Hemophilia APhase 1/2GO-8NCT03001830
Gene Therapy for Haemophilia A.
A Phase 1/2 study testing AAV2/8-HLP-FVIII-V3 in people with Hemophilia A, run by University College, London at 4 sites in 2 countries.
Trial summary
The GO-8 study focuses on assessing safety and efficacy of gene therapy for patients with severe haemophilia A Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- AAV2/8-HLP-FVIII-V3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 14 Jun 2017to Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- 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.
Who cannot join
- 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).
- 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).
- Patients with a CHA2DS2-VASc score of 2 and above
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
St. Luke'S Regional Medical Center, Ltd
Boise, Idaho, 83712
University of Kentucky
Lexington, Kentucky, 40506
St Jude's Children's Research Hospital
Memphis, Tennessee, 38105-3678
About this study
Official title: GO-8: Gene Therapy for Haemophilia A Using a Novel Serotype 8 Capsid Pseudotyped Adeno-associated Viral Vector Encoding Factor VIII-V3
The GO-8 study focuses on assessing safety and efficacy of gene therapy for patients with severe haemophilia A
Read the detailed description
Haemophilia A is an x-linked, life threatening bleeding disorder arising from defects in the coagulation factor VIII (FVIII) gene. Current treatment for haemophilia A, the commonest inherited bleeding disorder (prevalence of 1 in 5000 individuals) consists of life-long, 2-3 times/week, intravenous injection of clotting factor concentrates, which is demanding and expensive. In contrast, gene therapy offers the potential of a cure for haemophilia A. In a previous gene therapy study in haemophilia B the investigators showed that a single intravenous administration of a serotype 8 based adeno-associated virus, (AAV8) vector encoding the factor IX (FIX) gene resulted in stable (>6 years) therapeutic expression of FIX without long-lasting toxicity. The investigators plan to use the same AAV8 platform to evaluate a novel FVIII expression cassette, AAV2/8-HLP-FVIII-V3, in patient with haemophilia A. Extensive preclinical studies demonstrate that AAV2/8-HLP-FVIII-V3 leads to long-term, endogenous expression of FVIII in mouse and non-human primate models without toxicity even when twenty-fold higher doses than the proposed starting clinical trial dose were used. Therefore, an open label, Phase I/II dose escalation study entailing a single systemic administration of AAV2/8-HLP-FVIII-V3 in adults (>18 years of age) with severe haemophilia A who have baseline factor FVIII levels of <1% of normal has been designed to establish safety and efficacy of our approach. Dosing will begin at 6x10^11 vector genome (vg)/kg progressing sequentially to 2x10^12vg/kg and ultimately 6x10^12vg/kg in the absence of toxicity. A minimum of 2 patients will be recruited at each dose with a possibility of expanding the dose cohort to a maximum of 6 patients based on safety and efficacy. The study duration for each patient will be 5 years after vector infusion.
- Conditions
- Hemophilia A
- Being tested
- AAV2/8-HLP-FVIII-V3
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV2/8-HLP-FVIII-V3Biological
Infusion of AAV2/8-HLP-FVIII-V3
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Treatment with AAV2/8-HLP-FVIII-V3 Receives: Biological: AAV2/8-HLP-FVIII-V3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Up to 5 years post-infusion
Secondary outcomes (5)
Plasma hFVIII activity
Assessments of plasma hFVIII activity
Measured: Regularly up to 5 years post-infusion
Bleeding frequency
Assessment of bleeding frequency using participant diaries before and after gene transfer
Measured: Annual review for 5 years
hFVIII concentrate usage
Assessment of hFVIII concentrate usage as per participant treatment records before and after gene transfer
Measured: Annual review for 5 years
Immune response to the AAV8 capsid.
