To assess the safety, tolerability, pharmacodynamics and efficacy of two DLQ02 topical formulations in patients with plaque psoriasis. To assess systemic exposure of CsA and F6H8 after topical application.
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / safety endpoints
1) Adverse events (AE)
2) Laboratory safety testing (blood and urine)
3) 12-lead ECGs
4) Vital signs
5) Physical examination
6) Systemic levels of CsA and the novel excipient F6H8
7) Skin irritation of non-lesional skin by local irritation grading scale
(LIGS) (Part A only)
Adherence
Electronic diary with photo capture function to monitor treatment compliance.
Secondary outcome
Pharmacokinetic endpoints
1) Cutaneous PK in skin biopsies.
2) Systemic levels of CsA and the novel excipient F6H8
Pharmacodynamic and efficacy endpoints
1) Severity of psoriasis target lesion after 1, 2, 3 and 4 weeks of treatment
using clinical assessment of signs (erythema, induration, scaling) expressed as
TSS (Total Sum Score)
2) Percent of patients achieving clinical scores of the target lesion of clear
(score of 0 for each symptom) or almost clear (erythema, induration and scaling
each <=1) at week 4.
3) Score for individual symptoms of the target lesion (erythema, induration and
scaling) after 1, 2, 3 and 4 weeks of treatment
4) Target lesion area assessed by 2D photography analysis after 1, 2, 3 and 4
weeks of treatment
5) Target lesion erythema assessed by multispectral/3D photography after 1, 2,
3 and 4 weeks of treatment
6) Target lesion roughness assessed by multispectral/3D photography after 1, 2,
3 and 4 weeks of treatment
7) Patient reported itch of the target lesion (twice daily NRS by e-diary)
after 1, 2, 3 and 4 weeks of treatment
8) Target lesions thickness assessed by Optical Coherence Tomography (OCT)
(lesional and non-lesional) after 1, 2, 3, and 4 weeks of treatment.
9) Microcirculation of the target lesion assessed by Laser Speckle Contrast
Imaging (LSCI) after 1, 2, 3 and 4 weeks of treatment
10) Skin surface biomarkers by FibroTX Patch, after 1, 2, 3 and 4 weeks of
treatment
11) Transepidermal water loss assessed by Aquaflux and GPskin, after 1, 2, 3,
4, weeks of treatment.
12) Skin pH assessed by Courage and Khazaka pH meter after 1,2,3, and 4 weeks
of treatment.
13) Digital PASI score assessed with total body photography at baseline, end of
treatment and at end of study.
Background summary
Psoriasis is a common skin disorder affecting up to an estimated 3% of the
world*s population. The most prevalent form of psoriasis, psoriasis vulgaris or
plaque psoriasis, is characterized by the presence of sharply demarcated
erythematous plaques covered with white scales. These lesions can occur all
over the body but are most often seen on the extensor surface of the joints,
nether regions and on the scalp. Patients can experience excessive itch, pain
and sometimes bleeding of the lesions. Moreover, the visual appearance of
psoriatic lesions can severely impact the patients* psychological state and
quality of life (Boehncke and Schön, 2015).
An abundancy of different factors contributes to the pathogenesis of psoriasis.
However, aberrant activation of inflammatory pathways in the skin are thought
to be the underlying cause. Excessive infiltration of immune (T)-cells in the
skin and their interactions with cutaneous resident immune cells results in the
hyperproliferation of keratinocytes and subsequent thickening of the epidermis.
Because of the importance of the inflammatory reaction in the pathogenesis of
psoriasis, one of the treatments that can be prescribed is the
immunosuppressive drug Cyclosporine A, a calcineurin inhibitor. Cyclosporine A
(CsA) is a cyclic polypeptide with a strong immunosuppressive effect by
reversibly blocking T-cell proliferation. Currently CsA is available only as an
oral solution. The side effect profile of CsA includes nausea, hypertension and
nephrotoxicity, of which the latter can be irreversible. A topical CsA drug
product would have great advantage in the treatment of psoriasis, as the drug
will be applied directly to the target tissue and it is expected that there
will be no or only minimal systemic exposure. This concept has been
investigated in previous studies, however none of these investigations were
successful in delivering Cyclosporine across the stratum corneum.
Dermaliq has developed a novel topical drug product candidate of CsA: DLQ02, a
liquid formulation with the target to facilitate dermal delivery of the active
compound to the target tissues.
In this phase I/IIa study the safety, tolerability, pharmacodynamics and
efficacy of two dose strengths of DLQ02 will be assessed when applied BID to
one target lesion for four weeks in 36 patients with plaque psoriasis.
Study objective
To assess the safety, tolerability, pharmacodynamics and efficacy of two DLQ02
topical formulations in patients with plaque psoriasis.
To assess systemic exposure of CsA and F6H8 after topical application.
Study design
Phase I/IIa, single-centre, randomized, double-blind, vehicle-controlled study
with a safety run-in period. The study will entail two parts. The aim of part A
is to closely observe the safety through daily assessments of both the lesional
and non-lesional skin whereas Part B is only focussing on lesional skin.
Intervention
DLQ02 is a liquid topical drug product with CsA as active. In this study two
Cyclosporine concentrations (0.2% and 1.0%) will be assessed.
Study burden and risks
DQL02 is expected to have a local immunosuppressive effect associated with the
active ingredient CsA. The risks associated with the topical administration of
DQL02 to humans have not yet been identified, because this compound has not yet
been applied to the skin of humans. However, the effect of the excipient F6H8
on the eye has been studied in 5 clinical trials, and has shown excellent
in-use tolerability. The eye itself is extremely sensitive to irritating
substances and following the application of drops to the eye there is often
smearing to the sensitive skin around the eye. Therefore, the ocular safety of
F6H8 is considered a sensitive indicator for irritation that may occur
following topical administration of F6H8 to the skin. Risks associated with
systemic CsA treatment are amongst others nephrotoxicity and hypertension. This
is not expected with DLQ02 as systemic exposure is unlikely and the maximum
dose is 29 times lower than the maximum allowed dose for systemic cyclosporine.
1201 North Market Street Suite 111
Wilmington DE 19801
NL
1201 North Market Street Suite 111
Wilmington DE 19801
NL
Listed location countries
Age
Inclusion criteria
Patients must:
1) Be males or non-pregnant, non-lactating females.
2) Be at least 18 years of age at time of consent.
3) Have stable psoriatic plaque psoriasis (for >= 6 months), as confirmed by the
patient.
4) Have a maximum (treatable) BSA of 2.5% (only part B)
5) Have a target plaque (area) suitable for treatment >=15cm2 and <=100cm2 with a
severity defined by TSS score >= 4, with at least a clinical score of >= 2 for
either erythema or induration and >=1 for the symptom scaling.
6) Be able and willing to follow instructions and comply with the study
restrictions, including participation in all trial assessments and visits.
7) Provide written informed consent.
8) Be willing to refrain from medications for psoriasis according to the
wash-out periods.
9) Patients and their partners of childbearing potential must use effective
contraception, for the duration of the study and for 3 months after the last
dose.
Exclusion criteria
Patients must not:
1) Have any current and / or recurrent clinically significant skin condition
which will interfere with the clinical findings of the study as assessed by the
investigator.
2) Have a current diagnosis of psoriasis other than plaque psoriasis (including
guttate psoriasis, psoriasis erythroderma and pustular psoriasis).
3) Use the following psoriasis medications. Wash-out periods are stated below.
• Local treatment of plaques with anti-psoriatics (e.g., vitamin D analogs,
corticosteroids, retinoids, tacrolimus or other calcineurin inhibitors
excepting CsA (prohibited): 2 weeks prior to baseline.
• Emollients or scale-softening treatments on target plaques (including
salicylic acid): from baseline onwards.
4) Have a current systemic treatment with psoriasis medication (e.g. retinoids
and immunomodulating drugs such as methotrexate and tacrolimus, CsA or a
treatment with biologic.)
5) Begin treatment with systemic or locally acting medications which might
counter or influence the study aim (e.g., medications which are known to
provoke or aggravate psoriasis including but not limited to antimalarial drugs,
beta-blockers [e.g., propanolol], lithium, iodides, angiotensin-converting
enzyme inhibitors, nifepidine, indomethacin, ciprofloxacin, and
diphenhydramine) prior to baseline (therapy with stable dose is allowed).
6) Begin treatment with CYP3A4 interactive drugs [e.g., miconazole,
ketoconazole, erythromycin, clarithromycin, diltiazem, ritonavir, verapamil,
grapefruit].
7) Have history of PUVA if >1000 J/cm2 or >200 cumulative treatments.
8) Have participated in a clinical research trial within 90 days, or 5
half-lives of the investigational product, whichever is greater, prior to
screening visit.
9) Be study site employees, or immediate family members of a study site or
sponsor employee.
10) Have prolonged exposure to UV light within two weeks prior to study day 1
or intention to have such exposures during the study.
11) Have a history of drug abuse within the past two years.
12) Regular alcohol consumption in males >21 units per week and females>14
units per week (1 unit approximately 240 ml of beer, 25 ml of 40% spirit or a
125 ml glass of wine), or a history of alcohol abuse within the past two years.
13) Change smoking habits during the 4 weeks prior to study start or during the
study; smokers are allowed up to 6 cigarettes per day if smoking is a current
habit.
14) Have clinically significant abnormal biochemistry, hematology or urinalysis
as judged by the investigator.
15) Have liver function tests (ALT, AST, GGT, ALP) range >2.5 X upper limit of
normal of each parameter at screening.
16) Have a clinically significant abnormal renal function (including any stage
of chronic kidney disease).
17) Have positive hepatitis B surface antigen (HBsAg), hepatitis C virus
antibody (HCV Ab), or human immunodeficiency virus (HIV) results.
18) Have live vaccination during the study or in the 2 weeks before study start.
19) Have vaccination for SARS-CoV-2 within 14 days prior to initial dosing, or
planned during the course of the study.
20) Have history of malignancy, except adequately treated non-invasive skin
cancer (basal or squamous cell carcinoma).
21) Have clinically significant illness or infection that may, in the opinion
of the investigator, contraindicate participation in the trial or interfere
with the outcome of the trial in the 4 weeks before the baseline visit and
during the trial.
22) Have history of sensitivity to any of the study medications, or components
thereof, or a history of drug or other allergy that, in the opinion of the
investigator or medical monitor, contraindicates participation.
23) Have clinically significant uncontrolled hypertension as judged by the
investigator (stable treatment is allowed).
24) Fail to satisfy the investigator of fitness to participate in the trial for
any other reason.
25) Have loss or donation of blood over 500 mL within three months (males) or
four months (females) prior to screening.
26) Have used Evotears® or Novatears® one week before Day 1 or plan to use it
during the course of the trial
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 | EUCTR202200107113-NL |
| CCMO | NL80977.056.22 |