Register a trial

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:00pm (AEST) on Thursday 10th of April for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.


The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.


With activity expected to increase on the ANZCTR again, there may be extended wait times while we process pending studies, with priority being given to those trials submitted in February. Thank you for your patience.


Reset your password and enable multi-factor authentication (MFA)


For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.


  1. Go to the Login page, click ‘reset password’ and follow the instructions.
  2. Check your email for the link to set a new password.
  3. Create a new password that meets requirements.
  4. Return to the Login page and enter your new password. A verification code will be sent to your email.
  5. Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01526057




Registration number
NCT01526057
Ethics application status
Date submitted
1/02/2012
Date registered
3/02/2012

Titles & IDs
Public title
A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01)
Scientific title
A RANDOMIZED, DOUBLE-BLIND, STUDY COMPARING THE PHARMACOKINETICS AND PHARMACODYNAMICS, AND ASSESSING THE SAFETY OF PF-05280586 AND RITUXIMAB IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS ON A BACKGROUND OF METHOTREXATE WHO HAVE HAD AN INADEQUATE RESPONSE TO ONE OR MORE TNF ANTAGONIST THERAPIES
Secondary ID [1] 0 0
ICON 9002/010
Secondary ID [2] 0 0
B3281001
Universal Trial Number (UTN)
Trial acronym
REFLECTIONS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - PF-05280586
Treatment: Other - MabThera
Treatment: Other - Rituxan

Experimental: A - PF-05280586 -

Active comparator: B - Rituximab EU -

Active comparator: C- Rituximab-US -


Treatment: Other: PF-05280586
1000 mg, IV on days 1 and 15

Treatment: Other: MabThera
1000 mg, IV on days 1 and 15

Treatment: Other: Rituxan
1000 mg, IV on days 1 and 15
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Serum Concentration (Cmax) of Rituximab
Assessment method [1] 0 0
Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.
Timepoint [1] 0 0
Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Primary outcome [2] 0 0
AUC 0-inf of Rituximab
Assessment method [2] 0 0
The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity.
Timepoint [2] 0 0
Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Secondary outcome [1] 0 0
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
Assessment method [1] 0 0
The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration.
Timepoint [1] 0 0
Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Secondary outcome [2] 0 0
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)
Assessment method [2] 0 0
The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T.
Timepoint [2] 0 0
Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Secondary outcome [3] 0 0
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
Assessment method [3] 0 0
The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T.
Timepoint [3] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [4] 0 0
Minimum Post-Baseline CD19+ B-cell Count (/uL)
Assessment method [4] 0 0
The lowest CD19+ B-cell count measured in a participant's blood post-baseline.
Timepoint [4] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [5] 0 0
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
Assessment method [5] 0 0
The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count.
Timepoint [5] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [6] 0 0
Duration of B-cell Depletion (tB-cell) (Days)
Assessment method [6] 0 0
The tB-cell is defined as the time interval over which the B-cell count was \<0.3 cells/uL or the detection limit.
Timepoint [6] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [7] 0 0
Percentage of Participants With CD19+ B-cell Count Recovery
Assessment method [7] 0 0
The percentage of participants with CD19+ B-cell counts which fell to \<50% of Baseline value during treatment and which recovered to =50% of Baseline value at End of Treatment.
Timepoint [7] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [8] 0 0
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)
Assessment method [8] 0 0
The AUC 0-T, B-cell refers to the CD19+ B-cell count over time. It represents the total B-cells over time, from time 0 (the point of drug administration) to the last measured count at time T.
Timepoint [8] 0 0
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [9] 0 0
Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])
Assessment method [9] 0 0
The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit.
Timepoint [9] 0 0
Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [10] 0 0
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
Assessment method [10] 0 0
The percentage change from Baseline in circulating IgM by visit.
Timepoint [10] 0 0
Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25
Secondary outcome [11] 0 0
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit
Assessment method [11] 0 0
ACR20 response: greater than or equal to (=)20% improvement in tender joint count; =20% improvement in swollen joint count; and =20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.
Timepoint [11] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [12] 0 0
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit
Assessment method [12] 0 0
ACR70 response: =70% improvement in tender joint count; =70% improvement in swollen joint count; and =70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participantss who rolled over to the extension study were not included in the non-responder imputation from that point on.
Timepoint [12] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)
Secondary outcome [13] 0 0
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit
Assessment method [13] 0 0
ACR50 response: =50% improvement in tender joint count; =50% improvement in swollen joint count; and =50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.
Timepoint [13] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [14] 0 0
Percentage of Participants by Anti-drug Antibody (ADA) Status
Assessment method [14] 0 0
Presence of anti-rituximab antibodies in blood. Participants with a positive antibody status at any time during the study were defined as having overall positive antibody status; participants with a negative antibody status throughout the study were defined as having overall negative antibody status.
Timepoint [14] 0 0
Days 1 up to Day 169.
Secondary outcome [15] 0 0
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
Assessment method [15] 0 0
Timepoint [15] 0 0
Day 1 up to Day 169
Secondary outcome [16] 0 0
Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)
Assessment method [16] 0 0
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (=)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to =5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.
Timepoint [16] 0 0
Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [17] 0 0
Percent Change From Baseline in DAS28-CRP by Visit
Assessment method [17] 0 0
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (=)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to =5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.
Timepoint [17] 0 0
Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [18] 0 0
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit
Assessment method [18] 0 0
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =5.1 or change from baseline \>0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline \>0.6 and =1.2 with DAS28 \>5.1.
Timepoint [18] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [19] 0 0
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit
Assessment method [19] 0 0
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =5.1 or change from baseline \>0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline \>0.6 and =1.2 with DAS28 \>5.1.
Timepoint [19] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [20] 0 0
Percentage of Participants With No EULAR Response Based on DAS28 by Visit
Assessment method [20] 0 0
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =5.1 or change from baseline \>0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline \>0.6 and =1.2 with DAS28 \>5.1.
Timepoint [20] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [21] 0 0
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit
Assessment method [21] 0 0
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP =3.2 implied low disease activity. p-value of 9999 indicates p-value is not applicable.
Timepoint [21] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [22] 0 0
Percentage of Participants With DAS Remission (DAS <2.6) by Visit
Assessment method [22] 0 0
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission. p-value of 9999 indicates p-value is not applicable.
Timepoint [22] 0 0
Weeks 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [23] 0 0
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit
Assessment method [23] 0 0
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Timepoint [23] 0 0
Baseline, Week 3, 5, 9, 13, 17, 21 and 25
Secondary outcome [24] 0 0
Percent Change From Baseline in HAQ-DI Score by Visit
Assessment method [24] 0 0
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Timepoint [24] 0 0
Baseline, Week 3, 5, 9, 13, 17, 21 and 25

