Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03068780
Other study ID # BEB-13
Secondary ID 2016-002066-32
Status Completed
Phase Phase 3
First received
Last updated
Start date March 29, 2017
Est. completion date May 27, 2022

Study information

Verified date July 2023
Source Amryt Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 223
Est. completion date May 27, 2022
Est. primary completion date June 11, 2020
Accepts healthy volunteers No
Gender All
Age group 21 Days and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Oleogel-S10
10% birch bark extract in 90% sunflower oil
Control gel
Sunflower oil, Cera flava/yellow wax, and Carnauba wax (matched Oleogel-S10 in terms of texture and visual appearance)

Locations

Country Name City State
Argentina Centro de investigaciones Metabolicas, CINME Buenos Aires
Argentina Centro Médico Dra. De Salvo Buenos Aires
Argentina Consutorios Medicos (Instituto de Neumonologia y Dermatologia) Buenos Aires
Australia Murdoch Childrens Research Institute Royal Children's Hospital Parkville Victoria
Australia The Royal Melbourne Hospital Parkville Victoria
Australia Premier Specialists Sydney New South Wales
Australia Sydney Children's Hospital Sydney New South Wales
Austria Universitaetsklinik fuer Dermatologie Salzburg
Brazil Universidade Regional de Blumenau Blumenau Santa Catarina
Brazil IMIP Recife Pernanbuco
Brazil Instituto Da Crianca HCFMUSP São Paulo
Chile Fundacion Debra Chile Santiago
Colombia Hospital De San Jose Bogotá DC
Czechia University Hospital Brno, Children´s Hospital Brno
Denmark Aarhus University Hospital Aarhus
France Hôpital Necker-Enfants Malades Paris
France CHU Toulouse - Hospital Larrey Toulouse
Georgia S/R National Center of Dermatology and Venerology Tbilisi
Germany Medical Center University Freiburg Freiburg im Breisgau
Germany Kinder- und Jugendkrankenhaus AUF DER BULT Hannover
Greece Hospital of Skin and Veneral Diseases "A. Syggros" Athens Attiki
Hong Kong Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong
Hungary Semmelweis University, Faculty of Medicine Budapest
Ireland Our Ladys Childrens Hospital Dublin
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan
Italy Bambino Gesù Children Hospital Roma
Italy Istituto Dermopatico dell'Immacolata IDI-IRCCS Roma
Romania Centrul Medical Sanador Bucharest
Russian Federation Scientific Center of Children's Health Moscow
Russian Federation State Scientific Center for Dermatovenerology and Cosmetology Moscow
Serbia University of Belgrade, School of Medicine Belgrade
Singapore Kandang Kerbau (KK) Women's and Children's Hospital Singapore
Spain Hospital Sant Joan de Déu Barcelona
Spain Hospital Universitari de la Vall d'Hebron Barcelona
Spain Hospital Universitario La Paz Madrid
Spain Hospital Viamed Santa Ángela de la Cruz Sevilla
Switzerland Bern University Hospital Bern
Ukraine National Children Specialized Hospital "Ohmatdyt" of Ministry of Health of Ukraine Kyiv
United Kingdom Birmingham Children's Hospital NHS Trust Birmingham
United Kingdom Great Ormond Street hospital London
United States Children's Hospital Colorado Aurora Colorado
United States Medical University of South Carolina Charleston South Carolina
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Amjad Plastic Research Miami Florida
United States University of Minnesota Minneapolis Minnesota
United States The Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Texas Dermatology and Laser Specialists San Antonio Texas
United States Stony Brook University Hospital Stony Brook New York

Sponsors (1)

