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A Long-Term Follow-Up 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03641703
Recruitment Status : Active, not recruiting
First Posted : August 22, 2018
Last Update Posted : December 1, 2020
Sponsor:
Information provided by (Responsible Party):
Freeline Therapeutics

Tracking Information
First Submitted Date  ICMJE July 27, 2018
First Posted Date  ICMJE August 22, 2018
Last Update Posted Date December 1, 2020
Actual Study Start Date  ICMJE July 10, 2018
Estimated Primary Completion Date December 31, 2035   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
  • Primary Safety Measurement [ Time Frame: From entry to 5 years post dosing ]
    Frequency of treatment-emergent adverse events/reactions (AE/ARs) reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or later (Primary Safety).
  • Durability of Response [ Time Frame: From entry to 5 years post dosing ]
    Durability of response will be estimated by the rate of decline of the FIX activity observed from study entry (Primary Endpoint)
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • 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 ]
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
  • Secondary Safety Measurement [ Time Frame: From entry to 5 years post dosing ]
    Frequency of reporting of abnormal or change from baseline findings from safety assessments including laboratory assessments, vital signs, physical exam and liver ultrasound according to common terminology criteria for Adverse Events (CTCAE) version 5.0 or later.
  • FIX Activity Levels at or below 150% [ Time Frame: From entry to 5 years post dosing ]
    Samples will be taken at each visit to measure FIX activity levels and the proportion of patients achieving FIX activity at or above 5%, 15%, 30%, 40%, 50%, 70% but no more than 150% of normal at each scheduled visit.
  • FIX Activity Levels including 150% or above [ Time Frame: From entry to 5 years post dosing ]
    Samples will be taken at each visit to measure FIX activity levels and the proportion of patients achieving FIX activity at or above 5%, 15%, 30%, 40%, 50%, 70% and 150% of normal at each required visit.
  • FIX Activity Levels - Change from baseline [ Time Frame: From entry to 5 years post dosing ]
    Change from baseline (prior to FLT180a dosing) in FIX activity at each scheduled visit.
  • Haemostatic Effectiveness - Bleeding Rates [ Time Frame: From entry to 5 years post dosing ]
    Change from baseline (prior to FLT180a dosing) in annualised bleeding rate by measurement of number of breakthrough bleeding episodes.
  • Haemostatic Effectiveness - FIX Concentrate Consumption [ Time Frame: From entry to 5 years post dosing ]
    Change from baseline (prior to FLT180a dosing) in FIX concentrate consumption by measurement of factor concentrate consumed by the patient.
  • 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) [ 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 time of discharge or 6-days post surgery) for each surgery occurring from patient entry into trial until 5 years post-dosing.
  • 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) [ 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.
  • 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) [ 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.
  • 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) [ 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.
  • 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 ]
    Samples will be taken to capture development of inhibitors overtime.
  • Clearance of vector genomes (vgs) in plasma, urine, saliva, stool and semen. [ Time Frame: From entry to complete clearance of vgs in all sample pools. ]
    Samples from each pool will be taken at each visit until there have been 3 consecutive samples that are negative for vgs.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Long-Term Follow-Up Study of Haemophilia B Patients Who Have Undergone Gene Therapy
Official Title  ICMJE 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
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 after being dosed. Participants will undergo procedures including physical examinations, join assessments, 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia B
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: FLT180a
Participants who have received gene therapy vector (FLT180a)
Intervention: Biological: FLT180a
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 30, 2020)
10
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2018)
50
Estimated Study Completion Date  ICMJE December 31, 2035
Estimated Primary Completion Date December 31, 2035   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 the time frame the study requires.
  • Willing to practice barrier contraception until at least three consecutive semen samples after vector administration are negative for vector sequences.

Exclusion Criteria:

N/A

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03641703
Other Study ID Numbers  ICMJE FLT180a-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Freeline Therapeutics
Study Sponsor  ICMJE Freeline Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Freeline Therapeutics
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP