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Gene Therapy Trial Report

Summary

Gene Therapy for Haemophilia A.


NCTID NCT03001830 (View at clinicaltrials.gov)
Description
Development Status Active
Indication Hemophilia A
Disease Ontology Term DOID:12134
Compound Name AAV2/8-HLP-FVIII-V3
Sponsor University College, London
Funder Type Other
Recruitment Status
Active not recruiting
Enrollment Count 14 (ACTUAL)
Results Posted Not Available

Therapy Information


Target Gene/Variant F8
Therapy Type Gene transfer
Therapy Route In-vivo
Mechanism of Action Functional gene replacement
Route of Administration Intravenous
Drug Product Type Viral vector
Delivery System Viral transduction
Vector Type AAV2/8
Editor Type none
Dose 1 6E11 vg/kg (n=1)
Dose 2 2E12 vg/kg (n=2)
Dose 3 4E12 vg/kg
Dose 4 6E12 vg/kg

Study Record Dates


Current Stage Phase1, Phase2
Submit Date 2016-12-09
Completion Date 2029-12
Last Update 2025-03-05

Participation Criteria


Eligible Age >=18 Years
Standard Ages Adult, Older adult
Sexes Eligible for Study MALE
Eligibility Criteria
Inclusion criteria: 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. Exclusion criteria: 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
View Inclusion and Exclusion Criteria at ClinicalTrials.gov

Locations


No.of Trial Sites 4
Locations United States,United Kingdom

Regulatory Information


Has US IND True
FDA Designations
Recent Updates

Resources/Links