Immune response to the AAV8 capsid will be assessed by measurement of the AAV8 antibody titre (humoral response) in plasma samples collected at various time points after gene transfer. Cellular immune response to AAV capsid will be determined using gamma interferon (IFNγ) ELIspot assay to AAV8 capsid
Measured: Weeks 3, 6, 9 & 12, month 6 and annually post-infusion to Year 5
Viral shedding
Serum and bodily secretions will be collected to assess clearance of vector genomes
Measured: Weekly from 7 days post infusion until sample clearance.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2016 (estimated)
- Study start14 Jun 2017
- Primary completionJan 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Pratima Chowdary, MD, Principal investigator, Royal Free London NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03001830
- Sponsor's protocol ID
- UCL 13/0076
- Other IDs
- 2016-000925-38, MR/L013185/1, 2016
- Acronym
- GO-8
- Status last verified
- Feb 2025
- First submitted
- 9 Dec 2016
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GO-8: Gene Therapy for Haemophilia A Using a Novel Serotype 8 Capsid Pseudotyped Adeno-associated Viral Vector Encoding Factor VIII-V3
- ClinicalTrials.gov ID
- NCT03001830
- Acronym / sponsor ID
- GO-8 / UCL 13/0076
- Conditions
- Hemophilia A
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 23 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The GO-8 study focuses on assessing safety and efficacy of gene therapy for patients with severe haemophilia A
Detailed description
Haemophilia A is an x-linked, life threatening bleeding disorder arising from defects in the coagulation factor VIII (FVIII) gene. Current treatment for haemophilia A, the commonest inherited bleeding disorder (prevalence of 1 in 5000 individuals) consists of life-long, 2-3 times/week, intravenous injection of clotting factor concentrates, which is demanding and expensive. In contrast, gene therapy offers the potential of a cure for haemophilia A. In a previous gene therapy study in haemophilia B the investigators showed that a single intravenous administration of a serotype 8 based adeno-associated virus, (AAV8) vector encoding the factor IX (FIX) gene resulted in stable (>6 years) therapeutic expression of FIX without long-lasting toxicity. The investigators plan to use the same AAV8 platform to evaluate a novel FVIII expression cassette, AAV2/8-HLP-FVIII-V3, in patient with haemophilia A. Extensive preclinical studies demonstrate that AAV2/8-HLP-FVIII-V3 leads to long-term, endogenous expression of FVIII in mouse and non-human primate models without toxicity even when twenty-fold higher doses than the proposed starting clinical trial dose were used. Therefore, an open label, Phase I/II dose escalation study entailing a single systemic administration of AAV2/8-HLP-FVIII-V3 in adults (>18 years of age) with severe haemophilia A who have baseline factor FVIII levels of <1% of normal has been designed to establish safety and efficacy of our approach. Dosing will begin at 6x10^11 vector genome (vg)/kg progressing sequentially to 2x10^12vg/kg and ultimately 6x10^12vg/kg in the absence of toxicity. A minimum of 2 patients will be recruited at each dose with a possibility of expanding the dose cohort to a maximum of 6 patients based on safety and efficacy. The study duration for each patient will be 5 years after vector infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Biological: AAV2/8-HLP-FVIII-V3Treatment with AAV2/8-HLP-FVIII-V3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (3 listed)
- 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).
- 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).
- Patients with a CHA2DS2-VASc score of 2 and above
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV2/8-HLP-FVIII-V3Infusion of AAV2/8-HLP-FVIII-V3 | Biological | Treatment Arm |
Primary outcome
Safety - Dose Limiting Toxicity possibly attributable to the gene therapy
Time frame: Up to 5 years post-infusion
Toxicity will be assessed according to CTCAE, version 4.03 based on the monitoring schedule which comprises a number of clinical and laboratory evaluations
Safety - Neutralising anti-hFVIII antibody development following gene therapy
Time frame: Up to 5 years post-infusion
The presence of neutralising hFVIII antibodies will be assessed by regular laboratory tests during patient follow up post infusion
5 secondary outcomes
Plasma hFVIII activity
Time frame: Regularly up to 5 years post-infusion
Bleeding frequency
Time frame: Annual review for 5 years
hFVIII concentrate usage
Time frame: Annual review for 5 years
Immune response to the AAV8 capsid.
Time frame: Weeks 3, 6, 9 & 12, month 6 and annually post-infusion to Year 5
Viral shedding
Time frame: Weekly from 7 days post infusion until sample clearance.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pratima Chowdary, MD principal investigator
Royal Free London NHS Foundation Trust
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AAV2/8-HLP-FVIII-V3 in people with Hemophilia A, run by University College, London at 4 sites in 2 countries.
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 1 inclusion and 3 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: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, 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?
This study is still under way. Results are not available in the source record yet.
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?
Safety - Dose Limiting Toxicity possibly attributable to the gene therapy (time frame: Up to 5 years post-infusion). 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?
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 5 Mar 2025.