Primary Objective: To evaluate the achievement of partial remission by apremilast combined with doxycyclineat week sixteen (t=16). Secondary Objectives: • Complete remission at week sixteen; • Disease control at week six (t=6); • Drug survival;•…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Partial remission will be analysed in week sixteen (t=16). Partial remission is
defined as presence of transient new lesions that heal within one week OR >=30%
decrease of VAS. At week six (t= 6), patients that showed no disease control on
apremilast combined with doxycycline will be excluded from the pilot study.
Disease control is defined as *the time that new lesions cease to form and
established lesions begin to heal OR pruritic symptoms start to abate (minimal
1-point decrease of VAS)*.
Secondary outcome
• Achievement of complete remission at week sixteen. Complete remission is
defined as absence of new or established lesions or pruritus.30
• Proportion of patient with drug survival at t=16.
• Proportion of patients with disease control at t=6.
• Mean decrease in periphery blood eosinophil count.
• Mean decrease in BP180 Nc16a titers by ELISA.
• Change in genexpression by RNA sequencing measured at t=0 and t=16.
The following outcomes will be used for measuring clinical efficacy:
• mean reduction in Visual Analogue Scale (VAS)
• mean decrease in Dermatology Quality of Life index (DLQI), autoimmune
blistering disease quality of life (AIBDQOL) and treatment autoimmune bullous
diseases quality of life (TABQOL);
• mean reduction of Bullous Pemphigoid Disease Area Index (BPDAI).
Background summary
Pemphigoid is the most common chronic autoimmune disease of the skin and
mucosae. It is characterized by subepidermal blistering caused by
autoantibodies directed against hemidesmosomal proteins BP180 and BP230 located
in the basement membrane zone.
Pemphigoid is often treated with systemic corticosteroids. In the absence of
treatment, pemphigoid has a tendency to relapse. Systemic corticosteroids
however, are associated with serious adverse effects, morbidity and mortality.
Therefore, there is a need for safer treatment options. In this pilot efficacy
study the treatment response of apremilast combined with doxycycline in mild to
moderate cutaneous pemphigoid will be evaluated. We hypothesize an impairment
of immune-complex-induced neutrophil activation caused by PDE4 inhibition,
making it a potential target for the treatment of pemphigoid diseases. This is
based on the facts that PDE4 is the key enzyme accounting for cAMP degradation
in neutrophils and PDE4 inhibitors are highly effective to curb neutrophil
functions. An animal study showed reduction in blistering by PDE4 inhibitors
in antibody transfer-induced epidermolysis bullosa acquisita and also hindered
disease progression in immunization-induced epidermolysis bullosa acquisita.
Study objective
Primary Objective:
To evaluate the achievement of partial remission by apremilast combined with
doxycycline
at week sixteen (t=16).
Secondary Objectives:
• Complete remission at week sixteen;
• Disease control at week six (t=6);
• Drug survival;
• Clinical efficacy;
• Mean decrease in periphery blood eosinophil count;
• Mean decrease in BP180 Nc16a titers by ELISA;
• Change in genexpression by RNA sequencing measured at t=0 and t=16.
Study design
This is an open label, single arm study in 10 patients with pemphigoid.
Intervention
Investigational product: apremilast (Otezla)
Non-investigational product: doxycycline
Included subject will be treated with doxycycline during 6 weeks and
apremilast during 16 weeks.
Study burden and risks
Eligble patients will be recruited during routine clinical care. There is a
total of 7 visits. The patients will undergo a screening which forms part of
the inclusion phase. All patients will be screened for hepatitis B and C, HIV
and tuberculosis (TBC) by blood test. Moreover, an X ray will be performed for
TBC screening before starting therapy. Fertile female participants will undergo
a serum pregnancy test. At screening, patients will have their medical history
taken and will undergo a physical exam by a physician including measuring vital
signs (blood pressure, heart rate, temperature). This will be taken every visit
including VAS, BPDAI score and checking for adverse events. Moreover,
photodocumentation will be taken at every visit. Laboratory tests will be taken
at baseline, week 6 and week 16, and if necessary on indication during other
visits. At baseline and week 16 two perilesional punch biopsy will be taken.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
adult (>= 18 years of age) male or female patients with recently diagnosed mild
to moderate localized or generalized cutaneous pemphigoid, or patients that
were in complete remission without treatment that have a mild to moderate
flare-up of the disease.
Exclusion criteria
Women of childbearing potential without contraception; women who are pregnant
or planning to become pregnant or who are lactating; patients that use systemic
immunosuppressive medication provided the treatment cannot be stopped before
Visit 2; any condition which would make the patient unsuitable for treatment,
or requires steroid use. Patients with PHQ-9 (Patients Health Questionnaire-9)
score >= 10. Contradiction or known allergy for PDE4 inhibitors;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002564-10-NL |
| CCMO | NL66819.042.18 |