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TerminatedNCT01955733Updated Jan 18, 2018Results posted

Safety and Efficacy of BI 695500 in Patients With Moderately to Severely Active Rheumatoid Arthritis

A Phase 3 interventional study of BI 695500 in Arthritis, Rheumatoid, sponsored by Boehringer Ingelheim. Terminated at 43 sites in 9 countries. Open to participants aged 18 Years to 82 Years. Per ClinicalTrials.gov, last updated 2018-01-18.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Why this study was terminated
Substance discontinued

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled May 2013, registered Sep 2013).
Phase
Phase 3
Study type
Interventional
Enrollment
91
Allocation
Not applicable
Ages
18 Years to 82 Years
Sex
All
01

Study summary

The primary objective of this trial is to evaluate the long-term safety of BI 695500 in adult patients with moderately to severely active rheumatoid arthritis (RA) who have successfully completed treatment in Trial 1301.1.

02

Conditions studied

  • Arthritis, Rheumatoid
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 318 are open to participants now.

This study's enrollment of 91 is close to the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 82 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Must give written informed consent and be willing to follow this Clinical Trial Protocol.
  2. Male or female patients, with moderately to severely active RA who have previously participated in the double-blind randomized clinical Trial 1301.1.

  3. Current treatment for RA on an outpatient basis:

    1. Patients must continue to receive and tolerate oral or parenteral methotrexate (MTX) therapy at a dose of 15-25 mg per week (dose may be as low as 10 mg per week if the patient is unable to tolerate a higher dose).
    2. Patients must be willing to receive oral folic acid (at least 5 mg/week or as per local practice) or folinic acid (at least 1 mg per week or as per local practice) or equivalent during the entire trial.
    3. If receiving current treatment with oral corticosteroids (other than intra-articular or parenteral), the dose must not exceed 10 mg/day prednisolone or equivalent. During the 4 weeks prior to Baseline (Day 1) the dose must remain stable.
    4. Intra-articular and parenteral corticosteroids are not permitted throughout the trial, with the exception of IV administration of 100 mg methylprednisolone 30 to 60 minutes prior to each infusion as part of the trial procedures.
    5. Any concomitant non-steroidal anti-inflammatory drugs (NSAIDs) must be stable throughout the trial.
    6. Patients may be taking oral hydroxychloroquine provided that the dose is not greater than 400 mg/day, or chloroquine provided that the dose is not greater than 250 mg/day. These doses must have been stable for a minimum of 12 weeks prior to Day 1. The hydroxychloroquine or chloroquine treatment will need to be continued at a stable dose with the same formulation until the end of the trial.
  4. For participants of reproductive potential (males and females), use of a medically acceptable method of contraception during the trial, i.e., a combination of 2 forms of effective contraception (defined as hormonal contraception, intrauterine device, condom with spermicide, etc.). Females of childbearing potential must also agree to use an acceptable method of contraception (see above) for 12 months following completion or discontinuation from the trial medication.

Exclusion criteria

Exclusion criteria:

  1. Patients receiving current treatment with corticosteroids must not be receiving a dose exceeding 10 mg/day prednisone or equivalent.
  2. Serious underlying medical conditions, which, per the investigator¿s discretion, could impair the ability of the patient to participate in the trial (including but not limited to ongoing severe infection, severe immunosuppression, severe heart failure, uncontrolled hypertension, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
  3. Pregnancy or breast feeding. For women of childbearing potential, a positive serum pregnancy test at the Screening Visit.
  4. Patients who have significant cardiac disease, including but not limited to congestive heart failure of Class III or IV of the New York Heart Association (NYHA) classification; uncontrolled angina or arrhythmia; any uncontrolled or severe cardiovascular or cerebrovascular disease; or uncontrolled hypertension.
  5. Treatment with IV or intramuscular corticosteroids. The only exception will be the administration of 100 mg IV methylprednisolone 30 to 60 minutes before each infusion as part of the trial procedures.
  6. Any condition or treatment (including biologic therapies) that, in the opinion of the investigator, may place the patient at unacceptable risk during the trial.
  7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times upper limit of normal (ULN).
  8. Hemoglobin \<8.0 g/dL.
  9. Levels of Immunoglobulin G(IgG) \<5.0 g/L.
  10. Absolute neutrophil count \<1500/µL.
  11. Platelet count \<75000/µL.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
91 participants (actual)

