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Ofatumumab Subcutaneous Administration in Subjects With Relapsing-Remitting Multiple Sclerosis (MIRROR)

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ClinicalTrials.gov Identifier: NCT01457924
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : March 1, 2018
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Ofatumumab 3mg
Drug: Ofatumumab 30mg
Drug: Ofatumumab 60mg
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A participant (par.) completed the study if he/she completed all assessments up to and including the 24 Week Follow-up Phase (FUP) (Week 48) without prematurely discontinuing.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 324 par. with Relapsing-Remitting Multiple Sclerosis (RRMS) were screened and 232 par. were randomized to 24 Week Treatment Phase (Weeks 0-12 were placebo controlled) of the study. A total of 231 par. received at least one dose of double-blind Investigational Product (IP) and were included in the Safety Population.

Reporting Groups
  Description
Placebo/Ofatumumab 3 mg Par. received ofatumumab matching placebo subcutaneous (SC) injection every 4 weeks (q4w) from Week 0 to Week 20, except on Week 12 participants received 3 milligrams (mg) ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 gram (g) and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 3 mg q12w Par. received ofatumumab 3 mg SC injection every 12th week (q12w) on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 30 mg q12w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 60 mg q12w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 60mg q4w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.

Participant Flow for 3 periods

Period 1:   Treatment Phase (Weeks 0-24)
    Placebo/Ofatumumab 3 mg   Ofatumumab 3 mg q12w   Ofatumumab 30 mg q12w   Ofatumumab 60 mg q12w   Ofatumumab 60mg q4w
STARTED   67   34   32   34   64 
Completed to Week 12   65   31   30   33   60 
COMPLETED   64   29   30   33   58 
NOT COMPLETED   3   5   2   1   6 
Adverse Event                0                4                1                0                2 
Physician Decision                0                0                0                0                1 
Lack of Efficacy                1                0                0                0                0 
Protocol Violation                1                0                1                0                0 
Withdrawal by Subject                0                0                0                1                1 
Other-Protocol defined stopping criteria                1                1                0                0                2 

Period 2:   FUP (Weeks 24-48)
    Placebo/Ofatumumab 3 mg   Ofatumumab 3 mg q12w   Ofatumumab 30 mg q12w   Ofatumumab 60 mg q12w   Ofatumumab 60mg q4w
STARTED [1]   66   31   32   33   59 
COMPLETED   63   30   30   32   57 
NOT COMPLETED   3   1   2   1   2 
Adverse Event                0                0                1                0                0 
Physician Decision                1                0                1                0                0 
Lost to Follow-up                0                0                0                1                0 
Withdrawal by Subject                2                1                0                0                2 
[1] A total of 221 par. entered the FUP, including 7 of the 17 par. who were withdrawn before Week 24.

Period 3:   Individualized FUP (Weeks 48+)
    Placebo/Ofatumumab 3 mg   Ofatumumab 3 mg q12w   Ofatumumab 30 mg q12w   Ofatumumab 60 mg q12w   Ofatumumab 60mg q4w
STARTED [1]   16   18   16   20   42 
COMPLETED   11   14   12   15   36 
NOT COMPLETED   5   4   4   5   6 
Lost to Follow-up                1                0                1                0                0 
Other-Protocol defined stopping criteria                3                4                2                3                5 
Withdrawal by Subject                1                0                1                2                1 
[1] Par. whose CD19+ B lymphocyte counts had not recovered to lower limit of normal entered IFU phase.



  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.
No text entered.

Reporting Groups
  Description
Placebo/Ofatumumab 3 mg Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 3 mg q12w Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 30 mg q12w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 60 mg q12w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Ofatumumab 60mg q4w Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Total Total of all reporting groups

Baseline Measures
   Placebo/Ofatumumab 3 mg   Ofatumumab 3 mg q12w   Ofatumumab 30 mg q12w   Ofatumumab 60 mg q12w   Ofatumumab 60mg q4w   Total 
Overall Participants Analyzed 
[Units: Participants]
 67   34   32   34   64   231 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.7  (9.38)   38.1  (8.29)   37.2  (10.04)   37.3  (9.67)   36.2  (9.57)   37.2  (9.36) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
           
Female      46  68.7%      22  64.7%      24  75.0%      22  64.7%      41  64.1%      155  67.1% 
Male      21  31.3%      12  35.3%      8  25.0%      12  35.3%      23  35.9%      76  32.9% 
Race/Ethnicity, Customized 
[Units: Participants]
           
African American/African Heritage   1   0   0   0   1   2 
Asian - East Asian Heritage   0   0   1   0   0   1 
White - White/Caucasian/European Heritage   65   34   31   34   61   225 
Mixed Race   1   0   0   0   2   3 


  Outcome Measures

1.  Primary:   Cumulative Number of New Gadolinium-enhancing (GdE) T1 Lesions at Week 12   [ Time Frame: Week 12 ]

2.  Secondary:   Cumulative Number of New GdE T1 Lesions at Week 24   [ Time Frame: Week 24 ]

3.  Secondary:   Change From Baseline in Brain Volume at Week 24 and Week 48   [ Time Frame: Baseline (Week 0), Week 24 and Week 48 ]

4.  Secondary:   Cumulative Number of Persistent GdE Brain Lesions on T1-weighted MRI at Week 12   [ Time Frame: Week 12 ]

5.  Secondary:   Cumulative Number of All (New Plus Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12   [ Time Frame: Week 12 ]

6.  Secondary:   Total Volume of New GdE Brain Lesions on T1-weighted MRI at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Total Volume of All (New and Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12   [ Time Frame: Week 12 ]

8.  Secondary:   Cumulative Number of New and Newly Enlarging GdE T2 Lesions at Week 12   [ Time Frame: Week 12 ]

9.  Secondary:   Total Volume of New and/or Newly Enlarging T2 Lesions at Week 12   [ Time Frame: Week 12 ]

10.  Secondary:   Cumulative Number of New T1 Hypointense Lesions at Week 24 and Week 48   [ Time Frame: Week 24 and Week 48 ]

11.  Secondary:   Cumulative Volume of New T1 Hypointense Lesions at Week 24 and Week 48   [ Time Frame: Baseline, Week 24 and Week 48 ]


  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 incorrect exclusion of one par. from ITT pop. at Wk 24 was not considered to impact overall interpretation of data: no updates were made to source tables/analyses. This par. had withdrawn early, having never received a dose of active study drug.


  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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01457924     History of Changes
Other Study ID Numbers: 112831
First Submitted: October 20, 2011
First Posted: October 24, 2011
Results First Submitted: March 21, 2017
Results First Posted: March 1, 2018
Last Update Posted: June 5, 2018