The objective of the present phase 2 trial is to evaluate the safety, pharmacodynamics (effect on HPA axis and calcium metabolism) and pharmacokinetics of LEO 90100 in adolescent subjects with plaque psoriasis. Subjects will be treated once daily…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Adverse events (AEs)
* Subjects with serum cortisol concentration of <=18 mcg/dl at 30 minutes after
ACTHchallenge at Week 4
* Change in albumin-corrected serum calcium from baseline (SV2) to Week 4
* Change in calcium excretion from baseline (SV2) to Week 4 in 24-hour urine
* Change in calcium:creatinine ratio from baseline (SV2) to Week 4 in 24-hour
urine
Secondary outcome
* Subjects with serum cortisol concentration of <=18 mcg/dl at both 30 and 60
minutes after ACTH-challenge at Week 4
* Change in calcium:creatinine ratio from baseline (SV2) to Week 4 in spot urine
* Subjects with *treatment success* (i.e., *clear* or *almost clear* for
subjects with at least *moderate* disease at baseline, *clear* for subjects
with *mild* disease at baseline) according to the physician*s global assessment
of disease severity on the body at Week 4
* Subjects with *treatment success* (i.e., *clear* or *almost clear* for
subjects with at least *moderate* disease at baseline, *clear* for subjects
with *mild* disease at baseline) according to the physician*s global assessment
of disease severity on the scalp at Week 4
* Percentage change in psoriasis area and severity index (PASI) from baseline
(V1) to Week 4
* Subjects with *treatment success* (i.e., *clear* or *very mild) according to
the subject*s global assessment of disease severity on the body at Week 4
* Subjects with *treatment success* (i.e., *clear* or *very mild) according to
the subject*s global assessment of disease severity on the scalp at Week 4
* Change in itch as assessed by the Visual Analogue Scale (VAS) from baseline
(V1) to Week 4
Background summary
The majority of affected subjects has mild to moderate disease and can be
treated with topical therapies. In the group of subjects with moderate to
severe psoriasis topical therapies are also appropriate either as adjunct to
phototherapy, systemic or biologic agents. One of the advantages of topical
therapies is a reduced risk of systemic toxicity compared to other treatment
modalities. The most commonly used topical therapies in adults are
corticosteroids and vitamin D analogues used either alone or in combination.
The fixed combination of calcipotriol 50 mcg/g (as monohydrate) and
betamethasone 0.5 mg/g (as dipropionate) in an ointment and gel/topical
suspension formulation for body and scalp have already been marketed for
several years in adults. These products are marketed in the US under the trade
name Taclonex® and in Europe under trade names such as Daivobet®, Dovobet® and
Xamiol®. FDA has recently granted approvals for the treatment of scalp
psoriasis with Taclonex® Topical suspension in adolescent patients aged 12-17
years and treatment of psoriasis vulgaris with Taclonex® Ointment in adolescent
patients aged 12-17 years.
Psoriasis is a chronic, recurrent disease, and no cure exists. Despite
availability of current treatment options, many subjects are not achieving
optimal control of their psoriasis. Patient adherence may be the largest
barrier to treatment success with topical therapies. The factors
that hinder patient adherence include frustration with medication efficacy,
messiness and time-consuming and inconvenient application, among others.
To address this need, LEO has developed a new formulation of
calcipotriol/betamethasone dipropionate (BDP) which was demonstrated to be more
effective than Daivobet ® ointment with a similar safety profile in adults,
including systemic safety. The foam formulation may be cosmetically more
acceptable and user friendly than ointment and therefore potentially lead to
better adherence.
Study objective
The objective of the present phase 2 trial is to evaluate the safety,
pharmacodynamics (effect on HPA axis and calcium metabolism) and
pharmacokinetics of LEO 90100 in adolescent subjects with plaque psoriasis.
Subjects will be treated once daily over a period of 4 weeks.
Study design
This will be an international, multi-centre, prospective, open-label ,
non-controlled, singlegroup, 4-week trial in adolescent subjects (aged 12 to <
17 years) with plaque psoriasis on the body and scalp.
De patiënten zullen plaatselijke behandeling ontvangen met LEO 90100 een maal
per dag voor maximaal 4 weken. De onderzoeksduur van elke patiënt (inclusief
een 4-weekse uitwasperiode) is 8 weken en omvat 5 bezoeken aan de kliniek (tot
7 keer als er een follow-up bezoek is vereist).
Intervention
See Study population (in English)
Study burden and risks
If your child participates in this study, he or she will receive a new drug.
Little is known about the effects and side effects of this medicine in
children. This is a disadvantage. If the treatment improves the disorder, this
will be an advantage.
Research on blood samples of your child's supplies may not directly benefit
your child. However, the information may be useful in order to develop new
treatments for psoriasis and identify patients who can benefit from treatment
in the future.
Industriparken 55
Ballerup 2750
DK
Industriparken 55
Ballerup 2750
DK
Listed location countries
Age
Inclusion criteria
Main criteria for inclusion (all subjects)
- Adolescent subjects (age 12 to 16 years, 11 months).
- Plaque psoriasis on trunk and/or limbs affecting at least 2% BSA.
- Plaque psoriasis on the scalp affecting at least 10% of total scalp area.
- A total psoriatic involvement on trunk, limbs and scalp not exceeding 30% BSA.
- PGA score of at least mild on trunk and/or limbs at SV1, SV2 and V1.
- PGA score of at least mild on scalp at SV1, SV2 and V1.
- A serum albumin-corrected calcium below the upper reference limit at SV2.
- Female subjects must be of either
* non-childbearing potential, i.e. premenarchal or have a confirmed clinical history of
sterility (e.g. the subject is without a uterus or has tubal litigation) or,
* child-bearing potential provided there is a confirmed negative pregnancy test prior to
trial treatment to rule out pregnancy.
- Female subjects of child-bearing potential must be willing to use highly effective contraception at trial entry and until completion.;Main criteria for inclusion (for subjects undergoing HPA axis testing:)
- Plaque psoriasis on trunk and/or limbs affecting at least 10% BSA.
- Plaque psoriasis on the scalp affecting at least 20% of total scalp area.
- PGA score of at least moderate on trunk and limbs at SV1, SV2 and V1.
- PGA score of at least moderate on scalp at SV1, SV2 and V1.
- Normal HPA axis function at SV2 (serum cortisol concentration above 5 mcg/dl before ACTH challenge and serum cortisol concentration above 18 mcg/dl 30 minutes after ACTH challenge).
Exclusion criteria
Main criteria for exclusion (for all subjects):
- A history of hypersensitivity to any component of LEO 90100.
- Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on scalp and/or body psoriasis within the following time period prior to V1 and during the trial:
a. etanercept - within 4 weeks prior to V1
b. adalimumab, infliximab - within 2 months prior to V1
c. ustekinumab - within 4 months prior to V1
d. experimental products - within 4 weeks/5 half-lives (whichever is longer) prior to V1
- Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g. methotrexate, retinoids, immunosuppressants) within 4 weeks prior to V1 or during the trial.
- PUVA therapy within 4 weeks prior to V1.
- UVB therapy within 2 weeks prior to V1 or during the trial.
- Any topical treatment on the scalp and body including corticosteroids and vitamin D (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to V1 or during the trial.
- Systemic calcium, vitamin D supplementation > 400 IU/day, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial. (note: stable dose of vitamin D supplementation <= 400 IU/day is permitted provided there are no dose adjustments during the study period).;Main criteria for exclusion (for subjects undergoing HPA axis testing:)
- A history of serious allergy, allergic asthma or serious allergic skin rash.
- Known or suspected hypersensitivity to any component of CORTROSYN®/Synacthen®(including ACTH/cosyntropin/tetracosactide)
- Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
- Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to SV2 or during the trial.
- Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the trial.
- Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole,metronidazole) within 4 weeks prior to SV2 or during the trial. Topical ketoconazole within 2 weeks prior to SV2.
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 | EUCTR2015-000839-33-NL |
| ClinicalTrials.gov | NCT02387853 |
| CCMO | NL54553.091.15 |