AAV Gene Therapy Screening/Observational Protocol (ECLIPSE) (ECLIPSE)

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorder; Haematologic Disease

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.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • The Alfred Hospital
  • Melbourne, Australia
    • Royal Children's Hospital, Parkville
  • Newcastle, Australia
    • Calvary Mater Hospital
  • Sydney, Australia
    • Royal Prince Alfred Hospital
  • Sydney, Australia
    • Westmead Hospital
• Austria
  • Vienna, Austria
    • Medical University of Vienna
• Canada
  • Hamilton, Canada
    • McMaster University Medical Centre
  • London, Canada
    • Lawson Health Research Institute
  • Moncton, Canada
    • The Moncton Hospital
  • Saskatoon, Canada
    • Saskatoon City Hospital
  • Winnipeg, Canada
    • University of Alberta Hospital
• France
  • Bron, France
    • Hôpital Louis Pradel - HCL
  • Paris, France
    • CHU Bicêtre
  • Paris, France
    • Hopital Necker-Enfants Malades - AP-HP
• Germany
  • Frankfurt, Germany
    • Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
  • Homburg, Germany
    • Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
• Ireland
  • Dublin, Ireland
    • St James Hospital
• Italy
  • Firenze, Italy
    • Azienda Ospedaliero-Universitaria Careggi
  • Genova, Italy
    • Istituto Giannina Gaslini
  • Milan, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Torino, Italy
    • Citta della Salute e della Scienza di Torino - Ospedale le Molinette
• Netherlands
  • Groningen, Netherlands
    • Groningen UMC
  • Rotterdam, Netherlands
    • Erasmus MC
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
• South Africa
  • Cape Town, South Africa
    • University of Cape Town Clinical Research Center
  • Johannesburg, South Africa
    • Charlotte Maxeke Johannesburg Academic Hospital
• Turkey
  • Istanbul, Turkey
    • Istanbul University Faculty of Medicine
  • Samsun, Turkey
    • Samsun Ondokuz Mayis University Medical Faculty
  • Seyhan, Turkey
    • Özel Acibadem Adana Hastanesi
  • İzmir, Turkey
    • Ege University Medical Faculty
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Cardiff, United Kingdom
    • Cardiff University Hospital
  • Glasgow, United Kingdom
    • Glasgow Royal Infirmary
  • London, United Kingdom
    • Royal Free London NHS Foundation Tust
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • St Thomas' Hospital
  • Manchester, United Kingdom
    • Manchester Royal Infirmary
  • Newcastle, United Kingdom
    • Newcastle Hemophilia Comprehensive Care Centre
  • Kent
    • Canterbury, Kent, United Kingdom
      • The Haemophilia and Thrombosis Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Sacramento, California, United States, 95817
      • University of California - Davis
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia and Thrombosis Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Buffalo, New York, United States, 14209
      • Hemophilia Center of Western New York
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina (UNC)
    • Greenville, North Carolina, United States, 27599
      • East Carolina University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Childrens Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Washington
    • Georgetown, Washington, United States, 20057
      • Lombardi Comprehensive Cancer Center at Georgetown University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Blood Center of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Haemophila B patients

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding episodes	Bleeding episode data recorded during the study	6 - 24 months
Factor IX replacement therapy consumption	Factor IX replacement therapy data recorded during the study	6 - 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To screen Haemophilia B patients for neutralising antibodies to a novel AAV vector (AAVS3).	AAV antibody assay result	6 - 24 months
To characterise baseline clinical parameters related to Haemophilia B.	Target joint data and health reasource utilisation	6 - 24 months

Collaborators and Investigators

• Sponsor: Freeline Therapeutics
• Investigators: Principal Investigator: Pratima Chowdary, Dr, The Royal Free Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Hemostatic Disorders; Hemophilia B; Blood Coagulation Disorders; Disease; Hematologic Diseases; Blood Coagulation Disorders, Inherited
• Other Study ID Numbers: FLT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No