Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01920477
• Collaborator: (none)
• Enrollment: 35
• Locations: 16
• Arms: 2
• Actual Duration (Months): 53
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Pemphigus vulgaris (PV) is a rare, chronic, debilitating, and potentially life-threatening autoimmune disorder that is characterized by mucocutaneous blisters. Ofatumumab is a novel monoclonal antibody (mAb) that specifically binds to the human CD20 antigen, which is expressed only in B lymphocytes.

The purpose of this study was to evaluate the efficacy, tolerability, and safety of ofatumumab injection for subcutaneous use (ofatumumab SC) 20 milligrams (mg) administered once in every 4 weeks, (with an additional 20 mg loading dose [i.e. 40 mg total] at both Week 0 and Week 4) in subjects with PV. It was anticipated that with sustained B-cell depletion in the presence of ofatumumab SC, and the resultant reduction of pathogenic anti Dsg (desmoglein) autoantibodies in PV, that clinical remission of the disease would result.

Condition or Disease	Intervention/Treatment	Phase
Pemphigus Vulgaris	Biological: Ofatumumab; Biological: Placebo	Phase 3

Detailed Description

Novartis terminated the development of the PV program and this study was terminated for non-safety reasons

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: OPV116910: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Ofatumumab Injection for Subcutaneous Use in Subjects With Pemphigus Vulgaris
• Actual Study Start Date: Aug 13, 2013
• Actual Primary Completion Date: Apr 13, 2016
• Actual Study Completion Date: Jan 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab Subject received subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Biological: Ofatumumab; Ofatumumab (human monoclonal antibody) was provided in prefilled glass syringes initial syringes contained 0.6ml (60mg) of concentration 100 mg/m: drug product subsequently modified to 0.4 mL (20mg) concentration (50mg/ML) drug product
Placebo Comparator: Placebo Subject received subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.	Biological: Placebo; Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy [Baseline up to approximately 60 weeks]

   Sustained remission = time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintenance of a dose <=10 mg/day with no new or nonhealing lesions for >=8 weeks and maintenance of the status until Week 60.

2. Duration of Remission on Minimal Steroid Therapy [Baseline up to approximately 60 weeks]

   Sum of all periods of absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day up to Week 60 was assessed.

Secondary Outcome Measures

1. Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 [Week 60]

   Percentage of subjects who achieved absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day for > or = 8 weeks at Week 60 was assessed. Time to remission was not estimable.

2. Time to Remission While on Minimal Steroid Therapy by Week 60. [Baseline up to approximately 60 weeks]

   Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintained dose at <=10 mg/day with no new or nonhealing lesions for >=8 weeks by Week 60 was assessed

3. Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60 [Baseline up to approximately 60 weeks]

   Percentage of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 were to be assessed. All subjects remained on prednisone/prednisolone so this endpoint could not be analyzed.Time to remission off steroid therapy also could not be analyzed

4. Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. [Baseline up to approximately 60 weeks]

   Number of days a subject maintained minimal steroid therapy (an oral prednisone/prednisolone dose of ≤10 mg/day in the absence of new or nonhealing lesions) by Week 60.

5. Time to Initial Flare/Relapse by Week 60 [Baseline up to approximately 60 weeks]

   Time from randomization to the time of appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed

6. Percentage of Participants With no Flare/Relapse by Week 60 [Baseline up to approximately 60 weeks]

   Percentage of participants achieving absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day and did not subsequently have a appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed

7. Plasma Trough Concentrations of Ofatumumab [4 hours post baseline, Days 1-4,7,14, Weeks 4,8,12,16,20,24,36,48,52,56, up to approximately 60 weeks]

   Only plasma (trough) concentrations of ofatumumab were presented

8. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A [Baseline up to approximately 60 weeks]

   Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

9. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G [Baseline up to approximately 60 weeks]

   Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

10. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M [Baseline up to approximately 60 weeks]

    Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

11. Largest Mean Decrease From Baseline for Immunoglobulin A, G and M [Baseline up to approximately 60 weeks]

    Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

12. Change From Baseline for CD19+ B Cell Count [Baseline up to approximately 60 weeks]

    CD19+ B cell count will be performed using Flow Cytometry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

• Adults (18 through 70 years of age) with clinically-documented diagnosis of PV for >2 months and <10 years.

• History of biopsy consistent with PV (Hematoxylin and Eosin staining and direct immunofluorescence). If no history, a biopsy may be performed during the Screening Period.

• At least 1 previous episode of a failed steroid taper (ie, disease flare/relapse) at a prednisone/prednisolone dose >10 mg/day. The following criteria must have been met as evidence of disease severity at the time of the failed steroid taper: a) A Pemphigus Severity of Clinical Disease score of moderate (2) or severe (3) (may be historical/retrospective assessment). b) Required a treatment change at the time of the failed steroid taper of at least one of the following: i) A steroid increase to

=20 mg/day OR ii) The addition of immunosuppressive/immunomodulatory agent/treatment OR iii) A dose increase of immunosuppressive/immunomodulatory agent/treatment

• Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated antiDsg3 antibodies).

• Has initiated and received a stable dose of prednisone/prednisolone from a minimum of 20 mg/day (example: 0.25 mg/kg/day for an 80 kg person) up to a maximum of 120 mg/day or 1.5 mg/kg/day (whichever is higher) for >=2 weeks prior to randomization.

• Has exhibited PV disease control, defined as no new lesions for >=2 weeks.

• A female subject is eligible to enter the study if she: Is of non-child bearing potential, who is either surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or post-hysterectomy) or is postmenopausal without menses for >2 years. Women who are <2 years postmenopausal are required to have menopausal status confirmed by follicle-stimulating hormone (FSH) and estradiol levels at the screening evaluation. If FSH and estradiol levels do not provide confirmation of menopause, subject will be considered to be of childbearing potential.

Exclusion Criteria:

• Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris).

• Past or current history of hypersensitivity to components of the investigational product or medically significant adverse effects (including allergic reactions) from cetirizine (or antihistamine equivalent) or paracetamol/acetaminophen.

• Prior treatment with rituximab without achieving disease control within 6 months of initiating rituximab dosing.

• Prior treatment with immunosuppressant or immunomodulation agents within the protocol specified periods

• Evidence or history of clinically significant infections

For Japan: Evidence or history of clinically significant infection or medical condition including: Pneumocystis pneumonia or interstitial pneumonia

• Past or current malignancy, except for cervical carcinoma Stage 1B or less, noninvasive basal cell and squamous cell skin carcinoma and cancer diagnoses with a duration of complete response (remission) >5 years

• Significant concurrent, uncontrolled medical condition that could affect the subject's safety, impair the subject's reliable participation in the study, impair the evaluation of endpoints, or necessitate the use of medication not allowed by the protocol. This includes subjects who require any systemic steroid treatment for a concurrent medical condition (other than pemphigus vulgaris).

• Use of an investigational drug or other experimental therapy within 4 weeks, 5 pharmacokinetic half-lives, or the duration of biological effect (whichever is longer) prior to Screening.

• Electrocardiogram (ECG) showing a clinically significant abnormality or showing a QTc interval ≥450 msec (≥480 msec for subjects with a bundle branch block)

• Woman who is breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigational Site	Los Angeles	California	United States	90045
2	Novartis Investigational Site	Atlanta	Georgia	United States	30322
3	Novartis Investigational Site	Ann Arbor	Michigan	United States	48103
4	Novartis Investigational Site	Buffalo	New York	United States	14203
5	Novartis Investigational Site	Durham	North Carolina	United States	27710
6	Novartis Investigational Site	Pittsburgh	Pennsylvania	United States	15213
7	Novartis Investigational Site	Salt Lake City	Utah	United States	84132
8	Novartis Investigational Site	East Melbourne	Victoria	Australia	3002
9	Novartis Investigational Site	Melbourne	Victoria	Australia	3050
10	Novartis Investigational Site	Thessalonica		Greece	54643
11	Novartis Investigational Site	Ramat-Gan		Israel	52621
12	Novartis Investigational Site	Tel Aviv		Israel	64239
13	Novartis Investigational Site	Milano	Lombardia	Italy	20122
14	Novartis Investigational Site	Tokyo		Japan	160-8582
15	Novartis Investigational Site	Warszawa		Poland	02-008
16	Novartis Investigational Site	Cluj-Napoca		Romania	400006

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Sep 5, 2016
• Statistical Analysis Plan - Mar 29, 2018

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01920477
• Other Study ID Numbers: 116910
• First Posted: Aug 12, 2013
• Last Update Posted: Jun 6, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Pemphigus; MAB; autoimmune disorder; human CD20 antigen; subcutaneous; vulgaris; Phase 3; monoclonal antibody; ofatumumab; PV; rare disease; OMB157; adult
• Additional relevant MeSH terms: Pemphigus; Ofatumumab

Study Results

Participant Flow

Pre-assignment Detail	Sixty-nine subjects were screened.

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Period Title: Overall Study
STARTED	17	18
Requiried Individualized Follow-up	1	0
COMPLETED	2	1
NOT COMPLETED	15	17

Baseline Characteristics

Arm/Group Title	Ofatumumab	Placebo	Total
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.	Total of all reporting groups
Overall Participants	17	18	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.6 (8.70)	47.1 (11.20)	48.3 (10.0)
Sex: Female, Male (Count of Participants)
Female	10 58.8%	8 44.4%	18 51.4%
Male	7 41.2%	10 55.6%	17 48.6%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	1 5.9%	0 0%	1 2.9%
American Indian or Alaskan Native	1 5.9%	2 11.1%	3 8.6%
Asian - East Asian Heritage	2 11.8%	0 0%	2 5.7%
Asian - Japanese Heritage	1 5.9%	1 5.6%	2 5.7%
White - Arabic/North African Heritage	2 11.8%	1 5.6%	3 8.6%
White - White/ Caucasian/ European Heritage	10 58.8%	14 77.8%	24 68.6%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
Description	Sustained remission = time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintenance of a dose <=10 mg/day with no new or nonhealing lesions for >=8 weeks and maintenance of the status until Week 60.
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Number [participants]	0 0%	0 0%

2. Primary Outcome

Title	Duration of Remission on Minimal Steroid Therapy
Description	Sum of all periods of absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day up to Week 60 was assessed.
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	3	1
Mean (Standard Deviation) [days]	168.0 (73.33)	122.0 (NA)

3. Secondary Outcome

Title	Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60
Description	Percentage of subjects who achieved absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day for > or = 8 weeks at Week 60 was assessed. Time to remission was not estimable.
Time Frame	Week 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Number [percentage of participants]	17.6 103.5%	5.6 31.1%

4. Secondary Outcome

Title	Time to Remission While on Minimal Steroid Therapy by Week 60.
Description	Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintained dose at <=10 mg/day with no new or nonhealing lesions for >=8 weeks by Week 60 was assessed
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Median (95% Confidence Interval) [days]	NA	NA

5. Secondary Outcome

Title	Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60
Description	Percentage of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 were to be assessed. All subjects remained on prednisone/prednisolone so this endpoint could not be analyzed.Time to remission off steroid therapy also could not be analyzed
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

All participants remained on steroid therapy

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60.
Description	Number of days a subject maintained minimal steroid therapy (an oral prednisone/prednisolone dose of ≤10 mg/day in the absence of new or nonhealing lesions) by Week 60.
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	3	1
Mean (Standard Deviation) [days]	168 (73.33)	122.0 (NA)

7. Secondary Outcome

Title	Time to Initial Flare/Relapse by Week 60
Description	Time from randomization to the time of appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	2	8
Median (95% Confidence Interval) [days]	448	169.0

8. Secondary Outcome

Title	Percentage of Participants With no Flare/Relapse by Week 60
Description	Percentage of participants achieving absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day and did not subsequently have a appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Week 2 no flare	100.0 588.2%	94.4 524.4%
Week 2 no new/nonhealing lesions	47.1 277.1%	22.2 123.3%
Week 4 no flare	88.2 518.8%	83.3 462.8%
Week 4 no new/nonhealing lesions	47.1 277.1%	38.9 216.1%
Week 6 no flare	70.6 415.3%	77.8 432.2%
Week 6 no new/nonhealing lesions	41.2 242.4%	33.3 185%
Week 8 no flare	64.7 380.6%	72.2 401.1%
Week 8 no new/nonhealing lesions	35.3 207.6%	33.3 185%
Week 12 no flare	58.8 345.9%	55.6 308.9%
Week 12 no new/nonhealing lesions	35.3 207.6%	16.7 92.8%
Week 16 no flare	52.9 311.2%	61.1 339.4%
Week 16 no new/nonhealing lesions	23.5 138.2%	16.7 92.8%
Week 20 no flare	47.1 277.1%	50.0 277.8%
Week 20 no new/nonhealing lesions	29.4 172.9%	16.7 92.8%
Week 24 no flare	47.1 277.1%	38.9 216.1%
Week 24 no new/nonhealing lesions	35.3 207.6%	16.7 92.8%
Week 28 no flare	29.4 172.9%	22.2 123.3%
Week 28 no new/nonhealing lesions	17.6 103.5%	11.1 61.7%
Week 32 no flare	35.3 207.6%	27.8 154.4%
Week 32 no new/nonhealing lesions	17.6 103.5%	5.6 31.1%
Week 36 no flare	23.5 138.2%	11.1 61.7%
Week 36 no new/nonhealing lesions	5.9 34.7%	5.6 31.1%
Week 40 no flare	17.6 103.5%	5.6 31.1%
Week 40 no new/nonhealing lesions	11.8 69.4%	0 0%
Week 44 no flare	17.6 103.5%	5.6 31.1%
Week 44 no new/nonhealing lesions	5.9 34.7%	0 0%
Week 48 no flare	17.6 103.5%	0 0%
Week 48 no new/nonhealing lesions	0 0%	0 0%
Week 52 no flare	11.8 69.4%	5.6 31.1%
Week 52 no new/nonhealing lesions	11.8 69.4%	0 0%
Week 56 no flare	11.8 69.4%	0 0%
Week 56 no new/nonhealing lesions	5.9 34.7%	0 0%
Week 60 no flare	88.2 518.8%	83.3 462.8%
Week 60 no new/nonhealing lesions	52.9 311.2%	33.3 185%

9. Secondary Outcome

Title	Plasma Trough Concentrations of Ofatumumab
Description	Only plasma (trough) concentrations of ofatumumab were presented
Time Frame	4 hours post baseline, Days 1-4,7,14, Weeks 4,8,12,16,20,24,36,48,52,56, up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.
Measure Participants	17
4 hours post dose SS	56.60 (NA)
Day 1 Steady State (SS)	1917.50 (NA)
Day 2 Steady State (SS)	2994.20 (NA)
Day 3 Steady State (SS)	3553.80 (NA)
Day 4 Steady State (SS)	3619.20 (NA)
Day 7 Steady State (SS)	3434.90 (NA)
Day 14 Steady State (SS)	2055.30 (NA)
Week 4	311.59 (278.011)
Week 4 SS	1132.70 (NA)
Week 8	1253.60 (439.574)
Week 8 SS	1456.95 (668.994)
Week 12	727.01 (430.834)
Week 12 SS	900.00 (455.930)
Week 16	512.88 (377.189)
Week 16 SS	1043.40 (NA)
Week 20	415.88 (303.307)
Week 20 SS	720.10 (246.356)
Week 24	461.72 (437.717)
Week 24 SS	686.10 (329.699)
Week 36	477.63 (378.112)
Week 36 SS	931.20 (NA)
Week 48	352.95 (300.591)
Week 48 SS	1230.40 (NA)
Week 52 SS	897.30 (NA)
Week 56	436.40 (511.662)
Week 60	76.40 (32.244)
Early withdrawal	925.91 (971.715)

