Clinical trial NCT03641703: A Long-Term Follow-Up Study of Haemophilia B Patients Who Have Undergone Gene Therapy
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hemophilia B
Lead sponsor: Spur Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-08-22
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Primary Safety Measurement
timeFrame: From entry to 5 years post dosing
measure: Durability of Response
timeFrame: From entry to 5 years post dosing
Secondary outcomes:
measure: Secondary Safety Measurement
timeFrame: From entry to 5 years post dosing
measure: FIX Activity Levels at or below 150%
timeFrame: From entry to 5 years post dosing
measure: FIX Activity Levels including 150% or above
timeFrame: From entry to 5 years post dosing
measure: FIX Activity Levels - Change from baseline
timeFrame: From entry to 5 years post dosing
measure: Haemostatic Effectiveness - Bleeding Rates
timeFrame: From entry to 5 years post dosing
measure: Haemostatic Effectiveness - FIX Concentrate Consumption
timeFrame: From entry to 5 years post dosing
measure: 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)
timeFrame: From entry to 5 years post dosing
measure: 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)
timeFrame: From entry to 5 years post dosing
measure: 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)
timeFrame: From entry to 5 years post dosing
measure: 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)
timeFrame: From entry to 5 years post dosing
measure: Immune response to the hFIX transgene product (i.e., development of inhibitors) will be assessed by measurement of the level of inhibitors.
timeFrame: From entry to 5 years post dosing
measure: Clearance of vector genomes (vgs) in plasma, urine, saliva, stool and semen.
timeFrame: From entry to complete clearance of vgs in all sample pools.
Other outcomes:
Locations:
city: Canterbury
country: United Kingdom
facility: The Haemophilia and Thrombosis Centre
state: Kent
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital
state: South Yorkshire
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Tust
city: Newcastle
country: United Kingdom
facility: Newcastle Hemophilia Comprehensive Care Centre
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton Haemophilia Comprehensive Care Centre
Study officials:
References:
citation: Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K, Dolan G, Reiss U, Phillips M, Riddell A, Peralta MR, Quaye M, Patch DW, Tuddenham E, Dane A, Watissee M, Long A, Nathwani A. Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B. N Engl J Med. 2022 Jul 21;387(3):237-247. doi: 10.1056/NEJMoa2119913.