Laser-assisted Topical Administration of Etanercept (Enbrel®) in Patients With Mild to Moderate Plaque-type Psoriasis

NCT02999776 | Unknown Phase 1 DMC

• 1 other identifier: TopPso-2015
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the feasibility and safety of topical administration of etanercept via AFL micropores to psoriatic plaques in patients with mild to moderate plaque-type psoriasis. While a wide variety of therapeutic innovations to treat moderate-to-severe psoriasis (accounting for around 30% of the cases) become available each year, there are few innovations for topical therapies to treat mild/localized psoriasis (accounting for around 70% of the cases). Given that only about half of the patients respond adequately to the current standard of care, the topical application of a fixed combination of calcipotriole and betamethasone, there is a medical need for better topical therapies. Etanercept has been used successfully to treat moderate-to-severe plaque-type psoriasis in children and adults for more than a decade. Its standard route of application is through subcutaneous injections. Different dosing regimens have been used: 1 x 50 mg or 2 x 50 mg per week as well as 1 x 25 mg or 2 x 25 mg per week. Under these regimens, etanercept has a well-established favorable long-term safety record, with injection site reactions (pain, swelling) the most frequently reported side effects. However, rare but serious side effects such as serious opportunistic infections resulting from immune system inhibition common to anti-TNF agents limit its systemic use to these patients. For this reason, a localized topical alternative route of administration would be desirable. However, the large molecular size and chemical nature of etanercept prevent it from crossing the epidermal barrier. A CE certified ablative fractional laser (AFL) device with Er:YAG source will be used to create micropores in plaques to allow local delivery of etanercept directly into psoriatic plaques.

Conditions

Psoriatic Plaque

Keywords

Plaques Psoriasis; Topical; Laser microporation

Outcome Measures

Primary Outcomes (1)

• Administration site reactions (ASR)

  The investigator or qualified designee will assess ASRs such as itching, redness, swelling, pain, or ulceration at time points as indicated in Table 6-1. Whenever possible, the same evaluator should perform this assessment at all visits and document the result in the eCRF. An ASR that fulfills the criteria of an SAE should be documented and reported as such.

  8 weeks

Secondary Outcomes (1)

• Target Plaque Severity Score (TPSS)

  8 weeks

Study Arms (3)

Standard of care

ACTIVE COMPARATOR

Daily self-administration of 1 to 5g Daivobet (Calcipotriol 50ug/g +Betamethasone, 0,5mg/g Gel) ointment, which is applied topically once per day for 8 weeks on one pre-selected randomized plaque.

Drug: Standard of care-daily administration of Daivobet

Laser plus etanercept

EXPERIMENTAL

Immediately following microporation of a 5 cm² area of the designated plaque with the P.L.E.A.S.E.® Professional laser, 0.0625 ml of Etanercept (50 mg/ml) solution for injection in pre-filled syringes will be applied to the microporated surface of the lesion. The treated area will then be covered with OpSiteTM Flexigrid Transparent Dressing for 4 hours. This treatment procedure will be repeated twice weekly for 8 weeks.

Drug: Laser microporation + topical application of Etanercept

Laser alone

ACTIVE COMPARATOR

The Er:YAG laser induced microporation of 5 cm2 of a plaque surface, followed by application of an OpSiteTM Flexigrid Transparent Dressing for 4 hours. This treatment will also be repeated twice weekly for 8 weeks.

Device: Laser microporation alone

Interventions

Laser microporation alone DEVICE

The Er:YAG laser induced microporation of 5 cm2 of a plaque surface, followed by application of an OpSiteTM Flexigrid Transparent Dressing for 4 hours. This treatment will also be repeated twice weekly for 8 weeks.

Also known as: P.L.E.A.S.E.

Laser alone

Standard of care-daily administration of Daivobet DRUG

The other control treatment is Daivobet®, which is applied topically daily for 8 weeks on one pre-selected randomized plaque.

Also known as: Daivobet

Standard of care

Laser microporation + topical application of Etanercept DRUG

Immediately following microporation of a 5 cm² area of the designated plaque with the P.L.E.A.S.E.® Professional laser, 0.0625 ml of Etanercept (50 mg/ml) solution for injection in pre-filled syringes will be applied to the microporated surface of the lesion. The treated area will then be covered with OpSiteTM Flexigrid Transparent Dressing for 4 hours. This treatment procedure will be repeated twice weekly for 8 weeks.

Also known as: Etanercept

Laser plus etanercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed.
• Men or women, non-pregnant and non-lactating, at least 18 years of age at time of screening
• Chronic mild to moderate plaque-type psoriasis diagnosed at least 6 months prior to baseline. Chronic mild to moderate plaque-type psoriasis as defined at screening by:
• BSA affected by plaque-type psoriasis of less than 10%
• Eligible for topical therapy according to current psoriasis treatment guidelines (12).

You may not qualify if:

• Forms of psoriasis other than mild to moderate plaque-type (e.g., pustular, erythrodermic and guttate psoriasis)
• Hyperpigmentation, e.g. birth marks, freckles, scar tissue at the psoriasis plaque areas that are intended to be treated
• Intertriginous plaques or plaques on the hands, feet, neck, face, elbows, knees, or on the scalp will not be eligible as plaques for treatment.
• Plaques on eyelids, lips or mucous membranes, open wounds, moles or birth marks, areas at risk of developing post-inflammatory hypo- or hyperpigmentation due to high levels of UV radiation subsequent to treatment will not be eligible for treatment.
• Drug-induced psoriasis (i.e., new onset or current exacerbation from e.g. beta-blockers, or lithium)
• Ongoing use of prohibited psoriasis treatments (e.g., topical corticosteroids, UV-therapy). Washout periods detailed in the protocol have to be adhered to (see Table 5-2)
• Ongoing use of other non-psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to (see Table 5-2). All other prior non-psoriasis concomitant treatments must be on a stable dose for at least four weeks before baseline
• Use of any other investigational drugs within 30 days prior to screening (or within 5 half-lives or until the expected PD effect has returned to baseline, whichever is longer).
• Requiring treatment with any biological medicinal product during the study other than the study medication.
• Any contraindication to etanercept (Enbrel®) or calcipotriol/betamethasone (Daivobet®).
• Previous (last 12 months) and current exposure biologics, such as etanercept, adalimumab.
• Any contraindication to treatment with the P.L.E.A.S.E® device, including Fitzpatrick skin types V or VI.
• Current treatment or need for treatment with any prohibited medications (listed under Section 5.9.6).
• Any serious illness or uncontrolled medical condition, including but not limited to severe infections, significant hepatic or renal disease, uncontrolled hypertension (defined as blood pressure ≥160/95), congestive heart failure (NYHA class III or IV), or other severe, uncontrolled cardiac disease.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (cut-off as defined by laboratory)

Sponsors & Collaborators

• Pantec Biosolutions AG: lead

Study Sites (1)

University Hospital Geneva

Geneva, 41205, Switzerland

RECRUITING

MeSH Terms

Interventions

betamethasone dipropionate, calcipotriol drug combination; Etanercept

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Wolf-Henning Boehncke, Prof.

  HUG

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wolf-Henning Boehncke, Prof.

CONTACT

+41(0)22 372 94 22; wolf-henning.boehncke@hcuge.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 21, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: December 21, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)