Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Haemophilia B Patients Who Have Undergone Gene Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03641703
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Freeline Therapeutics

Brief Summary:

Severe haemophilia B (HB) is a bleeding disorder where a protein made by the body to help make blood clot is either partly or completely missing. This protein is called a clotting factor; with severe HB, levels of clotting Factor IX (nine; FIX) are very low and affected individuals can suffer life threatening bleeding episodes. HB mainly affects boys and men (approximately one in every 30,000 males). Current treatment for HB involves intravenous infusions of FIX as regular treatment (prophylaxis) or 'on demand' treatment. On demand treatment is highly effective at stopping bleeding but cannot fully reverse long-term damage that follows after a bleed. Regular treatment can prevent bleeding; however it is invasive for patients and also expensive.

This clinical study aims to investigate the long-term safety and durability of FIX activity in participants who have been dosed with a new gene therapy product (FLT180a) in earlier clinical studies. Following administration, FLT180a results in production of FIX in the participants liver cells which is then released into the blood stream. The aim is to have the participants own body produce levels of FIX that allow for clotting to occur as normal as would be seen in a non-HB individual. This would remove the need for prophylaxis or on demand treatment following just a single administration of FLT180a.

Up to 50 participants who have already been administered with FLT180a in the EU and US will take part in this study. Participants will be followed up in this trial until they have reached 15 years post gene transfer. Participants will undergo procedures including physical examinations, blood tests and liver ultrasounds. Participants will also need to complete a diary to document occurrence of bleeding episodes and record the amount of Factor IX concentrate they receive. Patient reports outcomes including measures of Quality of Life, disability and physical activity will also be collected.


Condition or disease Intervention/treatment Phase
Hemophilia B Biological: FLT180a Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicentre, Long-Term Follow-Up Study to Investigate the Safety and Durability of Response Following Dosing of a Novel Adeno-Associated Viral Vector (FLT180a) in Patients With Haemophilia B
Actual Study Start Date : July 10, 2018
Estimated Primary Completion Date : December 2035
Estimated Study Completion Date : December 2035

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FLT180a
Participants receiving gene therapy vector
Biological: FLT180a
FLT180a is a replication-incompetent adeno- associated viral vector. The vector is composed of a DNA vector genome encapsidated in an adeno-associated virus derived protein capsid. The expression cassette contains DNA encoding Factor IX.




Primary Outcome Measures :
  1. Frequency of treatment-emergent adverse events/reactions (AE/ARs) reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Primary Safety). [ Time Frame: From entry to 15 years post dosing ]
  2. Change from baseline (prior to FLT180a dosing) in hFIX activity as a percentage change of normal values at each visit (Primary Efficacy). [ Time Frame: From entry to 5 years post dosing ]

Secondary Outcome Measures :
  1. The proportion of patients achieving hFIX activity at or above 5%, 15% and 40% of normal. [ Time Frame: From entry to 5 years post dosing ]
  2. Change from baseline (prior to FLT180a dosing) in annualised bleeding rate by measurement of number of breakthrough bleeding episodes. [ Time Frame: From entry to 5 years post dosing ]
  3. Change from baseline (prior to FLT180a dosing) in FIX concentrate consumption by measurement of factor concentrate consumed by the patient. [ Time Frame: From entry to 5 years post dosing ]
  4. FLT180a effectiveness related to surgical/dental procedures by assessment of consumption of exogenous clotting factors at Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery. [ Time Frame: From entry to 5 years post dosing ]
    Consumption of exogenous clotting factors, related to an individual surgery, will be collected at the three time-points (Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery) for each surgery occurring from patient entry into trial until 5 years post-dosing.

  5. FLT180a effectiveness related to surgical/dental procedures by assessment of measurement of absolute blood loss at Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery. [ Time Frame: From entry to 5 years post dosing ]
    Measurement of absolute blood loss, related to an individual surgery, will be collected at the three time-points (Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery) for each surgery occurring from patient entry into trial until 5 years post-dosing.

  6. FLT180a effectiveness related to surgical/dental procedures by assessment of blood transfusion requirement, volume and number of transfusions at Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery. [ Time Frame: From entry to 5 years post dosing ]
    Transfusion requirement (volume and number of transfusions), related to an individual surgery, will be collected at the three time-points (Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery) for each surgery occurring from patient entry into trial until 5 years post-dosing.

  7. FLT180a effectiveness related to surgical/dental procedures by assessment of efficacy of haemostasis as judged by surgeon on a 4-point scale at Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery. [ Time Frame: From entry to 5 years post dosing ]
    Assessment of efficacy of haemostasis as judged by surgeon, related to an individual surgery, will be collected at the three time-points (Time of surgery, Time of drain removal (if applicable) and The earlier of discharge of 6-days post surgery) for each surgery occurring from patient entry into trial until 5 years post-dosing.

  8. Immune response to the hFIX transgene product (i.e., development of inhibitors) will be assessed by measurement of the level of inhibitors. [ Time Frame: From entry to 5 years post dosing ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who have previously received FLT180a within a clinical study.
  • Able to give full informed consent and able to comply with all requirements of the study including long-term follow-up for 14 years and 6 months.

Exclusion Criteria:


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03641703


Contacts
Layout table for location contacts
Contact: Clinical Operations +441438906870 contact@freeline.life

Locations
Layout table for location information
United Kingdom
Royal Free London NHS Foundation Tust Recruiting
London, United Kingdom
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom
Sponsors and Collaborators
Freeline Therapeutics

Layout table for additonal information
Responsible Party: Freeline Therapeutics
ClinicalTrials.gov Identifier: NCT03641703     History of Changes
Other Study ID Numbers: FLT180a-04
First Posted: August 22, 2018    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked