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Ofatumumab Dose-finding in Relapsing Remitting Multiple Sclerosis (RRMS) Patients (OMS115102)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00640328
First received: March 18, 2008
Last updated: June 19, 2014
Last verified: November 2012
Results First Received: November 1, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Ofatumumab 100
Drug: Ofatumumab 300
Drug: Ofatumumab 700
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In all 3 dose cohorts, participants in the active/placebo group received treatment with ofatumumab during the First Treatment Period and placebo during the Second Treatment Period. Participants in the placebo/active group received treatment with placebo during the First Treatment Period and ofatumumab during the second treatment period.

Reporting Groups
  Description
100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo Ofa was administered as two doses of 100 mg via intravenous (iv) infusions separated by 2 weeks (wks) during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period. An Independent Data Monitoring Committee (IDMC) evaluated the safety data at Week 4 for participants receiving the 100 mg dose before considering progression to the 300 mg dose. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.
300 mg Ofa/Matching Placebo Ofa was administered as two doses of 300 mg via iv infusions separated by 2 wks during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 300 mg dose before considering progression to the 700 mg dose. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.
700 mg Ofa/Matching Placebo Ofa was administered as two doses of 700 mg via iv infusions separated by 2 wks during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.
Matching Placebo/100 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 100 mg via iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 100 mg dose before considering progression to the 300 mg dose. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.
Matching Placebo/300 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 300 mg via iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 300 mg dose before considering progression to the 700 mg dose. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.
Matching Placebo/700 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 700 mg via iv infusions separated by 2 wks during the second 24-wk treatment period. After completing Week 48 of the second treatment period or withdrawing from the study for any reason, participants entered an Individualized Follow-up Period (IFUP) in which they were monitored for B cell and IgG normalization until individual study termination.

Participant Flow for 3 periods

Period 1:   First Treatment Period (Weeks 0-24)
    100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo     300 mg Ofa/Matching Placebo     700 mg Ofa/Matching Placebo     Matching Placebo/100 mg Ofa     Matching Placebo/300 mg Ofa     Matching Placebo/700 mg Ofa  
STARTED     8     11     7     4     4     4  
COMPLETED     8     10     7     4     4     4  
NOT COMPLETED     0     1     0     0     0     0  
Adverse Event                 0                 1                 0                 0                 0                 0  

Period 2:   Second Treatment Period (Weeks 24-48)
    100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo     300 mg Ofa/Matching Placebo     700 mg Ofa/Matching Placebo     Matching Placebo/100 mg Ofa     Matching Placebo/300 mg Ofa     Matching Placebo/700 mg Ofa  
STARTED     8     10     7     4     4     4  
COMPLETED     8     10     7     4     3     4  
NOT COMPLETED     0     0     0     0     1     0  
Adverse Event                 0                 0                 0                 0                 1                 0  

Period 3:   IFUP (Week 48 to Individual Termination)
    100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo     300 mg Ofa/Matching Placebo     700 mg Ofa/Matching Placebo     Matching Placebo/100 mg Ofa     Matching Placebo/300 mg Ofa     Matching Placebo/700 mg Ofa  
STARTED     8     11     7     4     4     4  
COMPLETED     8     10     6     3     4     4  
NOT COMPLETED     0     1     1     1     0     0  
Withdrawal by Subject                 0                 0                 1                 0                 0                 0  
Not Recommended - Informed Consent Form                 0                 1                 0                 1                 0                 0  



  Baseline Characteristics
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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
100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo Ofa was administered as two doses of 100 mg via intravenous (iv) infusions separated by 2 weeks (wks) during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period. An Independent Data Monitoring Committee (IDMC) evaluated the safety data at Week 4 for participants receiving the 100 mg dose before considering progression to the 300 mg dose.
300 mg Ofa/Matching Placebo Ofa was administered as two doses of 300 mg via iv infusions separated by 2 wks during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 300 mg dose before considering progression to the 700 mg dose.
700 mg Ofa/Matching Placebo Ofa was administered as two doses of 700 mg via iv infusions separated by 2 wks during the first 24-wk treatment period. Matching placebo was administered as two iv infusions separated by 2 wks during the second 24-wk treatment period.
Matching Placebo/100 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 100 mg via iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 100 mg dose before considering progression to the 300 mg dose.
Matching Placebo/300 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 300 mg via iv infusions separated by 2 wks during the second 24-wk treatment period. An IDMC evaluated the safety data at Week 4 for participants receiving the 300 mg dose before considering progression to the 700 mg dose.
Matching Placebo/700 mg Ofa Matching placebo was administered as two iv infusions separated by 2 wks during the first 24-wk treatment period. Ofa was administered as two doses of 700 mg via iv infusions separated by 2 wks during the second 24-wk treatment period.
Total Total of all reporting groups

Baseline Measures
    100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo     300 mg Ofa/Matching Placebo     700 mg Ofa/Matching Placebo     Matching Placebo/100 mg Ofa     Matching Placebo/300 mg Ofa     Matching Placebo/700 mg Ofa     Total  
Number of Participants  
[units: participants]
  8     11     7     4     4     4     38  
Age  
[units: Years]
Mean ± Standard Deviation
  38.0  ± 9.0     36.6  ± 7.0     33.7  ± 8.4     37.0  ± 6.5     27.0  ± 2.2     44.0  ± 8.1     36.3  ± 7.9  
Gender  
[units: Participants]
             
Female     6     6     4     3     3     0     22  
Male     2     5     3     1     1     4     16  
Race/Ethnicity, Customized  
[units: participants]
             
White/Caucasian     8     11     7     4     4     4     38  



  Outcome Measures
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1.  Primary:   Number of Participants With Any Adverse Event   [ Time Frame: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

2.  Primary:   Number of Participants With the Indicated Critical Adverse Events (CAEs)   [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

3.  Primary:   Number of Participants With Negative or Unconfirmed Human Anti-human Antibodies (HAHA) in Which Concentrations of Ofa Were Below 500 Nanograms Per Milliliter (ng/ml)   [ Time Frame: Visit 3 (Week 0), Visit 10 (Week 24), Visit 17 (Week 48) or early withdrawal (EW), and Visit 26 (Week 104) ]

4.  Primary:   Number of Participants With Abnormal Physical Examination Findings   [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

5.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelet Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ]

6.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Erythrocyte Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ]

7.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hematocrit at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ]

8.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hemoglobin Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ]

9.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Albumin at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: VIsit 26 (Week 104) ]

10.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Transaminase (ALT) at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

11.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Bicarbonate, Glucose, Potassium, Sodium, and Urea at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

12.  Primary:   Change From Baseline (Week 0 for the FTP,Week 24 for the STP, and Week 0 for the IFUP) in Bilirubin and Creatinine at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

13.  Primary:   Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Immunoglobins at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

14.  Primary:   Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Blood Pressure (BP) at Week 24 (FTP) and Week 48 (STP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ]

15.  Primary:   Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Pulse Rate at Week 24 (FTP) and Week 48 (STP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ]

16.  Primary:   Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Temperature at Week 24 (FTP) and Week 48 (STP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ]

17.  Primary:   Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Complement Activation (CH50) at Week 24 (FTP) and Week 48 (STP)   [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ]

18.  Secondary:   Number of the Indicated Types of Lesions (Ls) Assessed Per Magnetic Resonance Imaging (MRI)   [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ]

19.  Secondary:   Total Volume of T2 Lesions at Week 24 and Week 48   [ Time Frame: Visit 10 (Week 24) and Visit 17 (Week 48) ]

20.  Secondary:   Ofa Drug Concentration After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) Intravenous (i.v.) Infusions   [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ]

21.  Secondary:   The Maximum Observed Plasma Concentration (Cmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions   [ Time Frame: Visit 3 (Week 0), Visit 4, (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ]

22.  Secondary:   The Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point (AUC(0-t)) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions   [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour (hr) after infusion, and 2 hours after infusion. ]

23.  Secondary:   Time to Reach Cmax (Tmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions   [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2),Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ]

24.  Secondary:   Clearance of Ofa Over the Course of Weeks 0-2 and 24-26   [ Time Frame: Weeks 0-2 and 24-26 ]

25.  Secondary:   The Volume of Distribution at Steady State (Vss) of Ofatumumab Over the Course of Weeks 0-2 and 24-26   [ Time Frame: Weeks 0-2 and 24-26 ]

26.  Secondary:   Half Life (t1/2) of Ofatumumab in the Terminal Elimination Phase Over the Course of Weeks 0-2 and 24-26   [ Time Frame: Weeks 0-2 and 24-26 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00640328     History of Changes
Obsolete Identifiers: NCT01526993
Other Study ID Numbers: 115102, GEN414
Study First Received: March 18, 2008
Results First Received: November 1, 2012
Last Updated: June 19, 2014
Health Authority: Poland: Ethics Committees
United Kingdom: Research Ethics Committee
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency
Sweden: Regional Ethical Review Board
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Czech Republic: Ethics Committee
Serbia: ALIMS - Medicines and Medical Devices Agency of Serbia
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Danish Medicines Agency
Serbia: Ethics Committees
Sweden: Medical Products Agency
Czech Republic: State Institute for Drug Control