AzTrials
AzTrials

Hemophilia BPhase 1/2NCT03641703

A Long-Term Follow-Up Study of Haemophilia B Patients Who Have Undergone Gene Therapy

A Phase 1/2 study testing FLT180a in people with Hemophilia B, run by Spur Therapeutics at 6 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Hemophilia B
What is being tested?
FLT180a
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
6 sitesUnited Kingdom
Study dates
10 Jul 2018to 24 May 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • N/A

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United Kingdom6 sites

  • The Haemophilia and Thrombosis Centre

    Canterbury, Kent, CT13NG

  • Royal Free London NHS Foundation Tust

    London

  • Newcastle Hemophilia Comprehensive Care Centre

    Newcastle, NE14LP

  • Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Sheffield Teaching Hospital

    Sheffield, South Yorkshire, S102JF

  • Southampton Haemophilia Comprehensive Care Centre

    Southampton, SO166YD

Other trials in United Kingdom

About this study

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

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.

Conditions
Hemophilia B
Being tested
FLT180a
Medical subject headings
Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FLT180aBiological

    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 groups in NCT03641703
Study groupRoleWhat they receive
FLT180aExperimentalParticipants who have received gene therapy vector (FLT180a)
Receives: Biological: FLT180a

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary Safety Measurement

    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).

    Measured: From entry to 5 years post dosing

  2. Durability of Response

    Durability of response will be estimated by the rate of decline of the FIX activity observed from study entry (Primary Endpoint)

    Measured: From entry to 5 years post dosing

Secondary outcomes (12)

  1. Secondary Safety Measurement

    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.

    Measured: From entry to 5 years post dosing

  2. FIX Activity Levels at or below 150%

    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.

    Measured: From entry to 5 years post dosing

  3. FIX Activity Levels including 150% or above

    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.

    Measured: From entry to 5 years post dosing

  4. FIX Activity Levels - Change from baseline

    Change from baseline (prior to FLT180a dosing) in FIX activity at each scheduled visit.

    Measured: From entry to 5 years post dosing

  5. Haemostatic Effectiveness - Bleeding Rates

    Change from baseline (prior to FLT180a dosing) in annualised bleeding rate by measurement of number of breakthrough bleeding episodes.

    Measured: From entry to 5 years post dosing

  6. Haemostatic Effectiveness - FIX Concentrate Consumption

    Change from baseline (prior to FLT180a dosing) in FIX concentrate consumption by measurement of factor concentrate consumed by the patient.

    Measured: From entry to 5 years post dosing

  7. 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)

    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.

    Measured: From entry to 5 years post dosing

  8. 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)

    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.

    Measured: From entry to 5 years post dosing

  9. 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)

    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.

    Measured: From entry to 5 years post dosing

  10. 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)

    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.

    Measured: From entry to 5 years post dosing

  11. Immune response to the hFIX transgene product (i.e., development of inhibitors) will be assessed by measurement of the level of inhibitors.

    Samples will be taken to capture development of inhibitors overtime.

    Measured: From entry to 5 years post dosing

  12. Clearance of vector genomes (vgs) in plasma, urine, saliva, stool and semen.

    Samples from each pool will be taken at each visit until there have been 3 consecutive samples that are negative for vgs.

    Measured: From entry to complete clearance of vgs in all sample pools.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Aug 2018
  2. Study start10 Jul 2018
  3. Primary completion24 May 2023
  4. Study completion24 May 2023

Why it stopped: Freeline has decided to pause development of FLT180a for business priorities

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03641703
Sponsor's protocol ID
FLT180a-04
Status last verified
Jul 2023
First submitted
27 Jul 2018
Last updated
20 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35857660

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing FLT180a in people with Hemophilia B, run by Spur Therapeutics at 6 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Freeline has decided to pause development of FLT180a for business priorities). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Safety Measurement (time frame: From entry to 5 years post dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03641703, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in