AAV Gene Therapy Screening/Observational Protocol (ECLIPSE)

Sponsor

Freeline Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04272554

Collaborator

(none)

200

Enrollment

Locations

77.5

Anticipated Duration (Months)

3.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

200 participants

Observational Model:

Case-Only

Time Perspective:

Other

Official Title:

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

Actual Study Start Date :

Feb 14, 2020

Anticipated Primary Completion Date :

Aug 1, 2026

Anticipated Study Completion Date :

Aug 1, 2026

Outcome Measures

Primary Outcome Measures

Bleeding episodes [6 - 24 months]
Bleeding episode data recorded during the study
Factor IX replacement therapy consumption [6 - 24 months]
Factor IX replacement therapy data recorded during the study

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria

Male participants, ≥ 16 years of age.
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.
Interested in participation in future gene therapy clinical studies.
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
Continuous routine FIX prophylaxis, OR
On demand FIX treatment
If receiving prophylaxis, participant has been on stable and adequate prophylaxis for at least 2 months prior to enrolment.

Exclusion Criteria:

Documented evidence of liver fibrosis and/ or liver dysfunction
Prior treatment with a gene transfer medicinal product.
Known presence or history of neutralising anti-human FIX antibodies (inhibitors)
Previously established serological evidence of HIV-1
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
Participants at high risk of thromboembolic events (history of arterial or venous thromboembolism
Known coagulation disorder other than Haemophilia B
Known history of an allergic reaction or anaphylaxis to Factor IX products or known uncontrolled allergic conditions
Known history of allergy to corticosteroids or to tacrolimus or any other macrolide
Known medical condition that would require chronic administration of corticosteroids (excluding topical formulations)
History of alcohol or drug dependence.
Planned surgical procedure within the next 12 months requiring prophylactic FIX treatment.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
2	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
3	University of California - Davis	Sacramento	California	United States	95817
4	University of South Florida	Tampa	Florida	United States	33612
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana	United States	46260
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
9	Hemophilia Center of Western New York	Buffalo	New York	United States	14209
10	University of North Carolina (UNC)	Chapel Hill	North Carolina	United States	27599
11	East Carolina University	Greenville	North Carolina	United States	27599
12	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
13	Nationwide Childrens Hospital	Columbus	Ohio	United States	43205
14	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
15	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
16	Lombardi Comprehensive Cancer Center at Georgetown University	Georgetown	Washington	United States	20057
17	Blood Center of Wisconsin	Milwaukee	Wisconsin	United States	53226
18	Royal Children's Hospital, Parkville	Melbourne		Australia
19	The Alfred Hospital	Melbourne		Australia
20	Calvary Mater Hospital	Newcastle		Australia
21	Royal Prince Alfred Hospital	Sydney		Australia
22	Westmead Hospital	Sydney		Australia
23	Medical University of Vienna	Vienna		Austria
24	McMaster University Medical Centre	Hamilton		Canada
25	Lawson Health Research Institute	London		Canada
26	The Moncton Hospital	Moncton		Canada
27	Saskatoon City Hospital	Saskatoon		Canada
28	University of Alberta Hospital	Winnipeg		Canada
29	Hôpital Louis Pradel - HCL	Bron		France
30	CHU Bicetre	Paris		France
31	Hopital Necker-Enfants Malades - AP-HP	Paris		France
32	Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet	Frankfurt		Germany
33	Universitaetsklinikum des Saarlandes und Medizinische Fakultaet der Universitaet des Saarlandes	Homburg		Germany
34	St James Hospital	Dublin		Ireland
35	Azienda Ospedaliero-Universitaria Careggi	Firenze		Italy
36	Istituto Giannina Gaslini	Genova		Italy
37	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milan		Italy
38	Citta della Salute e della Scienza di Torino - Ospedale le Molinette	Torino		Italy
39	Groningen UMC	Groningen		Netherlands
40	Erasmus MC	Rotterdam		Netherlands
41	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands
42	University of Cape Town Clinical Research Center	Cape Town		South Africa
43	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg		South Africa
44	Istanbul University Faculty of Medicine	Istanbul		Turkey
45	Ege University Medical Faculty	İzmir		Turkey
46	Samsun Ondokuz Mayis University Medical Faculty	Samsun		Turkey
47	Özel Acibadem Adana Hastanesi	Seyhan		Turkey
48	The Haemophilia and Thrombosis Centre	Canterbury	Kent	United Kingdom
49	Queen Elizabeth Hospital	Birmingham		United Kingdom
50	Cardiff University Hospital	Cardiff		United Kingdom
51	Glasgow Royal Infirmary	Glasgow		United Kingdom
52	Hammersmith Hospital	London		United Kingdom
53	Royal Free London NHS Foundation Tust	London		United Kingdom
54	St Thomas' Hospital	London		United Kingdom
55	Manchester Royal Infirmary	Manchester		United Kingdom
56	Newcastle Hemophilia Comprehensive Care Centre	Newcastle		United Kingdom