Gene Therapy for Haemophilia A.

NCT03001830 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCL 13/00762016-000925-38MR/L013185/1
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 4

Brief Summary

The GO-8 study focuses on assessing safety and efficacy of gene therapy for patients with severe haemophilia A

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Safety - Dose Limiting Toxicity possibly attributable to the gene therapy

  Toxicity will be assessed according to CTCAE, version 4.03 based on the monitoring schedule which comprises a number of clinical and laboratory evaluations

  Up to 5 years post-infusion

• Safety - Neutralising anti-hFVIII antibody development following gene therapy

  The presence of neutralising hFVIII antibodies will be assessed by regular laboratory tests during patient follow up post infusion

  Up to 5 years post-infusion

Secondary Outcomes (5)

• Plasma hFVIII activity

  Regularly up to 5 years post-infusion

• Bleeding frequency

  Annual review for 5 years

• hFVIII concentrate usage

  Annual review for 5 years

• Immune response to the AAV8 capsid.

  Weeks 3, 6, 9 & 12, month 6 and annually post-infusion to Year 5

• Viral shedding

  Weekly from 7 days post infusion until sample clearance.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Treatment with AAV2/8-HLP-FVIII-V3

Biological: AAV2/8-HLP-FVIII-V3

Interventions

AAV2/8-HLP-FVIII-V3 BIOLOGICAL

Infusion of AAV2/8-HLP-FVIII-V3

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• I. Adult males, ≥ 18 years of age; confirmed diagnosis of severe haemophilia A (baseline plasma hFVIII levels of \<1% of normal; assessed by a one-stage clotting or chromogenic assay) II. A severe bleeding phenotype as defined by at least one of the following: (a) On prophylaxis for a history of bleeding or (b) On demand therapy with a current or past history of 4 or more bleeding episodes/year or (c) evidence of chronic haemophilic arthropathy (pain, joint damage, and loss of range of motion) III. Received treatment with hFVIII concentrates with at least \>50 exposure days; IV. Able to give full informed consent and able to comply with all requirements of the trial including 5-year long-term follow-up; V. Willing to practice barrier contraception until at least three consecutive semen samples after vector administration are below the sensitivity of the assay for vector sequences.

You may not qualify if:

• VI. Presence of neutralising anti-hFVIII antibodies (inhibitor, determined by the Bethesda inhibitor assay) at the time of enrolment or a previous history of hFVIII inhibitor on at least two occasions that required clinical management ; VII. Use of investigational therapy for haemophilia within 30 days before enrolment; VIII. Subjects with active hepatitis B or C, and HBsAg or hepatitis C RNA viral load positivity, respectively or currently on antiviral therapy for hepatitis B or C. (Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearers and those who have cleared hepatitis C on antiviral therapy are eligible).
• IX. Serological evidence of HIV; X. Evidence of liver dysfunction (persistently elevated alanine transaminase \>1.5 times upper limit of normal); XI. Uncontrolled glaucoma, diabetes mellitus, or hypertension (systolic BP consistently ≥140 mmHg or diastolic BP consistently ≥90 mmHg); XII. Any disease or condition (including cancer) at the physician's discretion that would prevent the patient from fully complying with the requirements of the study.; XIII. Suspicious lung lesions on CT scan that raise the possibility of cancer or premalignant pathology (based on chest CT scan done at screening or within 6 months prior to the screening visit) XIV. Presence of liver abnormality that is suspicious of malignancy on screening liver ultrasound XV. Patients with uncontrolled cardiac failure or unstable angina; XVI. Detectable neutralising anti-AAV8 antibodies XVII. Received an AAV vector, or any other gene transfer agent in the previous 6 months except for vaccines XVIII. History of active tuberculosis, fungal disease or other chronic infection XIX. Subjects who are unwilling to provide the required semen samples XX. Poor performance status (WHO score \>1) XXI. Patients at high risk of thromboembolic events (high risk patients would include those with a history of arterial or venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism, non-haemorrhagic stroke, arterial embolus) and those with acquired thrombophilia including conditions such as atrial fibrillation).
• XXII. Patients with a CHA2DS2-VASc score of 2 and above

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator

Study Sites (4)

St. Luke'S Regional Medical Center, Ltd

Boise, Idaho, 83712, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

St Jude's Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

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

Study Officials

• Pratima Chowdary, MD

  Royal Free London NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 9, 2016
• First Posted: December 23, 2016
• Study Start: June 14, 2017
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (1)