immunoglobulin infusion as adjuvant therapy in patients with Pemphigus Vulgaris

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2013-000211-24-DE
• Date of registration: 08/07/2013
• Prospective Registration: Yes
• Primary sponsor: Ruprecht-Karls-University Heidelberg
• Public title: immunoglobulin infusion as adjuvant therapy in patients with Pemphigus Vulgaris
• Scientific title: A multicenter, randomized, placebo-controlled, double-blind proof of concept study to evaluate the efficacy and safety of the human normal immunoglobulin Intratect® 5% for intravenous use as adjuvant therapy in patients with Pemphigus Vulgaris - IMAT-PV
• Date of first enrolment: 01/10/2013
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000211-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Department of Dermatology
• Affiliation: University of Heidelberg

• Name: Department of Dermatology
• Affiliation: University of Heidelberg

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with clinical signs of Pemphigus vulgaris
2. Patients with Pemphigus vulgaris proven by direct immunofluorescence (deposition of IgG intraepidermally on the keratinocyte membrane)
3. Patients with relapse of Pemphigus vulgaris < 2 months before inclusion. (Relapse is defined by the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions in a person who has achieved disease control).
4. Prednisone doses (or the equivalent) = 10 mg per day
5. Indication for or therapy with additional immunosuppressive therapy (e.g. Azathioprine or Mycophenolatemofetil)
6. Age = 18years
7. Written informed consent, signed and dated
8. Sufficient knowledge of languages (German)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Patients with drug-induced forms of Pemphigus Vulgaris are excluded
2. Patients relapsing at a dose under 10 mg Prednisone (or the equivalent) per day
3. Clinically significant heart disease (NYHA Class III or IV)
4. Clinically significant renal insufficiency (CDC III or IV)
5. Patients with a history of thromboembolic episodes such as deep vein thromboses, myocardial infarction or stroke
6. HIV, HCV or HBV infections
7. Bleeding disorders
8. Patients with serious intercurrent illness, requiring hospitalization
9. Patients taking or requiring immunosuppressive drugs such as systemic corticosteroids other than study medication for a distinct medical disorder (e.g. rheumatoid arthritis). Topical or inhalational steroids are permitted
10. Patients treated with steroid pulse therapy, plasma exchange therapy within 30 days, other biotherapeutics (e.g. TNF-a inhibitors, interferons, rituximab) or HD-IVIg within 60 days before the start of study treatment.
11. Active malignancy within 1 year prior to entry into the study, except for cured non-melanoma skin cancer and cervical carcinoma in situ.
12. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
13. Participation in chemotherapy or irradiation therapy within 4 weeks prior to enrolment.
14. Participation in any other clinical trial within 4 weeks prior to enrolment and treatment with another investigational agent within 5 elimination half-lives prior to enrolment.
15. Pregnancy or breastfeeding woman, or women of childbearing potential refusing or unable to use effective means of contraception (i.e. oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, female sterilisation or condoms).
16. History of severe allergic reactions to study drugs, vaccines or unknown allergens
17. Patients with known absolute IgA deficiency
18. Patients who are unable to be treated due to obesity
19. Patients who are unable to receive concomitant immunosuppressive therapy
20. Suspicion of drug and / or alcohol abuse
The patient planned to be enrolled is an employee of any involved investigator or any involved institution including the sponsor of the trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

patients with Pemphigus vulgaris
MedDRA version: 16.0 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: Intratect 5%
Product Name: Intratect
Pharmaceutical Form: Infusion
Other descriptive name: WATER FOR INJECTION
Concentration unit: ml millilitre(s)
Concentration type: up to
Concentration number: 1-
Other descriptive name: GLYCINE
Concentration unit: µmol micromole(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Efficacy parameters
a. Time to achieve control of disease activity (beginning of consolidation phase)
b. The proportion of patients in remission on therapy (2 months no new lesions), (minimal therapy = 10mg/d prednisolone ± minimal adjuvant therapy = 2 months)
c. The proportion of patients with premature discontinuation of the study due to relapse
d. Change in ‘Pemphigus Disease Area Index’ (PDAI), Baseline to month 12
e. Change in ‘Autoimmune Bullous Skin Disorder Intensity Score’ (ABSIS), Baseline to month 12
f. Change in ‘Dermatology Life Quality Index’ (DLQI)
g. Cumulative doses of steroid and azathioprine or mycophenolate mofetil
h. Reduction of serum anti-Dsg1 and Dsg3 antibody titers
Safety
a. Number of adverse events including safety laboratory parameters and immunological parameters

Main Objective: The proportion of patients suffering relapse (Relapse rate) during IVIG or placebo treatment within 12 months
Relapse: The appearance of = 3 new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions in a patient who has achieved disease control.

Primary end point(s): The primary objective of this study is the clinical efficacy as measured by the proportion of patients suffering relapse during IVIG or placebo treatment within 12 months (relapse rate on therapy).

Timepoint(s) of evaluation of this end point: Relapses will be analysed individually within first 12 months after start of treatment (relapse on therapy).

Secondary Outcome(s)

Secondary end point(s): The time to achieve control of disease activity, the time to the beginning of the consolidation phase and the time to the end of the consolidation phase will be listed in a single list by treatment group and patient. Each single patient’s remission will be listed with time along with start and end time of therapy. The PDAI, DLQI and ABSIS will be plotted over time as connected plots for all patients of each group, as one diagram for each group. The corticosteroid/azathioprine/mycophenolate daily dose will be plotted as over time as connected plots for all patients of each group, as one diagram for each group. The cumulative dose of corticosteroid/azathioprine/mycophenolate will be listed by treatment group and patient. Levels of IgG autoantibodies will be plotted over time as connected plots for all patients of each group, as one diagram for each group. All analyses will be performed on the full analysis set.

Timepoint(s) of evaluation of this end point: see above (Point 5.2)

Secondary ID(s)

IMAT-PV

Source(s) of Monetary Support

Biotest AG

Ethics review

Status: Approved
Approval date: 01/10/2013
Contact: