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Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT01682512
Recruitment Status : Terminated (substance discontinued)
First Posted : September 11, 2012
Results First Posted : January 30, 2018
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: BI 695500
Drug: Rituxan®
Drug: MabThera®

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled into this multi-center, randomized, double-blind, parallel arm, multiple dose, active comparator 2 part trial from 27 September 2017. Trial was terminated on 3 September 2015 and last subject completed 28 October 2016.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
509 subjects were screened for eligibility to participate in the trial. 293 subjects met all inclusion and exclusion criteria and were randomised to receive treatment. 6 subjects were included in an open-label safety run-in prior to randomisation in Part-I.

Reporting Groups
  Description
BI 695500 Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.
Rituxan® Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.
MabThera® Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.

Participant Flow:   Overall Study
    BI 695500   Rituxan®   MabThera®
STARTED   116   111   66 
Randomized in Part-I   66   65   66 
Randomized in Part-II   50   46   0 
COMPLETED   44   40   48 
NOT COMPLETED   72   71   18 
Adverse Event                6                5                2 
Withdrawal by Subject                2                6                3 
Physician Decision                0                2                0 
Study terminated by sponsor                46                43                0 
Lost to Follow-up                3                0                2 
Protocol Violation                2                3                2 
Primary lack of efficacy                10                7                7 
Secondary lack of efficacy                1                1                0 
Other than stated above                2                4                2 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety randomized analysis set (SAFR) contained all randomized subjects who received at least one dose of trial medication and subjects were classified according to treatment received.

Reporting Groups
  Description
BI 695500 Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.
Rituxan® Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.
MabThera® Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.
Total Total of all reporting groups

Baseline Measures
   BI 695500   Rituxan®   MabThera®   Total 
Overall Participants Analyzed 
[Units: Participants]
 116   110   65   291 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.7  (10.46)   54.0  (11.10)   54.8  (12.22)   54.5  (11.08) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      94  81.0%      96  87.3%      52  80.0%      242  83.2% 
Male      22  19.0%      14  12.7%      13  20.0%      49  16.8% 


  Outcome Measures

1.  Primary:   Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I   [ Time Frame: Baseline and Week 24 ]

2.  Primary:   PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)   [ Time Frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion. ]

3.  Primary:   PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)   [ Time Frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion. ]

4.  Primary:   PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)   [ Time Frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion. ]

5.  Primary:   PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)   [ Time Frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion. ]

6.  Secondary:   Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II   [ Time Frame: Week 24 ]

7.  Secondary:   PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)   [ Time Frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study program was terminated and this study was discontinued on 3 September 2015. As a result no patients receiving study treatment in Part II of the study reached Week 24, and no conclusions regarding the efficacy of BI 695500 can be made.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com



Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01682512     History of Changes
Other Study ID Numbers: 1301.1
2011-002894-48 ( EudraCT Number )
First Submitted: August 10, 2012
First Posted: September 11, 2012
Results First Submitted: October 24, 2017
Results First Posted: January 30, 2018
Last Update Posted: January 30, 2018