Eligibility
Key inclusion criteria
* Confirmed diagnosis of rheumatoid arthritis
* Meets Class I, II or III of the ACR 1991 Revised Criteria
* RA seropositivity
* Stable dose of methotrexate
* Inadequate response to TNF inhibitors
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any prior treatment with lymphocyte depleting therapies
* History of active TB infection
* Known or screen test positive for specific viruses or indicators of viral infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/05/2014
Sample size
Target
Accrual to date
Final
220
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Rheumatology Research Unit - Maroochydore
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital, Department of Rheumatology - Woodville South
Recruitment hospital [3] 0 0
St. Vincent's Hospital (Melbourne) - Fitzroy
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
03065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oklahoma
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Colombia
State/province [22] 0 0
Antioquia
Country [23] 0 0
Colombia
State/province [23] 0 0
Atlantico
Country [24] 0 0
Colombia
State/province [24] 0 0
Atlántico
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Israel
State/province [26] 0 0
Ramat Gan
Country [27] 0 0
Mexico
State/province [27] 0 0
D.f.
Country [28] 0 0
Mexico
State/province [28] 0 0
Jalisco
Country [29] 0 0
Mexico
State/province [29] 0 0
Durango
Country [30] 0 0
Mexico
State/province [30] 0 0
San Luis Potosi
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Novosibirsk Region
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Tatarstan
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Kemerovo
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Nizhny Novgorod
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Saint-Petersburg
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Samara
Country [37] 0 0
Russian Federation
State/province [37] 0 0
St. Petersburg
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Tomsk
Country [39] 0 0
South Africa
State/province [39] 0 0
Cape Town
Country [40] 0 0
South Africa
State/province [40] 0 0
Kwa-zulu Natal
Country [41] 0 0
United Kingdom
State/province [41] 0 0
UK
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Leeds
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01526057