Short-term Safety, Efficacy and Mode of Action of Apremilast in Moderate Suppurative Hidradenitis

Hidradenitis Suppurativa Clinical Trial

— SMASH  

Official title:

Short-term Safety, Efficacy and Mode of Action of Apremilast in Moderate Suppurative Hidradenitis: A Randomised Double-blind Placebo Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03049267
• Other study ID #: SMASH trial
• Status: Completed
• Phase: Phase 2
• Start date: February 2, 2017
• Est. completion date: June 28, 2018

Study information

• Verified date: July 2018
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study design: A double-blind randomised placebo-controlled trial

Intervention: Randomized placebo controlled treatment of 20 HS patients of which fifteen patients will be randomized to apremilast and five patients to placebo. The total duration of the treatment period per subject is 16 weeks.

Primary objectives: To evaluate the expression profile of inflammatory cytokines in HS lesional skin at week four (t=4) and week sixteen (t=16):

• of patients receiving apremilast compared to placebo;

• within both groups relative to baseline (t=0).

Secondary objectives:

• To prospectively evaluate the clinical efficacy of apremilast.

• To assess the effect of apremilast on patient reported outcomes measures.

• To assess the short-term safety and tolerability of apremilast in patients with hidradenitis suppurativa.

Description:

Rationale:

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. It is characterized by painful, deep-seated, inflamed boils in the inverse areas of the body, most commonly the axillae, inguinal and anogenital regions.

Systemic therapy with immunosuppressive agents (systemic corticosteroids, dapsone, cyclosporin) has been investigated in the past decades and has shown limited efficacy. The use of the selective immunosuppressant apremilast has not yet been evaluated in HS. The investigators hypothesize a beneficial effect of apremilast in HS patients, similar to the efficacy of apremilast in psoriasis patients. Namely, it has been shown that the immune dysregulation in the pathogenesis of HS shows many similarities with that of psoriasis. Moreover, the TNF-α blocker adalimumab was registered for HS after approval for the treatment in patients with psoriasis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 28, 2018
• Est. primary completion date: December 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key inclusion criteria:

• Adult (= 18 years of age) male or female patients with moderate HS according to a PGA of 3 on the 5-point HS-Physician Global Assessment (HS-PGA);

• HS of more than 6 months duration; have lesions in at least two anatomical locations.

Key exclusion criteria:

• Contra-indication for apremilast; previous use of apremilast; have any current and/or recurrent clinically significant skin condition in the treatment area other than HS;

• Presence of other uncontrolled major disease;

• Pregnant or lactating women.

Related Conditions & MeSH terms

• Hidradenitis
• Hidradenitis Suppurativa

Intervention

Drug:
• Apremilast
Fifteen patients will be supplied of apremilast for daily oral use; 16 weeks.
• Placebo Oral Tablet
Five patients will be supplied with placebo tablets with identical labeling as apremilast for daily use; 16 weeks.

Locations

Country	Name	City	State
Netherlands	Erasmus University Medical Center	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
M.B.A. van Doorn	Celgene

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of expression levels of inflammatory cytokine mRNA in HS lesional skin.	measurement by qPCR	t=16 weeks
Primary	Change of expression levels of inflammatory cytokine protein in HS lesional skin.	measurement by ELISA	t=16 weeks
Secondary	Abscesses count	Total number of abscesses [A]	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Nodule count	Total number of inflammatory [N] and non-inflammatory nodules	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Fistula count	Total count of draining fistulas	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) score	Based on the HS lesion count	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Hidradenitis Suppurativa Clinical Response (HiSCR)	Based on the AN count; The proposed definition of 50% and 30% responders to treatment (HiSCR achievers) is respectively: (i) at least a 50% and 30% reduction in ANs, (ii) no increase in the number of abscesses, and (iii) no increase in the number of draining fistulas from baseline.	t=0 weeks, t=16 weeks
Secondary	Numerical Rating Scale (NRS)	To assess the patient reported outcome measures (PROMs) pain, pruritus and patient disease global assessment score;	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Dermatology Life Quality Index (DLQI)	To assess the patient reported outcome measures (PROM) quality of life	t=0 weeks, t=4 weeks, t=16 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events	Vital signs: heart rate, temperature, blood pressure. Patient reported adverse events Safety laboratories: White blood cell count, Absolute neutrophil count, Hemoglobin, Platelets, Serum Creatinine, ALT, Alkaline phosphatase	Multiple time points between t=0 weeks and t=16 weeks