Study arms

  • Experimental
    BI 695500

    BI 695500, Two infusions separated by 2 weeks, Intravenous infusion

    Drug: BI 695500

Interventions

  • DrugBI 695500
06

What researchers measure

Primary outcomes

  1. The Percentage of Patients With Drug Related Adverse Events During the Treatment Phase

    This outcome measure presents percentage of patients with drug related adverse events during the treatment phase. Treatment Emergent Adverse Events (TEAEs) were defined as Adverse Events (AEs) that started or worsened in severity on or after the first dose of trial medication in this extension study \[1301.4\] and prior to the last date of trial medication + 180 days \[inclusive\]. Drug-related events were those considered by the investigator to have a causal relationship to trial medication.

    Time frame: Week 48

Secondary outcomes

  1. Change From Baseline in Clinical Trial 1301.1 in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 of Clinical Trial 1301.4

    DAS-28 (ESR)\*\* is an index containing a 28-joint count for tenderness (TJC28), 28 joint count for swelling (SJC28), natural logarithm of ESR (inflammation) (Ln\[ESR\]) and a general health component (GH) which is the patient's global assessment of disease activity and was used to describe the severity of RA. The DAS28 (ESR) Score is calculated as: DAS28(ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.70\*ln(ESR) + 0.014\*(GH). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2. The mean change from baseline (in clinical trial 1301.1) at Week 48 in the DAS28 (ESR) score is presented.

    Time frame: Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.

  2. The Percentage of Patients Meeting the ACR20 [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

    A subject has an ACR20 response if all of the following occur: * a \> 20% improvement in the swollen joint count (66 joints) * a \> 20% improvement in the tender joint count (68 joints) * a \> 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (CRP). The number of subjects meeting the ACR20 response criteria at Week 48 is presented.

    Time frame: Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.

  3. The Percentage of Patients Who Meet the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Definition of Remission [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

    To meet the ACR/EULAR Remission criteria\*, the subject needed to satisfy the following criteria: * TCJ (68 joints) \< 1 * SJC (66 joints) \< 1 * CRP \< 1 milligrams per decilitre * patient global assessment \< 10. The patient global assessment for the definition of ACR/EULAR Remission was defined with a visual analog scale in millimetres (0-100).\*\* The number of subjects meeting the ACR/EULAR Remission definition at Week 48 is presented.

    Time frame: Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.

  4. The Percentage of Patients Who Meet the EULAR Response [Good Response, Moderate Response, or no Response] [Based on DAS28 Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

    This outcome measure presents percentage of patients who meet the EULAR response \[good response, moderate response, or no response\] \[based on DAS28 improvement since baseline in trial 1301.1\] at Week 48 of trial 1301.4.

    Time frame: Week 48

07

Results

Posted Jan 18, 2018
Limitations and caveats
Further development of BI 695500 has been stopped and the program was therefore prematurely discontinued on 03Sep2015. The decision was made by the Sponsor based on a strategic review of company's product portfolio and not due to any safety concern.

Participant flow

Period 1
Participant flow — Period 1
MilestoneBI 695500Rituxan From 1301.1MabThera From 1301.1
Started332929
Completed322929
Not completed100
Withdrew: Lost to follow-up100
Period 2
Participant flow — Period 2
MilestoneBI 695500Rituxan From 1301.1MabThera From 1301.1
Started322929
Completed20108
Not completed121921
Withdrew: Adverse event100
Withdrew: Physician decision001
Withdrew: Withdrawal by subject132
Withdrew: Study terminated by sponsor81416
Withdrew: Lost to follow-up200
Withdrew: Other not defined above022

Outcome measures

PrimaryThe Percentage of Patients With Drug Related Adverse Events During the Treatment Phase

This outcome measure presents percentage of patients with drug related adverse events during the treatment phase. Treatment Emergent Adverse Events (TEAEs) were defined as Adverse Events (AEs) that started or worsened in severity on or after the first dose of trial medication in this extension study \[1301.4\] and prior to the last date of trial medication + 180 days \[inclusive\]. Drug-related events were those considered by the investigator to have a causal relationship to trial medication.

Time frame:
Week 48
Reported as:
Number · Percentage of patients
The Percentage of Patients With Drug Related Adverse Events During the Treatment Phase
Percentage of patientsBI 695500Rituxan From 1301.1MabThera From 1301.1
The Percentage of Patients With Drug Related Adverse Events During the Treatment Phase16.76.93.4
SecondaryChange From Baseline in Clinical Trial 1301.1 in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 of Clinical Trial 1301.4

DAS-28 (ESR)\*\* is an index containing a 28-joint count for tenderness (TJC28), 28 joint count for swelling (SJC28), natural logarithm of ESR (inflammation) (Ln\[ESR\]) and a general health component (GH) which is the patient's global assessment of disease activity and was used to describe the severity of RA. The DAS28 (ESR) Score is calculated as: DAS28(ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.70\*ln(ESR) + 0.014\*(GH). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2. The mean change from baseline (in clinical trial 1301.1) at Week 48 in the DAS28 (ESR) score is presented.

Time frame:
Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.
Reported as:
Least squares mean · Units on Scale
Change From Baseline in Clinical Trial 1301.1 in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 of Clinical Trial 1301.4
Units on ScaleBI 695500Rituxan From 1301.1MabThera From 1301.1
Change From Baseline in Clinical Trial 1301.1 in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 of Clinical Trial 1301.4-2.0 (-2.70 to -1.33)-2.0 (-2.66 to -1.38)-1.6 (-2.42 to -0.88)
SecondaryThe Percentage of Patients Meeting the ACR20 [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

A subject has an ACR20 response if all of the following occur: * a \> 20% improvement in the swollen joint count (66 joints) * a \> 20% improvement in the tender joint count (68 joints) * a \> 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (CRP). The number of subjects meeting the ACR20 response criteria at Week 48 is presented.

Time frame:
Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.
Reported as:
Number · Percentage of patients
The Percentage of Patients Meeting the ACR20 [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4
Percentage of patientsBI 695500Rituxan From 1301.1MabThera From 1301.1
The Percentage of Patients Meeting the ACR20 [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.43.74.34.0
SecondaryThe Percentage of Patients Who Meet the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Definition of Remission [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

To meet the ACR/EULAR Remission criteria\*, the subject needed to satisfy the following criteria: * TCJ (68 joints) \< 1 * SJC (66 joints) \< 1 * CRP \< 1 milligrams per decilitre * patient global assessment \< 10. The patient global assessment for the definition of ACR/EULAR Remission was defined with a visual analog scale in millimetres (0-100).\*\* The number of subjects meeting the ACR/EULAR Remission definition at Week 48 is presented.

Time frame:
Baseline in clinical trial 1301.1 up to Week 48 in clinical trial 1301.4.
Reported as:
Number · Percentage of patients
The Percentage of Patients Who Meet the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Definition of Remission [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4
Percentage of patientsBI 695500Rituxan From 1301.1MabThera From 1301.1
The Percentage of Patients Who Meet the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Definition of Remission [Based on Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.40.00.00.0
SecondaryThe Percentage of Patients Who Meet the EULAR Response [Good Response, Moderate Response, or no Response] [Based on DAS28 Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4

This outcome measure presents percentage of patients who meet the EULAR response \[good response, moderate response, or no response\] \[based on DAS28 improvement since baseline in trial 1301.1\] at Week 48 of trial 1301.4.

Time frame:
Week 48
Reported as:
Number · Percentage of patients
The Percentage of Patients Who Meet the EULAR Response [Good Response, Moderate Response, or no Response] [Based on DAS28 Improvement Since Baseline in Trial 1301.1] at Week 48 of Trial 1301.4
Percentage of patientsBI 695500Rituxan From 1301.1MabThera From 1301.1
Good response0.00.00.0
Moderate response3.37.70.0
No response13.315.414.3
Missing43.315.414.3

Adverse events

Collected over TEAEs were collected from the first dose of study medication in this extension study [1301.4] and prior to the last date of study medication + 6 months [180 days].. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BI 695500—0/30 (0%)7/30 (23.3%)
Rituxan From 1301.1—2/29 (6.9%)8/29 (27.6%)
MabThera From 1301.1—2/29 (6.9%)9/29 (31%)
Most frequent serious events
Most frequent serious events
EventBI 695500Rituxan From 1301.1MabThera From 1301.1
CellulitisInfections and infestations0/300/292/29
Femur fractureInjury, poisoning and procedural complications0/301/290/29
HypoglycaemiaMetabolism and nutrition disorders0/300/291/29
Metabolic acidosisMetabolism and nutrition disorders0/300/291/29
Cerebral microangiopathyNervous system disorders0/301/290/29
Metabolic encephalopathyNervous system disorders0/300/291/29
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/301/290/29
Deep vein thrombosisVascular disorders0/301/290/29
Most frequent other events
Most frequent other events
EventBI 695500Rituxan From 1301.1MabThera From 1301.1
Urinary tract infectionInfections and infestations3/302/294/29
Viral upper respiratory tract infectionInfections and infestations3/302/292/29
SinusitisInfections and infestations1/301/292/29
HypercholesterolaemiaMetabolism and nutrition disorders1/302/291/29
PharyngitisInfections and infestations0/300/292/29
InsomniaPsychiatric disorders0/302/290/29
CoughRespiratory, thoracic and mediastinal disorders2/301/290/29

Baseline characteristics

Safety Randomized Analysis Set \[SAFRD\]: All subjects randomized in 1301.1 \[excluding open-label safety run-in subjects of trial 1301.1\] who receive at least one dose of trial medication and subjects will be classified according to treatment received in trial 1301.1. 2 subjects from 1301.1 safety run-in also received treatment in 1301.4, thus 88.

Age, Continuous
Age, Continuous(Years)BI 695500Rituxan From 1301.1MabThera From 1301.1Total
Mean54.6 ± 11.2356.3 ± 11.0256.8 ± 8.9555.9 ± 10.38
Sex: Female, Male
Sex: Female, Male(Participants)BI 695500Rituxan From 1301.1MabThera From 1301.1Total
Female21242267
Male95721
08

