on a questionnaire. Scoring of the HAQ-DI: 0=without any difficulty; 1=with some difficulty; 2=with much difficulty); and 3=unable to do. Greater score=greater disability. Responders with a >= 0.3 unit decrease in index scores from baseline to days 365 and 729 were considered to be improved.	Days 365 and 729 from baseline	No
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Hematology	LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormalities are laboratory measurements marked as abnormal, per predefined study criteria, at any study time point. Criteria: Hemoglobin >3 g/dL decrease from pre-Rx value; hematocrit <0.75*pre-Rx value; erythrocytes <0.75*pre-Rx value; platelets <0.67*LLN (or, if pre-Rx value	From Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)	LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Laboratory measurements are marked as abnormal per predefined study criteria, at any study time point. Criteria for the data presented. Leukocytes <0.75*LLN or >1.25*ULN (or, if pre-Rx value	From Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry	ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) >2*ULN (if pre-Rx >ULN, >3*pre-Rx); aspartate aminotransferase (AST), alanine transaminase (ALT) >3*ULN (if pre-Rx >ULN, >4*pre-Rx); bilirubin (total) >2*ULN (if pre-Rx >ULN, >4*pre-Rx); blood urea nitrogen (BUN) >2*pre-Rx; creatinine >1.5*pre-Rx.	Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)	LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Sodium <0.95*LLN or >1.05*ULN (if pre-Rx	Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)	LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Glucose <65 or >220 mg/dL; glucose (fasting)<0.8*LLN or >1.5*ULN (if pre-Rx	From Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis	Pre-Rx=pretreatment. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase, red blood cells (RBC), white blood cells (WBC) >=2+ (or, if value >=4, or if pre-Rx value=0 or 0.5, >= 2* or if pre-RX value =1, >=3, or if pre-Rx =2 or 3, >=4).	From Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants Who Died and With SAEs, AEs, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Drug-related AEs, and Drug-related SAEs	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.	From Baseline to Day 169	Yes
Secondary	Short-term Period: Number of Participants With an IGA Score of Clear or Almost Clear at Day 169	Score indicates lesion induration, scaling, and erythema: 0 = clear (no signs of plaque psoriasis except for residual discoloration); 1 = almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2 = mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3 = moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates).	At Day 169 from Baseline	No
Secondary	Short-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Day 169	Target lesion score measures the degree of erythema, induration, and scale of a psoriatic lesion with a diameter of at least 2 cm, selected as a target for response throughout the study period. Scores: 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value.	At Day 169 from Baseline	No
Secondary	Short-term Period: Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies (Anti-Abatacept-C)	Meso Scale Discovery electrochemiluminescence, a validated, sensitive immunoassay technique (anti-abatacept assay C) was used to measure serum levels of abatacept-specific antibodies against the whole molecule (both the CTLA4 and possibly immunoglobulin G portion [anti-abatacept antibody].	From Baseline to Day 169	Yes
Secondary	Short-term Period: Mean Change From Baseline in the Mental Component Summary Score as Measured by the Short-form 36 at Day 169	PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.	At Day 169 from Baseline	No
Secondary	Short-term Period: Mean Serum Concentrations of Abatacept	Abatacept was assayed using a validated enzyme linked immunosorbent assay method (ELISA). Serum concentration versus time data was analyzed in the descriptive pharmacokinetic (PK) analysis.	Days 1, 15, 29, 57, 85, 113, 141, and 169	No
Secondary	Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept	Abatacept was assayed using a validated ELISA method. Cmin of abatacept was obtained from concentration versus time data.	Days 1, 15, 29, 57, 85, 113, 141, and 169	No
Secondary	Short-term Period: Population Pharmacokinetic (POPPK) Analysis of the Pharmacokinetic (PK) Parameters	PK data: summaries of concentrations and concentration versus time plots were obtained. These data were to be used to develop a POPPK model using a nonlinear mixed-effects model. Prediction of PK data for each of the 3 abatacept treatment groups using POPPK methodology was not performed, because it would not provide any relevant information over the observed PK data.	Days 1, 15, 29, 57, 85, 113, 141, and 169	No
Secondary	Short-term Period: Mean Change From Baseline in Physical Component Summary Score as Measured by the Short-form 36 at Day 169	PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.	At Day 169 from Baseline	No
Secondary	Short-term Period: Number of Participants Achieving a Reduction of At Least 0.3 Unit From Baseline in HAQ-DI Scores at Day 169	The HAQ-DI assesses a participant's ability to perform the following tasks: dress/groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity over a period by marking their response on a questionnaire. Responses/scores range from: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=to unable to do. Higher total score=greater disability.	At Day 169 from Baseline	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm