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

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

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.

Study Overview

• Status: Completed
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo Oral Tablet

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Erasmus University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast; N=15	Drug: Apremilast; Fifteen patients will be supplied of apremilast for daily oral use; 16 weeks.; Other Names: Otezla, CC-10004
Placebo Comparator: Placebo Oral Tablet; N=5	Drug: Placebo Oral Tablet; Five patients will be supplied with placebo tablets with identical labeling as apremilast for daily use; 16 weeks.; Other Names: Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of expression levels of inflammatory cytokine mRNA in HS lesional skin.	measurement by qPCR	t=16 weeks
Change of expression levels of inflammatory cytokine protein in HS lesional skin.	measurement by ELISA	t=16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abscesses count	Total number of abscesses [A]	t=0 weeks, t=4 weeks, t=16 weeks
Nodule count	Total number of inflammatory [N] and non-inflammatory nodules	t=0 weeks, t=4 weeks, t=16 weeks
Fistula count	Total count of draining fistulas	t=0 weeks, t=4 weeks, t=16 weeks
Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) score	Based on the HS lesion count	t=0 weeks, t=4 weeks, t=16 weeks
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
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
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
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

Collaborators and Investigators

• Sponsor: M.B.A. van Doorn
• Collaborators: Celgene
• Investigators: Principal Investigator: Errol Prens, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): December 6, 2017
• Study Completion (Actual): June 28, 2018

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Actual): February 10, 2017

Study Record Updates

• Last Update Posted (Actual): July 24, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: acne inversa
• Additional Relevant MeSH Terms: Sweat Gland Diseases; Skin Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Hidradenitis Suppurativa; Hidradenitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: SMASH trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes