AAV Gene Therapy Screening/Observational Protocol (ECLIPSE)

Hemophilia B Clinical Trial

— ECLIPSE  

Official title:

Screening/Observational Protocol to Determine Patient Eligibility for Inclusion in AAV Gene Therapy Clinical Trials (ECLIPSE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04272554
• Other study ID #: FLT-01
• Status: Completed
• Start date: February 14, 2020
• Est. completion date: October 10, 2022

Study information

• Verified date: November 2022
• Source: Freeline Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Freeline is developing adeno-associated virus (AAV) vector based gene therapies for a number of diseases and is actively advancing a programme in Haemophilia B (HB). This study aims to collect prospective data to characterise bleeding events and Factor IX (FIX) concentrate consumption in HB patients that can be used as baseline for participants who elect to participate in a subsequent Freeline gene therapy study. The study will also screen participants for antibodies to a novel AAV vector to assess their suitability for inclusion in a Freeline gene therapy treatment study.

Description:

This is a prospective study to collect baseline disease characteristics in patients with HB that are required to establish eligibility for treatment with a novel AAV gene therapy in a subsequent Freeline gene therapy treatment study.

Participants providing consent will attend an enrolment visit to complete eligibility evaluations, collect health and demographic information and receive instruction for completing the study diary. Participants will then complete a diary recording bleeding episodes and FIX usage until they enrol into a gene therapy treatment study. A blood sample will be drawn at a convenient timepoint during the study to assess the participant's AAV neutralising antibody (NAb) status.

No treatment intervention will occur as part of this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: October 10, 2022
• Est. primary completion date: October 10, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years and older

Eligibility

Inclusion Criteria

1. Male participants, = 16 years of age.

2. Able to give full informed consent or obtain full informed consent/assent (according to local regulations) and/or obtain full informed consent from the participant's legally acceptable representative (as appropriate), and able to understand and comply with all requirements of the study, including diary completion.

3. Interested in participation in future gene therapy clinical studies.

4. Subjects with Haemophilia B with known severe or moderately severe FIX deficiency (=2% of normal circulating FIX activity) for which the subject is either on

1. Continuous routine FIX prophylaxis, OR

2. On demand FIX treatment

5. If receiving prophylaxis, participant has been on stable and adequate prophylaxis for at least 2 months prior to enrolment.

Exclusion Criteria:

1. Documented evidence of liver fibrosis and/ or liver dysfunction

2. Prior treatment with a gene transfer medicinal product.

3. Known presence or history of neutralising anti-human FIX antibodies (inhibitors)

4. Previously established serological evidence of HIV-1

5. Documented active hepatitis B or C, and HBsAg or HCV RNA viral load positivity, respectively, or currently on antiviral therapy for hepatitis B or C

6. Participants at high risk of thromboembolic events (history of arterial or venous thromboembolism

7. Known coagulation disorder other than Haemophilia B

8. Known history of an allergic reaction or anaphylaxis to Factor IX products or known uncontrolled allergic conditions

9. Known history of allergy to corticosteroids or to tacrolimus or any other macrolide

10. Known medical condition that would require chronic administration of corticosteroids (excluding topical formulations)

11. History of alcohol or drug dependence.

12. Planned surgical procedure within the next 12 months requiring prophylactic FIX treatment.

13. Known active severe infection (including documented COVID-19 infection), or any other significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with adherence to the protocol procedures or with tolerance to gene therapy in a future treatment study including, but not limited to, renal, hepatic, cardiovascular, opthalmological, hematological, immunological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, malignancy or any other psychological disorder.

Related Conditions & MeSH terms

• Blood Coagulation Disorder
• Blood Coagulation Disorders
• Blood Coagulation Disorders, Inherited
• Disease
• Haematologic Disease
• Hematologic Diseases
• Hemophilia B
• Hemostatic Disorders

Locations

Country	Name	City	State
Australia	Royal Children's Hospital, Parkville	Melbourne
Australia	The Alfred Hospital	Melbourne
Australia	Calvary Mater Hospital	Newcastle
Australia	Royal Prince Alfred Hospital	Sydney
Australia	Westmead Hospital	Sydney
Austria	Medical University of Vienna	Vienna
Canada	McMaster University Medical Centre	Hamilton
Canada	Lawson Health Research Institute	London
Canada	The Moncton Hospital	Moncton
Canada	Saskatoon City Hospital	Saskatoon
Canada	University of Alberta Hospital	Winnipeg
France	Hôpital Louis Pradel - HCL	Bron
France	CHU Bicetre	Paris
France	Hopital Necker-Enfants Malades - AP-HP	Paris
Germany	Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet	Frankfurt
Germany	Universitaetsklinikum des Saarlandes und Medizinische Fakultaet der Universitaet des Saarlandes	Homburg
Ireland	St James Hospital	Dublin
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Istituto Giannina Gaslini	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milan
Italy	Citta della Salute e della Scienza di Torino - Ospedale le Molinette	Torino
Netherlands	Groningen UMC	Groningen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
South Africa	University of Cape Town Clinical Research Center	Cape Town
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg
Turkey	Istanbul University Faculty of Medicine	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Samsun Ondokuz Mayis University Medical Faculty	Samsun
Turkey	Özel Acibadem Adana Hastanesi	Seyhan
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	The Haemophilia and Thrombosis Centre	Canterbury	Kent
United Kingdom	Cardiff University Hospital	Cardiff
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free London NHS Foundation Tust	London
United Kingdom	St Thomas' Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Newcastle Hemophilia Comprehensive Care Centre	Newcastle
United States	University of Michigan	Ann Arbor	Michigan
United States	Hemophilia Center of Western New York	Buffalo	New York
United States	University of North Carolina (UNC)	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	Lombardi Comprehensive Cancer Center at Georgetown University	Georgetown	Washington
United States	East Carolina University	Greenville	North Carolina
United States	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Blood Center of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	University of California - Davis	Sacramento	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Freeline Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Ireland,  Italy,  Netherlands,  South Africa,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bleeding episodes	Bleeding episode data recorded during the study	6 - 24 months
Primary	Factor IX replacement therapy consumption	Factor IX replacement therapy data recorded during the study	6 - 24 months
Secondary	To screen Haemophilia B patients for neutralising antibodies to a novel AAV vector (AAVS3).	AAV antibody assay result	6 - 24 months
Secondary	To characterise baseline clinical parameters related to Haemophilia B.	Target joint data and health reasource utilisation	6 - 24 months