Study locations

43 sites
  • 1301.4.5585 Boehringer Ingelheim Investigational Site
    Birmingham, Alabama, United States
  • 1301.4.5727 Boehringer Ingelheim Investigational Site
    Glendale, Arizona, United States
  • 1301.4.5725 Boehringer Ingelheim Investigational Site
    Phoenix, Arizona, United States
  • 1301.4.5761 Boehringer Ingelheim Investigational Site
    Little Rock, Arkansas, United States
  • 1301.4.5765 Boehringer Ingelheim Investigational Site
    El Cajon, California, United States
  • 1301.4.5553 Boehringer Ingelheim Investigational Site
    Lakewood, California, United States
  • 1301.4.5527 Boehringer Ingelheim Investigational Site
    Long Beach, California, United States
  • 1301.4.5771 Boehringer Ingelheim Investigational Site
    San Diego, California, United States
  • 1301.4.5797 Boehringer Ingelheim Investigational Site
    Santa Maria, California, United States
  • 1301.4.5807 Boehringer Ingelheim Investigational Site
    Upland, California, United States
  • 1301.4.5809 Boehringer Ingelheim Investigational Site
    Pembroke Pines, Florida, United States
  • 1301.4.5567 Boehringer Ingelheim Investigational Site
    Tampa, Florida, United States
  • 1301.4.5561 Boehringer Ingelheim Investigational Site
    Chicago, Illinois, United States
  • 1301.4.5721 Boehringer Ingelheim Investigational Site
    Columbia, Maryland, United States
  • 1301.4.5811 Boehringer Ingelheim Investigational Site
    Cumberland, Maryland, United States
  • 1301.4.5507 Boehringer Ingelheim Investigational Site
    Worcester, Massachusetts, United States
  • 1301.4.5715 Boehringer Ingelheim Investigational Site
    Grand Rapids, Michigan, United States
  • 1301.4.5787 Boehringer Ingelheim Investigational Site
    Omaha, Nebraska, United States
  • 1301.4.5525 Boehringer Ingelheim Investigational Site
    Toms River, New Jersey, United States
  • 1301.4.5779 Boehringer Ingelheim Investigational Site
    Brooklyn, New York, United States
  • 1301.4.5717 Boehringer Ingelheim Investigational Site
    Charlotte, North Carolina, United States
  • 1301.4.5801 Boehringer Ingelheim Investigational Site
    Dayton, Ohio, United States
  • 1301.4.5549 Boehringer Ingelheim Investigational Site
    Memphis, Tennessee, United States
  • 1301.4.5729 Boehringer Ingelheim Investigational Site
    Nashville, Tennessee, United States
  • 1301.4.5757 Boehringer Ingelheim Investigational Site
    Carrollton, Texas, United States
  • 1301.4.5789 Boehringer Ingelheim Investigational Site
    Corpus Christi, Texas, United States
  • 1301.4.5705 Boehringer Ingelheim Investigational Site
    Houston, Texas, United States
  • 1301.4.5597 Boehringer Ingelheim Investigational Site
    McKinney, Texas, United States
  • 1301.4.5795 Boehringer Ingelheim Investigational Site
    Beckley, West Virginia, United States
  • 1301.4.0303 Boehringer Ingelheim Investigational Site
    Kortrijk, Belgium
  • 1301.4.0609 Boehringer Ingelheim Investigational Site
    Plovdiv, Bulgaria
  • 1301.4.1705 Boehringer Ingelheim Investigational Site
    Magdeburg, Germany
  • 1301.4.1807 Boehringer Ingelheim Investigational Site
    Athens, Greece
  • 1301.4.3305 Boehringer Ingelheim Investigational Site
    Sneek, Netherlands
  • 1301.4.3909 Boehringer Ingelheim Investigational Site
    Bialystok, Poland
  • 1301.4.3907 Boehringer Ingelheim Investigational Site
    Bydgoszcz, Poland
  • 1301.4.3915 Boehringer Ingelheim Investigational Site
    Krakow, Poland
  • 1301.4.3919 Boehringer Ingelheim Investigational Site
    Warszawa, Poland
  • 1301.4.3917 Boehringer Ingelheim Investigational Site
    Wroclaw, Poland
  • 1301.4.4013 Boehringer Ingelheim Investigational Site
    Amadora, Portugal
  • 1301.4.4007 Boehringer Ingelheim Investigational Site
    Lisboa, Portugal
  • 1301.4.4809 Boehringer Ingelheim Investigational Site
    Sevilla, Spain
  • 1301.4.4813 Boehringer Ingelheim Investigational Site
    Sevilla, Spain
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 18, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01955733
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Oct 7, 2013
Start date
May 31, 2013
Primary completion
Nov 18, 2015
Completion
Nov 7, 2016
Results posted
Jan 18, 2018
Last update
Jan 18, 2018

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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