Clinical trial NCT02038569: An International, Multi-centre, Prospective, Non-controlled, Open, Single-group, 8-week Trial in Adolescent Subjects
Official title: Effect of Calcipotriol Plus Betamethasone Dipropionate Gel on the HPA Axis and Calcium Metabolism in Adolescent Subjects (Aged 12 to 16 Years, 11 Months) With Scalp and Body Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis Vulgaris
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2014-01-16
Enrollment: 125
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An international, multi-centre, prospective, non-controlled, open, single-group, 8-week trial in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.

Detailed description: A phase 2 trial evaluating the safety and efficacy of once daily use of LEO 80185 gel containing calcipotriol 50 mcg/g plus betamethasone 0.5mg/g (as dipropionate) in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.

Eligibility criteria: Inclusion Criteria (all subjects):

* Clinical signs of psoriasis vulgaris on both the scalp and body (trunk and/or limbs)
* At SV2 and Visit 1, a clinical diagnosis of scalp and body (trunk and/or limbs) psoriasis which is:

  * of an extent of 10 to 35% of the body surface area (excluding psoriatic lesions of the face and sensitive areas. Sensitive areas include armpits, groin, under the breasts and in other skin folds around the genitals and buttocks), and
  * of at least moderate severity according to the investigator's global assessment of disease severity on the body.
* A serum albumin-corrected calcium level below the upper reference limit at SV2

Inclusion Criteria (for subjects performing HPA axis assessments):

* At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:

  * more than or equal to 20% of the scalp area, and
  * of at least moderate severity according to the investigator's global assessment of disease severity on the scalp.
* Subjects with a normal HPA axis function at SV2 including serum cortisol concentration above 5 mcg/dl before ACTH challenge and serum cortisol concentration above 18 mcg/dl 30 minutes after ACTH challenge.

Inclusion Criteria (for subjects not performing HPA axis assessments):

* At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:

  * more than or equal to 10% of the scalp area, and
  * of at least moderate severity according to the investigator's global assessment of disease severity on the scalp.

Exclusion Criteria (all subjects):

* 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 Visit 1 and during the trial:

  * etanercept - within 4 weeks prior to Visit 1
  * adalimumab, infliximab - within 2 months prior to Visit 1
  * ustekinumab - within 4 months prior to Visit 1
  * experimental products - within 4 weeks/5 half-lives (whichever is longer) prior to Visit 1
* Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g., retinoids, immunosuppressants, PUVA) within 4 weeks prior to Visit 1 (Day 0) or during the trial.
* UVB therapy within 2 weeks prior to Visit 1 or during the trial.
* Any topical treatment on the scalp and body (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to Visit 1 or during the trial.
* Systemic calcium, vitamin D supplements, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial.
* Planned initiation of, or changes to, concomitant medication that could affect psoriasis (e.g., betablockers, chloroquine, lithium, ACE inhibitors) during the trial.
* Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.
* Subjects with any of the following conditions present on the treatment areas on scalp and/or body: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, acne vulgaris, acne rosacea, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers and wounds.
* Other inflammatory skin diseases that may confound the evaluation of scalp and/or body psoriasis.
* Planned excessive exposure to sun during the trial that may affect scalp and/or body psoriasis.
* Known or suspected severe renal insufficiency or severe hepatic disorders.
* Known or suspected disorders of calcium metabolism associated with hypercalcaemia.
* Any clinically significant abnormality following review of screening laboratory tests (blood and urine samples), physical examination or blood pressure/heart rate measurement performed at SV2.
* Current participation in any other interventional clinical trial.
* Previously enrolled in this trial.
* Subjects who have received treatment with any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within a month prior to SV1 or longer, if the class of substance required a longer wash-out as defined above (e.g., biological treatments).
* Subjects or parent(s) or legal guardian known or suspected of being unlikely to comply with the Clinical Trial Protocol (e.g., alcoholism, drug dependency or psychotic state).
* Females who are pregnant, or of child-bearing potential and wishing to become pregnant during the trial, or who are breast-feeding.
* Females of child-bearing potential with positive pregnancy test at SV2.
* Subject (or their partner) not using an adequate method of contraception according to national requirements.

Exclusion Criteria (for subjects performing HPA axis assessments)

* A history of serious allergy, allergic asthma or serious allergic skin rash.
* Known or suspected hypersensitivity to any component of CORTROSYN® (including ACTH/cosyntropin/tetracosactide)
* Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
* Topical treatment with corticosteroids within 2 weeks prior to SV2 or during the trial.
* Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels 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 2 weeks prior to SV2.
* Hypoglycemic sulfonamides within 4 weeks prior to SV2 or during the trial.
* Antidepressive medications within 4 weeks prior to SV2 or during the trial.
* Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
* Clinical signs or symptoms of Cushing's disease or Addison's disease.
* Subjects with diabetes mellitus.
* Known or suspected cardiac condition.
* Not following nocturnal sleep patterns.

Primary outcomes:
measure: Adverse Drug Reactions (ADRs)
timeFrame: 8 weeks
measure: Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4
timeFrame: 30 minutes after ACTH-challenge at Week 4
measure: Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8
timeFrame: 30 minutes after ACTH-challenge at Week 8
measure: Change in Albumin-corrected Serum Calcium From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Change in Albumin-corrected Serum Calcium From Baseline to Week 8
timeFrame: From baseline to Week 8
measure: Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment
timeFrame: From baseline to end of treatment
measure: Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8
timeFrame: From baseline to Week 8
measure: Change in 24-hour Urinary Calcium Excretion From Baseline to End of Treatment
timeFrame: From baseline to end of treatment
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: 8 weeks
measure: Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4
timeFrame: 30 and 60 minutes after ACTH-challenge at Week 4
measure: Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8
timeFrame: 30 and 60 minutes after ACTH-challenge at Week 8
measure: Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 8
timeFrame: From baseline to Week 8
measure: Change in Serum Alkaline Phosphatase From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Change in Serum Alkaline Phosphatase From Baseline to Week 8
timeFrame: From baseline to Week 8
measure: Pharmacokinetic Evaluation AUC(0-t)
timeFrame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
measure: Pharmacokinetic Evaluation AUC(0-infinity)
timeFrame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
measure: Pharmacokinetic Evaluation C(Max)
timeFrame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
measure: Pharmacokinetic Evaluation T(Max)
timeFrame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
measure: Pharmacokinetic Evaluation T(½)
timeFrame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
measure: Subjects With "Controlled Disease" According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment
timeFrame: End of treatment
measure: Percentage Change in PASI From Baseline to End of Treatment
timeFrame: From baseline to end of treatment
measure: Subjects With "Controlled Disease" According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment
timeFrame: End of treatment
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady's Children Hospital
state: California
city: Tampa
country: United States
facility: Clinical Research Center, Morsani Center for Advanced Healthcare
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Omaha
country: United States
facility: Skin Specialists, PC
state: Nebraska
city: Forest Hills
country: United States
facility: St. Luke's Roosevelt Hospital
state: New York
city: Johnston
country: United States
facility: Clinical Partners
state: Rhode Island
city: Charleston
country: United States
facility: Dermatology and Laser Center of Charleston, PA
state: South Carolina
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Winnipeg
country: Canada
facility: Winnipeg Clinic
state: Manitoba
city: St-John's
country: Canada
facility: Adult, Pediatric and Laser Derma
state: Newfoundland and Labrador
city: Markham
country: Canada
facility: Lynderm Research Inc.
state: Ontario
city: Peterborough
country: Canada
facility: Skin Centre for Dermatology
state: Ontario
city: Nice
country: France
facility: CHU de Nice
state: Alpe-Maritimes
city: Martigues
country: France
facility: Cabinet Medical
state: Bouches-du-Rhône
city: Quimper
country: France
facility: CHI de Cornouaille
state: Finistère
city: Berlin
country: Germany
facility: Charite Berlin
city: Bonn
country: Germany
facility: Uniklinik Bonn
city: Frankfurt am Main
country: Germany
facility: Uniklinik Frankfurt
city: Hamburg
country: Germany
facility: Katholisches Kinderkrankenhaus
city: Karczew
country: Poland
facility: Endo - Med. Centrum Medyczne Clinic
city: Lublin
country: Poland
facility: NZOZ Med.-Laser Clinic
city: Ostróda
country: Poland
facility: Specjalistyczny Ofrodek Leczniczo Clinic
city: Warszawa
country: Poland
facility: Medycyna Kliniczna Clinic
city: Wrocław
country: Poland
facility: Derm Medica Sp.zo.o. Clinic
city: Brasov
country: Romania
facility: Policlinica de Diagnostic Rapid S.A. Clinic
city: Bucharest
country: Romania
facility: Spitalul Clinic "Colentina"
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca
city: Galati
country: Romania
facility: Cabinet Medical Individual Tatu G. Alin Laurentiu
city: Iasi
country: Romania
facility: Iasiprest SRL Dermato-Venerology
city: Targu-Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Timisoara
country: Romania
facility: Spitalul Clinic Municipal de Urgenta Timisoara
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
state: Greater Manchester
city: Airdrie
country: United Kingdom
facility: Monklands Hospital
state: Lanarkshire
city: Leytonstone
country: United Kingdom
facility: Whipps Cross University Hospital
state: London
city: Stow Hill, Newport
country: United Kingdom
facility: St. Woolos Hospital
state: Monmouthshire
Study officials:
affiliation: Rady Chilidren's Hospital
name: Lawrence Eichenfield, MD
role: PRINCIPAL_INVESTIGATOR
References: