Clinical trial NCT03068780: Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa
Official title: Double-blind, Randomised, Vehicle-controlled, Phase III, Efficacy and Safety Study With 24-month Open-label Follow-up of Oleogel-S10 in Patients With Inherited Epidermolysis Bullosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epidermolysis Bullosa
Lead sponsor: Amryt Pharma
Sponsor class: INDUSTRY
First posted: 2017-03-03
Enrollment: 223
Sex: ALL
Minimum age (years): 21
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a Phase III, Efficacy and Safety Study of Oleogel-S10 in Participants with Inherited Epidermolysis Bullosa (EB).

EB is a rare group of genetic skin fragility disorders characterised by blistering of the skin in response to minor injury. In most cases, onset of EB is at birth or shortly after. All participants affected by any type of EB share the main characteristic of repeatedly developing painful wounds that take days to months to heal. Current treatment of EB is primarily preventative and supportive including protection from mechanical forces by avoiding rubbing, early treatment of wounds to prevent infections, and protection of the wound with adequate non-adhesive dressings to enable healing.

The active pharmaceutical ingredient in Oleogel-S10 is a refined birch bark extract, quantified to 72 to 88% betulin.

This clinical study of Oleogel-S10 in patients with inherited EB has been carried out to investigate whether Oleogel-S10 is effective for treatment of EB wounds and safe for long-term use.

Oleogel-S10 was compared to a control gel. The control gel matched Oleogel-S10 in terms of texture and visual appearance to allow for double-blinding. The packaging for Oleogel-S10 gel and the control gel were identical. The participant received either Oleogel-S10 or control gel for a double-blind study phase of 90 days. The probability that the participant received Oleogel-S10 was 50%, which means that they had a 1 in 2 chance of receiving Oleogel-S10. However, in the follow-up phase of the study all participants were treated with Oleogel-S10 for a period of 24 months.

This clinical study was performed at 49 study sites in 26 countries (Argentina, Australia, Austria, Brazil, Chile, Colombia, Czech Republic, Denmark, France, Georgia, Germany, Greece, Hong Kong \[China\], Hungary, Ireland, Israel, Italy, Romania, Russia, Serbia, Singapore, Spain, Switzerland, Ukraine, United Kingdom, and the United States); 223 participants participated in total.


Eligibility criteria: Inclusion Criteria:

* Male and female patients with the following subtypes of inherited EB: junctional EB (JEB), dystrophic EB (DEB), and Kindler EB aged ≥21 days
* Patients with an EB target wound (i.e., EB partial thickness wound of 10 cm² to 50 cm² in size aged ≥21 days and \<9 months)
* Patient and/or his/her legal representative has/have been informed, has/have read and understood the patient information/informed consent form, and has/have given written informed consent
* Patient and/or his/her legal representative must be able and willing to follow study procedures and instructions

Exclusion Criteria:

* Patient has EB simplex
* EB target wound that is ≥9 months old or has clinical signs of local infection
* Use of systemic antibiotics for wound-related infections within 7 days prior to enrolment
* Administration of systemic or topical steroids (except for inhaled, ophthalmic or topical applications, such as budesonide suspension for oesophageal strictures \[e.g., Pulmicort respules® 0.25 mg/2 mL or 0.5 mg/2 mL\]) within 30 days before enrolment
* Immunosuppressive therapy or cytotoxic chemotherapy within 60 days prior to enrolment
* Patient has undergone stem cell transplant or gene therapy for the treatment of inherited EB
* Current and/or former malignancy including basal cell carcinomas and squamous cell carcinomas
* Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry
* Factors present in the patient and/or his/her legal representative that could interfere with study compliance such as inability to attend scheduled study visits or compliance with home dressing changes
* Pregnant or nursing women and women of childbearing potential including postmenarchal female adolescents not willing to use an effective form of birth control with failure rates \<1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine contraceptive device, sexual abstinence, vasectomised partner) during participation in the study (and at least 3 months thereafter)
* Patient is a member of the investigational team or his/her immediate family
* Patient lives in the same household as a study participant

