IVIg Efficacy Study to Treat Cutaneous Lupus Erythematosus
Study Details
Study Description
Brief Summary
The purpose of this research study is to show that non-steroidal treatment with intravenous immunoglobulin (IVIg) can replace current systemic immunosuppressive therapy in cutaneous lupus erythematosis (CLE) patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Early Phase 1 |
Detailed Description
The ultimate goal of this pilot project is to generate proof-of-concept data showing that treatment with intravenous immunoglobulin (IVIg) can replace current systemic immunosuppressive therapy in cutaneous lupus erythematosis (CLE) patients. This project has relevant clinical implications due to the severe side effects of and lack of response to current therapies.
From the review of literature, it can be postulated that:
-
the beneficial effects of IVIg for patients with CLE should be prompt, with marked improvement within a few weeks;
-
clinical improvement should last several weeks after the last infusion; and
-
remission may be prolonged by maintenance IVIg therapy.
Although this is only a non-controlled study, the investigator expects that IVIg will improve CLE, including those resistant to standard treatments. It is anticipated that treatment with IVIg will facilitate healing of extensive cutaneous lesions and achieve rapid remission. Maintenance therapy with repeated monthly pulses of IVIg is expected to keep the disease in remission during the treatment-free follow up observational period. The results will provide the basis a multicenter randomized controlled study to identify which CLE subsets will benefit the most and which protocol will provide the optimal clinical outcome.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: IVIg as a monotherapy IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. |
Drug: IVIg
All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cutaneous Lupus Erythematosus Disease Area and Severity Index - Total Activity Score (CLASI - TAS) [Initial, 1st Visit - 9th Visit]
Disease activity will be measured using the CLASI activity score that describes the activity of the disease. This score ranges from 0-70, with higher scores indicating more severe skin disease. This clinical assessment tool enables standardized assessments of response to therapy. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis.
- Skindex 29 [Initial, 1st Visit - 9th Visit]
The subjects also evaluated their skin-specific quality of life with the Skindex-29 - the questionnaire consisting of 29 items used to calculate three subscales: symptoms (pain, itch, burning, sensitivity), emotions (depression, anxiety, embarrassment, anger) and functioning (sleep, relationships with others). All assessments were repeated at all study visits. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis.
Secondary Outcome Measures
- Mean Percent Change in Physician's Subjective Assessment of Improvement (PSAI) [Initial, 1st Visit - 9th Visit]
At clinic visits, the investigator will categorize the change in disease activity in each patient as improved, unchanged, or worse since the last visit. Estimated change in disease activity will be based on the investigator's subjective assessment of the patient's skin disease. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis.
- Mean Percent Change in Physician's Subjective Assessment of Severity (PSAS) [Initial, 1st Visit - 9th Visit]
At clinic visits, the investigator will categorize the change in disease activity in each patient as improved, unchanged, or worse since the last visit. Estimated change in disease activity will be based on the investigator's subjective assessment of the patient's skin disease. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis.
- Cutaneous Lupus Erythematosus Disease Area and Severity Index - Total Damage Score (CLASI - TDS) [Initial, 1st Visit - 9th Visit]
Disease activity will be measured using the CLASI activity score that describes the damage of the disease. This score ranges from 0-70, with higher scores indicating more severe skin disease. This clinical assessment tool enables standardized assessments of response to therapy. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. All patients were measured identically in all visits.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
-
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
-
Be at least 18 years of age at time of informed consent.
-
Have had a diagnosis of CLE
-
Currently has active CLE (any subtype) established by standard clinical and histo- and immunopathologic criteria
-
Falls into one of the two following cohorts:
-
Cohort 1 - Has received a standard systemic therapy without a therapeutic response for a minimum of one month
-
Cohort 2 - Has not received any systemic treatment
Exclusion Criteria:
-
Subject is not over 18 years of age.
-
Subject cannot understand or follow directions.
-
Subject is a female of child-bearing potential and unwilling to use a form of highly effective birth control.
-
Subject is pregnant, planning to get pregnant, or breast feeding.
