Clinical trial NCT04272554: AAV Gene Therapy Screening/Observational Protocol (ECLIPSE)
Official title: Screening/Observational Protocol to Determine Patient Eligibility for Inclusion in AAV Gene Therapy Clinical Trials (ECLIPSE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorder
Haematologic Disease
Lead sponsor: Spur Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 37
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Haemophila B patients

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bleeding episodes
timeFrame: 6 - 24 months
measure: Factor IX replacement therapy consumption
timeFrame: 6 - 24 months
Secondary outcomes:
measure: To screen Haemophilia B patients for neutralising antibodies to a novel AAV vector (AAVS3).
timeFrame: 6 - 24 months
measure: To characterise baseline clinical parameters related to Haemophilia B.
timeFrame: 6 - 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California - Davis
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Hemophilia Center of Western New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina (UNC)
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Georgetown
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University
state: Washington
city: Milwaukee
country: United States
facility: Blood Center of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: Royal Children's Hospital, Parkville
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Newcastle
country: Australia
facility: Calvary Mater Hospital
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
city: Sydney
country: Australia
facility: Westmead Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
city: London
country: Canada
facility: Lawson Health Research Institute
city: Moncton
country: Canada
facility: The Moncton Hospital
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital
city: Winnipeg
country: Canada
facility: University of Alberta Hospital
city: Bron
country: France
facility: Hôpital Louis Pradel - HCL
city: Paris
country: France
facility: CHU Bicetre
city: Paris
country: France
facility: Hopital Necker-Enfants Malades - AP-HP
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes und Medizinische Fakultaet der Universitaet des Saarlandes
city: Dublin
country: Ireland
facility: St James Hospital
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Torino
country: Italy
facility: Citta della Salute e della Scienza di Torino - Ospedale le Molinette
city: Groningen
country: Netherlands
facility: Groningen UMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Cape Town
country: South Africa
facility: University of Cape Town Clinical Research Center
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Faculty of Medicine
city: İzmir
country: Turkey
facility: Ege University Medical Faculty
city: Samsun
country: Turkey
facility: Samsun Ondokuz Mayis University Medical Faculty
city: Seyhan
country: Turkey
facility: Özel Acibadem Adana Hastanesi
city: Canterbury
country: United Kingdom
facility: The Haemophilia and Thrombosis Centre
state: Kent
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cardiff
country: United Kingdom
facility: Cardiff University Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Tust
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Newcastle
country: United Kingdom
facility: Newcastle Hemophilia Comprehensive Care Centre
Study officials:
affiliation: The Royal Free Hospital
name: Pratima Chowdary, Dr
role: PRINCIPAL_INVESTIGATOR
References: