Immunoadsorption, Dexamethasone Pulse Therapy and Rituximab for Pemphigus

• Sponsor: University of Luebeck (Other)
• Overall Status: Completed
• CT.gov ID: NCT00656656
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arm: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Pemphigus is a severe autoimmune blistering disease mediated by circulating antibodies against certain proteins important for maintaining skin integrity. Protein A immunoadsorption is a dialysis-like technique selectively removing the antibodies from patient's blood. Rituximab is a synthetic antibody capable of destroying B cells. B cells are responsible for production of antibodies in the patients blood that, in turn, lead to clinical signs of pemphigus. Dexamethasone pulse therapy is a high-dose short-term corticosteroid therapy that may be used to suppress autoantibody production in pemphigus. While each of these three therapies had been used to treat pemphigus, none was shown effective in all cases. The hypothesis of this study is that a combination of protein A immunoadsorption, rituximab and dexamethasone is more effective that either of these treatments alone in achieving a rapid and durable improvement or cure in patients with pemphigus.

Condition or Disease	Intervention/Treatment	Phase
Pemphigus	Drug: Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combined Treatment of Autoimmune Bullous Diseases With Protein A Immunoadsorption, Dexamethasone Pulse Therapy and Rituximab
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: Immunoadsorption/Dexamethasone/Rituximab	Drug: Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine; Protein A Immunoadsorption: performed on 3 consecutive days every 3 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o.

Outcome Measures

Primary Outcome Measures

1. Number of Patients Achieving a Short- and Long-term Remission of Pemphigus [up to 43 months]

   Clinical remission was graded as partial remission on therapy, complete remission on therapy and complete remission off therapy, as described by Murell et al, J Am Acad Dermatol, 2008; 58:1043-6.

Secondary Outcome Measures

1. Number of Patients Who Experienced Side-effects of Treatment [up to 43 months]

   Patients who experienced side-effects were counted. In addition, the nature and severity of side-effects were recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of pemphigus confirmed by immunofluorescence and desmoglein ELISA.

• Severe disease or past treatment(s) not effective or past treatment(s) not tolerated.

Exclusion Criteria:

• General condition too poor to tolerate immunoadsorption treatment.

• Severe dementia or psychiatric disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Dermatology, University of Luebeck	Luebeck	Schleswig-Holstein	Germany	23552

Sponsors and Collaborators

• University of Luebeck

Investigators

• Principal Investigator: Detlef Zillikens, MD, Department of Dermatology, University of Luebeck

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Kasperkiewicz, Dermatologist, University of Luebeck
• ClinicalTrials.gov Identifier: NCT00656656
• Other Study ID Numbers: Pemphigus-Luebeck
• First Posted: Apr 11, 2008
• Last Update Posted: Mar 13, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Michael Kasperkiewicz, Dermatologist, University of Luebeck: pemphigus; rituximab; immunoadsorption; dexamethasone; treatment; management
• Additional relevant MeSH terms: Pemphigus; Dexamethasone; Rituximab; Azathioprine

Study Results

Participant Flow

Arm/Group Title	Immunoadsorption/Dexamethasone/Rituximab
Arm/Group Description	Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine/Mycophenolate mofetil Protein A Immunoadsorption: performed on 3 consecutive days every 3-4 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days initially every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o. Mycophenolate mofetil 2 g/d p.o.
Period Title: Overall Study
STARTED	23
COMPLETED	23
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Immunoadsorption/Dexamethasone/Rituximab
Arm/Group Description	Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine/Mycophenolate mofetil Protein A Immunoadsorption: performed on 3 consecutive days every 3-4 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days initially every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o. Mycophenolate mofetil 2 g/d p.o.
Overall Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 73.9%
>=65 years	6 26.1%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	11 47.8%
Male	12 52.2%
Region of Enrollment (participants) [Number]
Germany	23 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Achieving a Short- and Long-term Remission of Pemphigus
Description	Clinical remission was graded as partial remission on therapy, complete remission on therapy and complete remission off therapy, as described by Murell et al, J Am Acad Dermatol, 2008; 58:1043-6.
Time Frame	up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoadsorption/Dexamethasone/Rituximab
Arm/Group Description	Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine/Mycophenolate mofetil Protein A Immunoadsorption: performed on 3 consecutive days every 3-4 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days initially every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o. Mycophenolate mofetil 2 g/d p.o.
Measure Participants	23
Count of Participants [Participants]	23 100%

2. Secondary Outcome

Title	Number of Patients Who Experienced Side-effects of Treatment
Description	Patients who experienced side-effects were counted. In addition, the nature and severity of side-effects were recorded.
Time Frame	up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoadsorption/Dexamethasone/Rituximab
Arm/Group Description	Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine/Mycophenolate mofetil Protein A Immunoadsorption: performed on 3 consecutive days every 3-4 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days initially every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o. Mycophenolate mofetil 2 g/d p.o.
Measure Participants	23
Count of Participants [Participants]	2 8.7%

Adverse Events

Arm/Group Title	Immunoadsorption/Dexamethasone/Rituximab
Arm/Group Description	Combination of Protein A Immunoadsorption, Rituximab, Dexamethasone plus Azathioprine/Mycophenolate mofetil Protein A Immunoadsorption: performed on 3 consecutive days every 3-4 weeks Rituximab: 1000 mg i.v. given twice at a 2-week interval Dexamethasone pulse therapy: 100 mg i.v. given on 3 consecutive days initially every 3 weeks Azathioprine: 2.5 mg/kg body weight daily p.o. Mycophenolate mofetil 2 g/d p.o.
All Cause Mortality
	Immunoadsorption/Dexamethasone/Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Immunoadsorption/Dexamethasone/Rituximab
	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)
Infections and infestations
Sepsis	1/23 (4.3%)
extensive herpes simplex	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Immunoadsorption/Dexamethasone/Rituximab
	Affected / at Risk (%)	# Events
Total	0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.