-
Subject has a known history of immunoglobulin A (IgA) deficiency.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Institute for Clinical and Translational Science (ICTS) | Irvine | California | United States | 92697 |
| 2 | Unversity of California, Irvine Healthcare, Dermatology, Gottschalk Medical Plaza | Irvine | California | United States | 92697 |
Sponsors and Collaborators
- University of California, Irvine
- Grifols Therapeutics LLC
Investigators
- Principal Investigator: Sergei Grando, MD PhD D.Sc., University of California, Irvine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2013-9351
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Period Title: Overall Study | |
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Overall Participants | 16 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
15
93.8%
|
| >=65 years |
1
6.3%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
15
93.8%
|
| Male |
1
6.3%
|
Outcome Measures
| Title | Mean Percent Change in Physician's Subjective Assessment of Improvement (PSAI) |
|---|---|
| Description | At clinic visits, the investigator will categorize the change in disease activity in each patient as improved, unchanged, or worse since the last visit. Estimated change in disease activity will be based on the investigator's subjective assessment of the patient's skin disease. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. |
| Time Frame | Initial, 1st Visit - 9th Visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Measure Participants | 16 |
| Intial |
100
(0)
|
| 1st Visit |
100
(0)
|
| 2nd Visit |
100
(0)
|
| 3rd Visit |
136
(79)
|
| 4th Visit |
104
(48)
|
| 5th Visit |
105
(52)
|
| 6th Visit |
117
(37)
|
| 7th Visit |
133
(47)
|
| 8th Visit |
150
(77)
|
| 9th Visit |
100
(29)
|
| Title | Mean Percent Change in Physician's Subjective Assessment of Severity (PSAS) |
|---|---|
| Description | At clinic visits, the investigator will categorize the change in disease activity in each patient as improved, unchanged, or worse since the last visit. Estimated change in disease activity will be based on the investigator's subjective assessment of the patient's skin disease. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. |
| Time Frame | Initial, 1st Visit - 9th Visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Measure Participants | 16 |
| Initial |
100
(0)
|
| 1st Visit |
100
(0)
|
| 2nd Visit |
98
(8)
|
| 3rd Visit |
100
(10)
|
| 4th Visit |
97
(18)
|
| 5th Visit |
92
(19)
|
| 6th Visit |
92
(18)
|
| 7th Visit |
92
(20)
|
| 8th Visit |
90
(18)
|
| 9th Visit |
90
(17)
|
| Title | Cutaneous Lupus Erythematosus Disease Area and Severity Index - Total Activity Score (CLASI - TAS) |
|---|---|
| Description | Disease activity will be measured using the CLASI activity score that describes the activity of the disease. This score ranges from 0-70, with higher scores indicating more severe skin disease. This clinical assessment tool enables standardized assessments of response to therapy. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. |
| Time Frame | Initial, 1st Visit - 9th Visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Measure Participants | 16 |
| Initial |
100
(0)
|
| 1st Visit |
94
(30)
|
| 2nd Visit |
84
(29)
|
| 3rd Visit |
94
(52)
|
| 4th Visit |
86
(19)
|
| 5th Visit |
85
(14)
|
| 6th Visit |
72
(37)
|
| 7th Visit |
68
(33)
|
| 8th Visit |
81
(17)
|
| 9th Visit |
71
(13)
|
| Title | Cutaneous Lupus Erythematosus Disease Area and Severity Index - Total Damage Score (CLASI - TDS) |
|---|---|
| Description | Disease activity will be measured using the CLASI activity score that describes the damage of the disease. This score ranges from 0-70, with higher scores indicating more severe skin disease. This clinical assessment tool enables standardized assessments of response to therapy. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. All patients were measured identically in all visits. |
| Time Frame | Initial, 1st Visit - 9th Visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Measure Participants | 16 |
| Initial |
100
(0)
|
| 1st Visit |
100
(0)
|
| 2nd Visit |
100
(0)
|
| 3rd Visit |
100
(0)
|
| 4th Visit |
100
(0)
|
| 5th Visit |
100
(0)
|
| 6th Visit |
100
(0)
|
| 7th Visit |
100
(0)
|
| 8th Visit |
100
(0)
|
| 9th Visit |
100
(0)
|
| Title | Skindex 29 |
|---|---|
| Description | The subjects also evaluated their skin-specific quality of life with the Skindex-29 - the questionnaire consisting of 29 items used to calculate three subscales: symptoms (pain, itch, burning, sensitivity), emotions (depression, anxiety, embarrassment, anger) and functioning (sleep, relationships with others). All assessments were repeated at all study visits. Results expressed relative to the mean initial value of all patients, taken as 100%. Each proceeding visit will be relative to the initial visit. A decrease in percentage represents improvement while an increase in percentage indicates worsening of CLE. Visits occur on a month-to-month basis. |
| Time Frame | Initial, 1st Visit - 9th Visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVIg as a Monotherapy |
|---|---|
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. |
| Measure Participants | 16 |
| Initial |
100
(0)
|
| 1st Visit |
97
(3)
|
| 2nd Visit |
94
(9)
|
| 3rd Visit |
92
(12)
|
| 4th Visit |
90
(15)
|
| 5th Visit |
81
(21)
|
| 6th Visit |
79
(23)
|
| 7th Visit |
83
(30)
|
| 8th Visit |
99
(11)
|
| 9th Visit |
82
(21)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | IVIg as a Monotherapy | |
| Arm/Group Description | IVIg will be used as a first line treatment. Topical treatment will be stopped at the beginning of IVIg therapy. IVIg: All enrolled subjects will receive IVIg treatment following the protocol that proved to be efficacious in the treatment of patients with autoimmune blistering diseases as well as some patients with CLE. The drug will be administered at 500 mg/kg/day on consecutive days up to a total of 2 g/kg/month for 3 months in the Institute for Clinical and Translational Science (ICTS) at University of California, Irvine. After 3 months of treatment, IVIg will be discontinued and the subjects will be monitored for additional 6 months for a possible relapse. In the case of relapse, which is expected to occur in <25% subjects, the subjects will be re-treated by the standard protocol. | |
All Cause Mortality |
||
| IVIg as a Monotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| IVIg as a Monotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| IVIg as a Monotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/16 (56.3%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 2/16 (12.5%) | |
| Neutropenia | 1/16 (6.3%) | |
| Gastrointestinal disorders | ||
| GI Upset | 1/16 (6.3%) | |
| Nausea/Vomting | 2/16 (12.5%) | |
| General disorders | ||
| Fever | 2/16 (12.5%) | |
| Immune system disorders | ||
| Oral Lupus Flare | 1/16 (6.3%) | |
| Lupus Flare | 2/16 (12.5%) | |
| Infections and infestations | ||
| Diabetic Foot Ulcer | 1/16 (6.3%) | |
| Musculoskeletal and connective tissue disorders | ||
| Back Spasms | 1/16 (6.3%) | |
| Nervous system disorders | ||
| Headache | 3/16 (18.8%) | 5 |
| Skin and subcutaneous tissue disorders | ||
| Herpes - Associated Erythema Multiforme | 1/16 (6.3%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Sergei A. Grando |
|---|---|
| Organization | UC Irvine Dermatology Research Center |
| Phone | 949 824 7103 |
| sgrando@uci.edu |
- 2013-9351