10. Secondary Outcome

Title	Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A
Description	Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Baseline	1 5.9%	0 0%
Week 12	1 5.9%	0 0%
Week 16	0 0%
Week 24	1 5.9%	0 0%
Week 36	1 5.9%	0 0%
Week 48	1 5.9%	0 0%
Week 52	1 5.9%	0 0%
Week 56	1 5.9%	0 0%
Week 60/Early withdrawal	0 0%	0 0%
First 12 weeks of therapy	1 5.9%	0 0%
During on therapy period	1 5.9%	0 0%

11. Secondary Outcome

Title	Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G
Description	Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Baseline	1 5.9%	2 11.1%
Week 12	0 0%	1 5.6%
Week 16	1 5.9%
Week 24	0 0%	1 5.6%
Week 36	0 0%	0 0%
Week 48	0 0%	0 0%
Week 52	0 0%	0 0%
Week 56	0 0%	0 0%
Week 60/Early withdrawal	0 0%	2 11.1%
First 12 weeks of therapy	1 5.9%	3 16.7%
During on therapy period	1 5.9%	4 22.2%

12. Secondary Outcome

Title	Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M
Description	Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Baseline	1 5.9%	1 5.6%
Week 12	4 23.5%	1 5.6%
Week 16	0 0%
Week 24	4 23.5%	0 0%
Week 36	4 23.5%	0 0%
Week 48	3 17.6%	0 0%
Week 52	2 11.8%	0 0%
Week 56	2 11.8%	0 0%
Week 60/Early withdrawal	6 35.3%	2 11.1%
First 12 weeks of therapy	4 23.5%	1 5.6%
During on therapy period	6 35.3%	2 11.1%

13. Secondary Outcome

Title	Largest Mean Decrease From Baseline for Immunoglobulin A, G and M
Description	Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Immunoglobulin A	-0.185 (0.1181)	-0.472 (0.7116)
Immunoglobulin G	-1.172 (0.9390)	-0.955 (0.6205)
Immunoglobulin M	-0.231 (0.1152)	-0.263 (0.3053)

14. Secondary Outcome

Title	Change From Baseline for CD19+ B Cell Count
Description	CD19+ B cell count will be performed using Flow Cytometry
Time Frame	Baseline up to approximately 60 weeks

Outcome Measure Data

Analysis Population Description

number of participants varied across visits

Arm/Group Title	Ofatumumab	Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.	Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Measure Participants	17	18
Week 12	-0.24940 (0.228704)	0.03080 (0.072358)
Week 16	0.08000 (NA)
Week 24	-0.28607 (0.265327)	-0.04022 (0.197867)
Week 36	-0.20525 (0.052703)	-0.10033 (0.021385)
Week 48	-0.19717 (0.061436)	-0.00200 (NA)
Week 52	-0.16300 (0.023335)	0.09600 (NA)
Week 56	-0.16300 (0.023335)	0.01000 (NA)
Week 60/Early withdrawal	-0.21403 (0.190282)	0.00367 (0.190375)

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 60 months
Arm/Group Title	Ofatumumab SC		Placebo
Arm/Group Description	Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.		Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
All Cause Mortality
	Ofatumumab SC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/18 (0%)
Serious Adverse Events
	Ofatumumab SC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		1/18 (5.6%)
Investigations
Hepatic enzyme increased	1/17 (5.9%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/17 (0%)		1/18 (5.6%)
Other (Not Including Serious) Adverse Events
	Ofatumumab SC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/17 (82.4%)		8/18 (44.4%)
Blood and lymphatic system disorders
Anaemia	1/17 (5.9%)		0/18 (0%)
Ear and labyrinth disorders
Ear pain	1/17 (5.9%)		0/18 (0%)
Eye disorders
Conjunctival discolouration	1/17 (5.9%)		0/18 (0%)
Eye irritation	1/17 (5.9%)		0/18 (0%)
Eye swelling	1/17 (5.9%)		0/18 (0%)
Ocular hyperaemia	1/17 (5.9%)		1/18 (5.6%)
Vision blurred	0/17 (0%)		1/18 (5.6%)
Gastrointestinal disorders
Abdominal distension	1/17 (5.9%)		0/18 (0%)
Abdominal pain	1/17 (5.9%)		0/18 (0%)
Diarrhoea	1/17 (5.9%)		0/18 (0%)
Gastrooesophageal reflux disease	1/17 (5.9%)		0/18 (0%)
Nausea	3/17 (17.6%)		1/18 (5.6%)
Tongue ulceration	0/17 (0%)		1/18 (5.6%)
General disorders
Chills	3/17 (17.6%)		0/18 (0%)
Fatigue	2/17 (11.8%)		1/18 (5.6%)
Influenza like illness	1/17 (5.9%)		1/18 (5.6%)
Local reaction	0/17 (0%)		1/18 (5.6%)
Malaise	1/17 (5.9%)		0/18 (0%)
Pain	0/17 (0%)		2/18 (11.1%)
Pyrexia	3/17 (17.6%)		0/18 (0%)
Infections and infestations
Bronchitis	0/17 (0%)		1/18 (5.6%)
Cellulitis	0/17 (0%)		2/18 (11.1%)
Folliculitis	1/17 (5.9%)		0/18 (0%)
Gastroenteritis	0/17 (0%)		1/18 (5.6%)
Gastroenteritis viral	0/17 (0%)		1/18 (5.6%)
Herpes simplex	0/17 (0%)		1/18 (5.6%)
Influenza	1/17 (5.9%)		0/18 (0%)
Nasopharyngitis	0/17 (0%)		1/18 (5.6%)
Oral candidiasis	0/17 (0%)		1/18 (5.6%)
Tooth abscess	1/17 (5.9%)		0/18 (0%)
Upper respiratory tract infection	2/17 (11.8%)		1/18 (5.6%)
Injury, poisoning and procedural complications
Arthropod sting	1/17 (5.9%)		0/18 (0%)
Post procedural complication	1/17 (5.9%)		0/18 (0%)
Procedural nausea	1/17 (5.9%)		0/18 (0%)
Procedural pain	1/17 (5.9%)		0/18 (0%)
Investigations
B-lymphocyte count decreased	1/17 (5.9%)		0/18 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/17 (0%)		1/18 (5.6%)
Hypoglycaemia	1/17 (5.9%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/17 (11.8%)		1/18 (5.6%)
Metatarsalgia	1/17 (5.9%)		0/18 (0%)
Muscular weakness	0/17 (0%)		1/18 (5.6%)
Musculoskeletal discomfort	1/17 (5.9%)		0/18 (0%)
Myalgia	1/17 (5.9%)		0/18 (0%)
Plantar fasciitis	0/17 (0%)		1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/17 (0%)		1/18 (5.6%)
Nervous system disorders
Dizziness	1/17 (5.9%)		1/18 (5.6%)
Headache	2/17 (11.8%)		0/18 (0%)
Syncope	1/17 (5.9%)		0/18 (0%)
Tremor	1/17 (5.9%)		1/18 (5.6%)
Psychiatric disorders
Anxiety	1/17 (5.9%)		1/18 (5.6%)
Persistent depressive disorder	1/17 (5.9%)		0/18 (0%)
Renal and urinary disorders
Calculus urinary	1/17 (5.9%)		0/18 (0%)
Nephrolithiasis	1/17 (5.9%)		0/18 (0%)
Nocturia	1/17 (5.9%)		0/18 (0%)
Reproductive system and breast disorders
Semen discolouration	1/17 (5.9%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/17 (11.8%)		0/18 (0%)
Epistaxis	0/17 (0%)		1/18 (5.6%)
Sinus congestion	1/17 (5.9%)		0/18 (0%)
Upper respiratory tract congestion	0/17 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/17 (5.9%)		0/18 (0%)
Dermatitis allergic	0/17 (0%)		1/18 (5.6%)
Eczema	1/17 (5.9%)		1/18 (5.6%)
Rash	1/17 (5.9%)		2/18 (11.1%)
Vascular disorders
Hot flush	1/17 (5.9%)		0/18 (0%)
Hypertension	2/17 (11.8%)		1/18 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.