Primary outcomes:
measure: Proportion of Patients With First Complete Closure of the EB Target Wound Within 45 Days of Treatment
timeFrame: 45±7 days
Secondary outcomes:
measure: Time to First Complete Closure of the EB Target Wound as Evidenced by Clinical Assessment Until Day 90 (D90) or End of Double-blind Phase (EDBP)
timeFrame: 90±7 days
measure: Proportion of Patients With First Complete Closure of the EB Target Wound at D90 or EDBP Based on Clinical Assessment by the Investigator Until D90 or EDBP
timeFrame: 90±7 days
measure: The Incidence of EB Target Wound Infection Between Baseline (DBP D0) and D90 or EDBP as Evidenced by Adverse Events (AEs) and/or Use of Topical and/or Systemic Antibiotics (Related to Wound Infection)
timeFrame: 90±7 days
measure: The Maximum Severity of EB Target Wound Infection Between Baseline (DBP D0) and D90 or EDBP as Evidenced by AEs
timeFrame: 90±7 days
measure: Change From Baseline (DBP D0) in Total Body Wound Burden as Evidenced by Clinical Assessment Using Section I (Assessment of the Skin Except for the Anogenital Region) of the 'EB Disease Activity and Scarring Index' (EBDASI), at D90 or EDBP
timeFrame: 90±7 days
measure: Change From Baseline (DBP D0) in Itching Using the 'Itch Man Scale' in Patients ≥ 4 Years and up to 13 Years of Age Before Wound Dressing Changes at D90 or EDBP
timeFrame: 90±7 days
measure: Change From Baseline (DBP D0) in Itching Using the 'Leuven Itch Scale' in Patients ≥ 14 Years of Age Before Wound Dressing Changes at D90 or End of Double Blind Phase (EDBP)
timeFrame: 90±7 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Amjad Plastic Research
state: Florida
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: Buenos Aires
country: Argentina
facility: Consutorios Medicos (Instituto de Neumonologia y Dermatologia)
city: Buenos Aires
country: Argentina
facility: Centro Médico Dra. De Salvo
city: Buenos Aires
country: Argentina
facility: Centro de investigaciones Metabolicas, CINME
city: Sydney
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Premier Specialists
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Parkville
country: Australia
facility: Murdoch Childrens Research Institute Royal Children's Hospital
state: Victoria
city: Salzburg
country: Austria
facility: Universitaetsklinik fuer Dermatologie
city: Recife
country: Brazil
facility: IMIP
state: Pernanbuco
city: Blumenau
country: Brazil
facility: Universidade Regional de Blumenau
state: Santa Catarina
city: São Paulo
country: Brazil
facility: Instituto Da Crianca HCFMUSP
city: Santiago
country: Chile
facility: Fundacion Debra Chile
city: Bogotá
country: Colombia
facility: Hospital De San Jose
state: DC
city: Brno
country: Czechia
facility: University Hospital Brno, Children´s Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Toulouse
country: France
facility: CHU Toulouse - Hospital Larrey
city: Tbilisi
country: Georgia
facility: S/R National Center of Dermatology and Venerology
city: Freiburg im Breisgau
country: Germany
facility: Medical Center University Freiburg
city: Hannover
country: Germany
facility: Kinder- und Jugendkrankenhaus AUF DER BULT
city: Athens
country: Greece
facility: Hospital of Skin and Veneral Diseases "A. Syggros"
state: Attiki
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital, The Chinese University of Hong Kong
city: Budapest
country: Hungary
facility: Semmelweis University, Faculty of Medicine
city: Dublin
country: Ireland
facility: Our Ladys Childrens Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Bambino Gesù Children Hospital
city: Roma
country: Italy
facility: Istituto Dermopatico dell'Immacolata IDI-IRCCS
city: Bucharest
country: Romania
facility: Centrul Medical Sanador
city: Moscow
country: Russian Federation
facility: State Scientific Center for Dermatovenerology and Cosmetology
city: Moscow
country: Russian Federation
facility: Scientific Center of Children's Health
city: Belgrade
country: Serbia
facility: University of Belgrade, School of Medicine
city: Singapore
country: Singapore
facility: Kandang Kerbau (KK) Women's and Children's Hospital
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Barcelona
country: Spain
facility: Hospital Universitari de la Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Viamed Santa Ángela de la Cruz
city: Bern
country: Switzerland
facility: Bern University Hospital
city: Kyiv
country: Ukraine
facility: National Children Specialized Hospital "Ohmatdyt" of Ministry of Health of Ukraine
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street hospital
Study officials:
affiliation: Melbourne Health
name: Johannes S Kern, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: