Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa

NCT03068780 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: BEB-132016-002066-32
• Study Type: interventional
• Target: 223
• Locations: 25 countries
• Sites: 47

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.

Conditions

Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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)

  90±7 days

• 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

  90±7 days

• 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)

  90±7 days

• The Maximum Severity of EB Target Wound Infection Between Baseline (DBP D0) and D90 or EDBP as Evidenced by AEs

  90±7 days

• 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

  90±7 days

Study Arms (2)

Oleogel-S10

EXPERIMENTAL

Drug: Oleogel-S10

Control Gel

PLACEBO COMPARATOR

Drug: Control gel

Interventions

Oleogel-S10 DRUG

10% birch bark extract in 90% sunflower oil

Also known as: Episalvan, Filsuvez

Oleogel-S10

Control gel DRUG

Sunflower oil, Cera flava/yellow wax, and Carnauba wax (matched Oleogel-S10 in terms of texture and visual appearance)

Also known as: Vehicle gel

Control Gel

Eligibility Criteria

• Age: 21 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amryt Research Limited: lead

Study Sites (51)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Amjad Plastic Research

Miami, Florida, 33144, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11790, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

Consutorios Medicos (Instituto de Neumonologia y Dermatologia)

Buenos Aires, 1425, Argentina

Location

Centro Médico Dra. De Salvo

Buenos Aires, 1426, Argentina

Location

Centro de investigaciones Metabolicas, CINME

Buenos Aires, C1056ABJ, Argentina

Location

Sydney Children's Hospital

Sydney, New South Wales, 2031, Australia

Location

Premier Specialists

Sydney, New South Wales, 2217, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Murdoch Childrens Research Institute Royal Children's Hospital

Parkville, Victoria, 3502, Australia

Location

Universitaetsklinik fuer Dermatologie

Salzburg, 5020, Austria

Location

IMIP

Recife, Pernanbuco, 50070550, Brazil

Location

Universidade Regional de Blumenau

Blumenau, Santa Catarina, 89020400, Brazil

Location

Instituto Da Crianca HCFMUSP

São Paulo, 05403.000, Brazil

Location

Fundacion Debra Chile

Santiago, 7760099, Chile

Location

Hospital De San Jose

Bogotá, DC, Colombia

Location

University Hospital Brno, Children´s Hospital

Brno, 61500, Czechia

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

CHU Toulouse - Hospital Larrey

Toulouse, 31059, France

Location

S/R National Center of Dermatology and Venerology

Tbilisi, 159, Georgia

Location

Medical Center University Freiburg

Freiburg im Breisgau, 79104, Germany

Location

Kinder- und Jugendkrankenhaus AUF DER BULT

Hanover, 30173, Germany

Location

Hospital of Skin and Veneral Diseases "A. Syggros"

Athens, Attica, 16121, Greece

Location

Prince of Wales Hospital, The Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

Semmelweis University, Faculty of Medicine

Budapest, 1085, Hungary

Location

Our Ladys Childrens Hospital

Dublin, Ireland

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Bambino Gesù Children Hospital

Roma, 00165, Italy

Location

Istituto Dermopatico dell'Immacolata IDI-IRCCS

Roma, 00167, Italy

Location

Centrul Medical Sanador

Bucharest, 011025, Romania

Location

State Scientific Center for Dermatovenerology and Cosmetology

Moscow, 107076, Russia

Location

Scientific Center of Children's Health

Moscow, 119991, Russia

Location

University of Belgrade, School of Medicine

Belgrade, 11000, Serbia

Location

Kandang Kerbau (KK) Women's and Children's Hospital

Singapore, 229899, Singapore

Location

Hospital Sant Joan de Déu

Barcelona, 08950, Spain

Location

Hospital Universitari de la Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Viamed Santa Ángela de la Cruz

Seville, 41014, Spain

Location

Bern University Hospital

Bern, 3010, Switzerland

Location

National Children Specialized Hospital "Ohmatdyt" of Ministry of Health of Ukraine

Kyiv, 01135, Ukraine

Location

Birmingham Children's Hospital NHS Trust

Birmingham, United Kingdom

Location

Great Ormond Street hospital

London, WC1N3JH, United Kingdom

Location

Related Publications (1)

• Kern JS, Schwieger-Briel A, Lowe S, Sumeray M, Davis C, Martinez AE. Oleogel-S10 Phase 3 study "EASE" for epidermolysis bullosa: study design and rationale. Trials. 2019 Jun 11;20(1):350. doi: 10.1186/s13063-019-3362-z.

  PMID: 31186047 DERIVED

MeSH Terms

Conditions

Epidermolysis Bullosa

Interventions

episalvan

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Results Point of Contact

• Title: Janet Boylan
• Organization: Amryt Research Limited

Janet.boylan@amrytpharma.com

+3531518

Study Officials

• Johannes S Kern, MD PhD

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 3, 2017
• Study Start: March 29, 2017
• Primary Completion: June 11, 2020
• Study Completion: May 27, 2022
• Last Updated: July 20, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DK (1); HK (1); CH (1); FR (2); UA (1); US (10); GR (1); AU (1); GE (1); BR (3); DE (2); CO (1); HU (1); IE (1); IL (1); AR (3); RO (1); RU (2); SG (1); IT (3); ES (4); GB (2); CZ (1); CL (1)