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

NCT03641703 | Terminated Phase 1

• 1 other identifier: FLT180a-04
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

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.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (2)

• 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).

  From entry to 5 years post dosing

• Durability of Response

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

  From entry to 5 years post dosing

Secondary Outcomes (12)

• Secondary Safety Measurement

  From entry to 5 years post dosing

• FIX Activity Levels at or below 150%

  From entry to 5 years post dosing

• FIX Activity Levels including 150% or above

  From entry to 5 years post dosing

• FIX Activity Levels - Change from baseline

  From entry to 5 years post dosing

• Haemostatic Effectiveness - Bleeding Rates

  From entry to 5 years post dosing

Study Arms (1)

FLT180a

EXPERIMENTAL

Participants who have received gene therapy vector (FLT180a)

Biological: FLT180a

Interventions

FLT180a BIOLOGICAL

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.

FLT180a

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• N/A

Sponsors & Collaborators

• Spur Therapeutics: lead

Study Sites (6)

The Haemophilia and Thrombosis Centre

Canterbury, Kent, CT13NG, United Kingdom

Location

Sheffield Teaching Hospital

Sheffield, South Yorkshire, S102JF, United Kingdom

Location

Royal Free London NHS Foundation Tust

London, United Kingdom

Location

Newcastle Hemophilia Comprehensive Care Centre

Newcastle, NE14LP, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

Southampton Haemophilia Comprehensive Care Centre

Southampton, SO166YD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35857660 DERIVED

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 22, 2018
• Study Start: July 10, 2018
• Primary Completion: May 24, 2023
• Study Completion: May 24, 2023
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)