Lead Sponsor Collaborator
Amryt Research Limited

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Chile,  Colombia,  Czechia,  Denmark,  France,  Georgia,  Germany,  Greece,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Romania,  Russian Federation,  Serbia,  Singapore,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of Patients With First Complete Closure of the EB Target Wound Within 45 Days of Treatment Proportion of subjects with first complete closure of the EB target wound (defined as EB partial-thickness wound of 10 cm2 to 50 cm2 in size and =21 days to <9 months in age) in subjects with inherited EB (subtypes DEB, JEB, or Kindler EB) within 45 days of treatment with Oleogel-S10 compared to control gel based on clinical assessment by the investigator (the wound was rated as "closed" at first appearance of complete re-epithelialization without drainage). 45±7 days
Secondary 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) The first key secondary endpoint was time to first complete closure of the EB target wound as evidenced by clinical assessment within 90 days or by EDBP, using a nonstratified log-rank test.
If the primary analysis of the primary efficacy endpoint showed superiority at the 5% significance level, hierarchical confirmatory testing of the 6 key secondary endpoints was to be performed.
90±7 days
Secondary 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 The second key secondary endpoint was the proportion of subjects with first complete closure of the EB target wound within 90 days of treatment or by EDBP based on clinical assessment by the investigator. 90±7 days
Secondary 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) The incidence of EB target wound infections between Baseline (DBP D0) and D90 or EDBP was assessed based on the total number of patients with an EB target wound infection, as evidenced by AEs and/or the use of topical and/or systemic antibiotics, and the total number of patients 90±7 days
Secondary The Maximum Severity of EB Target Wound Infection Between Baseline (DBP D0) and D90 or EDBP as Evidenced by AEs Target wound infections between baseline (DBP D0) and D90 or EDBP were assessed for maximum severity (maximum severity was evaluated if a subject had a wound infection event evidenced by AEs). [Note: Here, 1 event less is recorded in the control gel group as for the previous secondary outcome measure, because only wound infections that were reported as AEs could be assessed for severity and were included in this analysis.] 90±7 days
Secondary 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 The evaluation of total body wound burden (TBWB) was based on clinical assessment using Section I (Skin) of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). The EBDASI skin activity (blistering/erosions/crusting) was scored from 0 to 10 for each of 10 anatomical locations (excluding the anogenital and buttocks regions). Therefore, the total skin activity score (i.e., TBWB) could range from 0 to 100, with lower scores indicative of less wound burden. The change in TBWB was assessed from baseline (DBP D0) to D90 or EDBP. 90±7 days
Secondary 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 Change from Baseline at D90 or EDBP on the Itch Man Scale in patients 4-13 years of age. The scale runs from 0 (comfortable, no itch) to 4 (itches most terribly, impossible to sit still, concentrate). 90±7 days
Secondary 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) Change in Leuven Itch Scale (patients = 14 years of age) scores taken from two time points, Baseline and Day 90±7 [End of Double Blind Phase (EDBP)]. The Leuven Itch Scale measures six dimensions of the itch experience: Frequency Subscore (0 = Never to 100 = Always); Duration Subscore (0 = Between 0 and 30 minutes to 100 = More than 2 hours); Severity Subscore (0 = No itch to 100 = Worst possible itch); Consequences Subscore [0 = Never to 100 = Always (lower score indicates less negative consequences from the itch)]; Distress Subscore (0 = Not distressing at all to 100 = Very distressing); Surface Area Subscore (0-100, high values indicate more parts of the body are itching) 90±7 days
See also
  Status Clinical Trial Phase
Completed NCT00380640 - The Efficacy of Trimethoprim in Wound Healing of Patients With Epidermolysis Bullosa Phase 2
Completed NCT00004761 - Establishment of the National Epidermolysis Bullosa Registry N/A
Completed NCT01263379 - Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa Phase 1/Phase 2
Completed NCT01716169 - Treatment of Chronic and Non-Chronic Wounds in Patients With Recessive Dystrophic Epidermolysis Bullosa Using Helicoll Collagen Dressings Versus Standard of Care N/A
Withdrawn NCT01454687 - Grafting of Epidermolysis Bullosa Wounds Using Cultured Revertant Autologous Keratinocytes N/A
Completed NCT00014729 - Phase I Study of Isotretinoin in Patients With Recessive Dystrophic Epidermolysis Bullosa Phase 1
Recruiting NCT05838092 - Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of Epidermolysis Bullosa (Phase III) Phase 3
Recruiting NCT03269474 - Computational Drug Repurposing for All EBS Cases
Terminated NCT02090283 - Open-Label Extension Study to Evaluate the Safety of SD-101 Cream in Participants With Epidermolysis Bullosa Phase 2
Completed NCT02582775 - MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs Phase 2
Recruiting NCT04213703 - A Pilot Study to Explore the Role of Gut Flora in Epidermolysis Bullosa
Completed NCT02384460 - ESSENCE Study: Efficacy and Safety of SD-101 Cream in Participants With Epidermolysis Bullosa Phase 3
Terminated NCT02670330 - Open Label Extension Study to Evaluate the Long-term Safety of Zorblisa (SD-101-6.0) in Patients With Epidermolysis Bullosa Phase 3
Terminated NCT01619670 - A Observational Study to Evaluate Apligraf(R) in Nonhealing Wounds of Subjects With Epidermolysis Bullosa Phase 4
Recruiting NCT01340235 - Treatment of Dowling Maera Type of Epidermolysis Bullosa Simplex by Oral Erythromycin Phase 3
Completed NCT02014376 - Study of Effectiveness and Safety of SD-101 in Participants With Epidermolysis Bullosa Phase 2
Completed NCT04217538 - Observational Study of a Cohort of Patients With Hereditary Epidermolysis Bullosa
Completed NCT03942250 - Uses of Irradiated Human Amniotic Membrane in the Treatment of Dystrophic Epidermolysis Bullosa Patients N/A
Completed NCT01033552 - Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs Phase 1/Phase 2
Completed NCT04227106 - Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) Phase 3