An International, Multi-centre, Prospective, Non-controlled, Open, Single-group, 8-week Trial in Adolescent Subjects

Psoriasis Vulgaris Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02038569
• Other study ID #: LP0076-1017
• Status: Completed
• Phase: Phase 2
• Start date: January 2014
• Est. completion date: February 13, 2018

Study information

• Verified date: October 2018
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: February 13, 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis
• Psoriasis Vulgaris

Intervention

Drug:
• LEO 80185 gel

Locations

Country	Name	City	State
Canada	Lynderm Research Inc.	Markham	Ontario
Canada	Skin Centre for Dermatology	Peterborough	Ontario
Canada	Adult, Pediatric and Laser Derma	St-John's	Newfoundland and Labrador
Canada	Winnipeg Clinic	Winnipeg	Manitoba
France	Cabinet Medical	Martigues	Bouches-du-Rhône
France	CHU de Nice	Nice	Alpe-Maritimes
France	CHI de Cornouaille	Quimper	Finistère
Germany	Charite Berlin	Berlin
Germany	Uniklinik Bonn	Bonn
Germany	Uniklinik Frankfurt	Frankfurt am Main
Germany	Katholisches Kinderkrankenhaus	Hamburg
Poland	Endo - Med. Centrum Medyczne Clinic	Karczew
Poland	NZOZ Med.-Laser Clinic	Lublin
Poland	Specjalistyczny Ofrodek Leczniczo Clinic	Ostróda
Poland	Medycyna Kliniczna Clinic	Warszawa
Poland	Derm Medica Sp.zo.o. Clinic	Wroclaw
Romania	Policlinica de Diagnostic Rapid S.A. Clinic	Brasov
Romania	Spitalul Clinic "Colentina"	Bucharest
Romania	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj-Napoca
Romania	Cabinet Medical Individual Tatu G. Alin Laurentiu	Galati
Romania	Iasiprest SRL Dermato-Venerology	Iasi
Romania	Spitalul Clinic Judetean Mures	Targu-Mures
Romania	Spitalul Clinic Municipal de Urgenta Timisoara	Timisoara
United Kingdom	Monklands Hospital	Airdrie	Lanarkshire
United Kingdom	Whipps Cross University Hospital	Leytonstone	London
United Kingdom	Manchester Royal Infirmary	Manchester	Greater Manchester
United Kingdom	St. Woolos Hospital	Stow Hill, Newport	Monmouthshire
United States	Dermatology and Laser Center of Charleston, PA	Charleston	South Carolina
United States	St. Luke's Roosevelt Hospital	Forest Hills	New York
United States	Indiana University	Indianapolis	Indiana
United States	Clinical Partners	Johnston	Rhode Island
United States	Skin Specialists, PC	Omaha	Nebraska
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Rady's Children Hospital	San Diego	California
United States	Clinical Research Center, Morsani Center for Advanced Healthcare	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Poland,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Drug Reactions (ADRs)	Number of Adverse Drug Reactions (ADRs)	8 weeks
Primary	Subjects With Serum Cortisol Concentration of =18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4	Number of subjects with serum cortisol concentration of =18 mcg/dl at 30 minutes after ACTH-challenge at Week 4	30 minutes after ACTH-challenge at Week 4
Primary	Subjects With Serum Cortisol Concentration of =18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8	Number of subjects with serum cortisol concentration of =18 mcg/dl at 30 minutes after ACTH-challenge at Week 8	30 minutes after ACTH-challenge at Week 8
Primary	Change in Albumin-corrected Serum Calcium From Baseline to Week 4	Change in albumin-corrected serum calcium from baseline to Week 4	From baseline to Week 4
Primary	Change in Albumin-corrected Serum Calcium From Baseline to Week 8	Change in albumin-corrected serum calcium from baseline to Week 8	From baseline to Week 8
Primary	Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment	Change in albumin-corrected serum calcium from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8.	From baseline to end of treatment
Primary	Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4	Change in 24-hour urinary calcium excretion from baseline to Week 4	From baseline to Week 4
Primary	Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8	Change in 24-hour urinary calcium excretion from baseline to Week 8	From baseline to Week 8
Primary	Change in 24-hour Urinary Calcium Excretion From Baseline to End of Treatment	Change in 24-hour urinary calcium excretion from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8.	From baseline to end of treatment
Secondary	Adverse Events (AEs)	Number of Adverse Events (AEs)	8 weeks
Secondary	Subjects With Serum Cortisol Concentration of =18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4	Number of subjects with serum cortisol concentration of =18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4	30 and 60 minutes after ACTH-challenge at Week 4
Secondary	Subjects With Serum Cortisol Concentration of =18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8	Number of subjects with serum cortisol concentration of =18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 8	30 and 60 minutes after ACTH-challenge at Week 8
Secondary	Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4	Change in urinary calcium:creatinine ratio from baseline to Week 4	From baseline to Week 4
Secondary	Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 8	Change in urinary calcium:creatinine ratio from baseline to Week 8	From baseline to Week 8
Secondary	Change in Serum Alkaline Phosphatase From Baseline to Week 4	Change in serum alkaline phosphatase from baseline to Week 4	From baseline to Week 4
Secondary	Change in Serum Alkaline Phosphatase From Baseline to Week 8	Change in serum alkaline phosphatase from baseline to Week 8	From baseline to Week 8
Secondary	Pharmacokinetic Evaluation AUC(0-t)	AUC(0-t) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-t) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-t). The mean value of AUC(0-t) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Secondary	Pharmacokinetic Evaluation AUC(0-infinity)	AUC(0-infinity) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-infinity) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-infinity). The mean value of AUC(0-infinity) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.; The terms AUC(0-infinity) and AUC(all) are interchangeable, AUC(0-infinity) was used in the protocol whereas AUC(all) was used in the report. AUC(0-infinity) has been used here to be consistent with the protocol.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Secondary	Pharmacokinetic Evaluation C(Max)	C(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore pharmacokinetic profiles could not be calculated. Presented C(max) values for betamethasone dipropionate and betamethasone 17-propionate are the the single highest concentrations measured in any sample at any time. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Secondary	Pharmacokinetic Evaluation T(Max)	T(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects. Therefore it was not possible to calculate T(max) for betamethasone dipropionate and betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Secondary	Pharmacokinetic Evaluation T(½)	T(½) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore it was not possible to calculate T(½) for betamethasone dipropionate or betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Secondary	Subjects With "Controlled Disease" According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment	Subjects with "Controlled disease" (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 investigator's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8.	End of treatment
Secondary	Percentage Change in PASI From Baseline to End of Treatment	Percentage change in Psoriasis area and severity index (PASI) score from baseline to end of treatment, defined as the last value recorded up to and including Week 8. Psoriasis area and severity index (PASI) assesses extent and severity of clinical signs of psoriasis vulgaris. Body surface is divided in 4 ares: head (incl. neck), arms (incl. hands), trunk (incl. flexures) and legs (incl. buttocks and feet). Each area is scored from 0-6 for extent of psoriasis and from 0-4 for redness, thickness, and scaliness, and an area PASI score is calculated. The total PASI score is calculated from each area's score. The PASI score ranges from 0 (clear skin) to 72 (maximum disease), a PASI score higher than 10 generally corresponds to moderate-to-severe disease.	From baseline to end of treatment
Secondary	Subjects With "Controlled Disease" According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment	Subjects with "Controlled disease" (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 patient's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8.	End of treatment