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NCT01920477

Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

Terminated Phase 3 Results posted Last updated 6 June 2019
What this trial tests

Phase 3 trial testing Ofatumumab in Pemphigus Vulgaris in 35 participants. Terminated before completion.

Timeline
13 August 2013
Primary endpoint
13 April 2016
11 January 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment35
Start date13 August 2013
Primary completion13 April 2016
Estimated completion11 January 2018
Sites16 locations across Italy, Japan, Greece, Israel, Poland, Romania, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 70, any sex, with Pemphigus Vulgaris. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy Primary · 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.

GroupValue95% CI
Ofatumumab0
Placebo0
Duration of Remission on Minimal Steroid Therapy Primary · 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.

GroupValue95% CI
Ofatumumab168.0± 73.33
Placebo122.0± NA
Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 Secondary · 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.

GroupValue95% CI
Ofatumumab17.6
Placebo5.6
Time to Remission While on Minimal Steroid Therapy by Week 60. Secondary · 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

GroupValue95% CI
OfatumumabNA57.0 – NA
PlaceboNANA – NA
Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. Secondary · 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.

GroupValue95% CI
Ofatumumab168± 73.33
Placebo122.0± NA
Time to Initial Flare/Relapse by Week 60 Secondary · 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

GroupValue95% CI
Ofatumumab448NA – NA
Placebo169.086.0 – 284.0
Percentage of Participants With no Flare/Relapse by Week 60 Secondary · 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

Week 2 no flare
GroupValue95% CI
Ofatumumab100.0
Placebo94.4
Week 2 no new/nonhealing lesions
GroupValue95% CI
Ofatumumab47.1
Placebo22.2
Week 4 no flare
GroupValue95% CI
Ofatumumab88.2
Placebo83.3
Week 4 no new/nonhealing lesions
GroupValue95% CI
Ofatumumab47.1
Placebo38.9
Week 6 no flare
GroupValue95% CI
Ofatumumab70.6
Placebo77.8
Week 6 no new/nonhealing lesions
GroupValue95% CI
Ofatumumab41.2
Placebo33.3
Week 8 no flare
GroupValue95% CI
Ofatumumab64.7
Placebo72.2
Week 8 no new/nonhealing lesions
GroupValue95% CI
Ofatumumab35.3
Placebo33.3
Plasma Trough Concentrations of Ofatumumab Secondary · 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

4 hours post dose SS
GroupValue95% CI
Ofatumumab56.60± NA
Day 1 Steady State (SS)
GroupValue95% CI
Ofatumumab1917.50± NA
Day 2 Steady State (SS)
GroupValue95% CI
Ofatumumab2994.20± NA
Day 3 Steady State (SS)
GroupValue95% CI
Ofatumumab3553.80± NA
Day 4 Steady State (SS)
GroupValue95% CI
Ofatumumab3619.20± NA
Day 7 Steady State (SS)
GroupValue95% CI
Ofatumumab3434.90± NA
Day 14 Steady State (SS)
GroupValue95% CI
Ofatumumab2055.30± NA
Week 4
GroupValue95% CI
Ofatumumab311.59± 278.011
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A Secondary · Baseline up to approximately 60 weeks

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

Baseline
GroupValue95% CI
Ofatumumab1
Placebo0
Week 12
GroupValue95% CI
Ofatumumab1
Placebo0
Week 16
GroupValue95% CI
Placebo0
Week 24
GroupValue95% CI
Ofatumumab1
Placebo0
Week 36
GroupValue95% CI
Ofatumumab1
Placebo0
Week 48
GroupValue95% CI
Ofatumumab1
Placebo0
Week 52
GroupValue95% CI
Ofatumumab1
Placebo0
Week 56
GroupValue95% CI
Ofatumumab1
Placebo0
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G Secondary · Baseline up to approximately 60 weeks

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

Baseline
GroupValue95% CI
Ofatumumab1
Placebo2
Week 12
GroupValue95% CI
Ofatumumab0
Placebo1
Week 16
GroupValue95% CI
Placebo1
Week 24
GroupValue95% CI
Ofatumumab0
Placebo1
Week 36
GroupValue95% CI
Ofatumumab0
Placebo0
Week 48
GroupValue95% CI
Ofatumumab0
Placebo0
Week 52
GroupValue95% CI
Ofatumumab0
Placebo0
Week 56
GroupValue95% CI
Ofatumumab0
Placebo0
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M Secondary · Baseline up to approximately 60 weeks

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

Baseline
GroupValue95% CI
Ofatumumab1
Placebo1
Week 12
GroupValue95% CI
Ofatumumab4
Placebo1
Week 16
GroupValue95% CI
Placebo0
Week 24
GroupValue95% CI
Ofatumumab4
Placebo0
Week 36
GroupValue95% CI
Ofatumumab4
Placebo0
Week 48
GroupValue95% CI
Ofatumumab3
Placebo0
Week 52
GroupValue95% CI
Ofatumumab2
Placebo0
Week 56
GroupValue95% CI
Ofatumumab2
Placebo0
Largest Mean Decrease From Baseline for Immunoglobulin A, G and M Secondary · 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

Immunoglobulin A
GroupValue95% CI
Ofatumumab-0.185± 0.1181
Placebo-0.472± 0.7116
Immunoglobulin G
GroupValue95% CI
Ofatumumab-1.172± 0.9390
Placebo-0.955± 0.6205
Immunoglobulin M
GroupValue95% CI
Ofatumumab-0.231± 0.1152
Placebo-0.263± 0.3053

Adverse events — posted to ClinicalTrials.gov

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. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ofatumumab SC
Serious: 1/17 (6%)
Deaths: 0/17
Placebo
Serious: 1/18 (6%)
Deaths: 0/18

Serious adverse events (2 terms)

ReactionSystemOfatumumab SCPlacebo
Hepatic enzyme increasedInvestigations
AngioedemaSkin and subcutaneous tissue disorders
Other adverse events (65 terms — click to expand)

ReactionSystemOfatumumab SCPlacebo
NauseaGastrointestinal disorders
ChillsGeneral disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
PainGeneral disorders
CellulitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Ear painEar and labyrinth disorders
Conjunctival discolourationEye disorders
Eye irritationEye disorders
Eye swellingEye disorders
Ocular hyperaemiaEye disorders
Vision blurredEye disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Tongue ulcerationGastrointestinal disorders
Influenza like illnessGeneral disorders
Local reactionGeneral disorders
MalaiseGeneral disorders
BronchitisInfections and infestations
FolliculitisInfections and infestations
GastroenteritisInfections and infestations
Gastroenteritis viralInfections and infestations
Herpes simplexInfections and infestations
InfluenzaInfections and infestations
NasopharyngitisInfections and infestations
Oral candidiasisInfections and infestations
Tooth abscessInfections and infestations
Arthropod stingInjury, poisoning and procedural complications
Post procedural complicationInjury, poisoning and procedural complications
Procedural nauseaInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications

Most-reported serious reactions: Hepatic enzyme increased, Angioedema.

Data from ClinicalTrials.gov NCT01920477 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. B cell depletion therapies in autoimmune disease: advances and mechanistic insights.
    Lee DSW, Rojas OL, Gommerman JL. · · 2021 · cited 496× · PMID 33324003 · DOI 10.1038/s41573-020-00092-2
  2. Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment.
    Du FH, Mills EA, Mao-Draayer Y. · · 2017 · cited 120× · PMID 29143151 · DOI 10.1007/s13317-017-0100-y
  3. B Cell Modulation Strategies in Autoimmune Diseases: New Concepts.
    Musette P, Bouaziz JD. · · 2018 · cited 86× · PMID 29706952 · DOI 10.3389/fimmu.2018.00622
  4. Current Clinical Trials in Pemphigus and Pemphigoid.
    Izumi K, Bieber K, Ludwig RJ. · · 2019 · cited 51× · PMID 31130959 · DOI 10.3389/fimmu.2019.00978
  5. Treatment considerations for patients with pemphigus during the COVID-19 pandemic.
    Shakshouk H, Daneshpazhooh M, Murrell DF, Lehman JS. · · 2020 · cited 47× · PMID 32283243 · DOI 10.1016/j.jaad.2020.04.005
  6. Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases-Implications for Therapeutic Approaches.
    Fetter T, Niebel D, Braegelmann C, Wenzel J. · · 2020 · cited 43× · PMID 33297481 · DOI 10.3390/cells9122627
  7. The pathogenesis of bullous skin diseases.
    Yang M, Wu H, Zhao M, Chang C, et al · · 2019 · cited 26× · PMID 32743502 · DOI 10.1016/j.jtauto.2019.100014
  8. Targeting therapy in pemphigus: Where are we now and where are we going?
    Abulikemu K, Hu F, Liang J, Kang X. · · 2023 · cited 15× · PMID 37292301 · DOI 10.1016/j.heliyon.2023.e16679

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