Hemophilia APhase 1NCT03818763

Gene Therapy Trial for Platelet Derived Factor VIII Production in Hemophilia A

A Phase 1 study testing Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII in people with Hemophilia A, run by Medical College of Wisconsin at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Hemophilia A
What is being tested?: Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 29 Apr 2020to 1 May 2033
Phase: Phase 1
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

Study population will include: adult males >18 years of age with a diagnosis of severe hemophilia A and currently active or a history of FVIII inhibitors (≥0.6 BU). Females will be excluded because hemophilia A is an X-linked disorder that is extremely rare in females.
Confirmed diagnosis of severe hemophilia A by undetectable plasma factor VIII:C by a one-stage PTT-based assay and coatest chromogenic factor VIII assay. Subjects with currently active or a history of positive FVIII inhibitor titers (≥0.6 BU) irrespective of their titer or current inhibitor status will be included for enrollment.
Subject may be prescribed prophylactic therapy with factor VIII bypassing agents or factor VIII mimetics prior to referral for inclusion in the study.
Subjects who are treated on demand using factor VIII bypassing agents must have a history of four or more bleeding episodes requiring treatment in the six-month period prior to referral for inclusion in the study.
Adequate bone marrow reserve as demonstrated by ANC >1.5/cu.mm; Hemoglobin >9g/dL; Platelets >100,000/microliter.
Adequate renal function, defined as creatinine clearance>60 ml/min (Cockroft-Gault formula)

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Adequate liver function, defined as defined as total bilirubin ≤1.5 times the upper limit of normal (ULN) (excluding Gilbert's syndrome), both AST and ALT ≤3 times ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis.
Subject must sign an informed consent after explanation of the study and having questions answered.
Subject must be willing and able to document type of bleeding episodes and treatment in a paper or electronic diary during the study.
Subject must be willing to return for regular follow-up visits during the 15-year study.

Who cannot join

A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.
Therapy with factor VIII with the intent of immune tolerance induction within 30 days prior to inclusion within the study.
Enrollment in another interventional clinical trial within 60 days prior to study inclusion.
Medical contraindication to PBSC cytokine mobilization, use of GCSF, PBSC apheresis procedure or conditioning regimen.
Medically significant organ dysfunction that would prevent compliance with conditioning or would severely limit the probability of survival based on clinical status.
Those with a known co-existing clinically significant thrombophilic disorder, or as determined by the presence of any of the below identified on screening laboratory assessments:

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FV Leiden
Protein S deficiency
Protein C deficiency
Prothrombin mutation (G20210A)
D-dimer >3 x the upper limit of normal (ULN) at Screening All known patients with the above and any patient with a personal or significant family history of thrombotic events (DVT, PE, arterial clots) as deemed by the principal investigator will be screened for the above disorders.
Active invasive malignancy (Non-melanoma skin cancers and carcinoma in situ are not excluded).
Known bone marrow disorders or abnormal bone marrow cytogenetics.
Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment.
Life expectancy severely limited by disease(s) other than hemophilia A.
Patients with HIV, hepatitis B, hepatitis C (with an AST/ALT > 3 times the upper limit of normal).
Other active infectious disease that is a contraindicat ion for immunosuppressive therapy.
Patients who have elective surgery scheduled during the study period.

Trial locations and contacts

1 site in 1 country.

United States1 site

Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: Phase I Study Evaluating Safety and Feasibility of Hematopoietic Stem Cell Gene Transfer That Targets Factor VIII Delivery From Platelets for Patients With Hemophilia A

This is a Phase I study. This research study is being conducted to find new ways to treat severe hemophilia A. This study is a gene therapy study. Gene therapy is an experimental way to introduce, into a person's cells, specific genetic material. A gene can be delivered/introduced into a cell using a carrier known as a "vector." In this study, a virus (lentivirus), the "vector", is used to introduce or deliver a gene that creates and stores a protein Factor VIII (FVIII) in your platelets. These platelets are made from stem cells (mother cells for your bone marrow) that are removed from your blood by a procedure called apheresis. This research study will take some of the patient's own stem cells, from the apheresis procedure, and genetically modify them using the vector in order to make them produce FVIII in platelets that arise from the stem cells. They will then give the genetically modified stem cells back to the patient so that they can possibly create platelets that produce and store Factor VIII on their own.

Read the detailed description

This is an open label, nonrandomized, single center, phase I cohort study, involving reduced intensity conditioning, followed by a single infusion of autologous CD34+PBSC, transduced with a lentiviral vector (-889ITGA2B-BDDFVIII-WPTS (MUT6)(VSVg)) also known as (Pleightlet(MUT6)) encoding the B domain deleted from of human coagulation factor VIII (BDDFVIII) in up to five hemophilia A patients with a history of FVIII inhibitors (≥0.6BU) .

Conditions: Hemophilia A
Being tested: Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII
Keywords: Gene Therapy
Medical subject headings: Hemophilia A

What participants receive

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

Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIIIBiological
Reduced intensity conditioning with melphalan and fludarabine, followed by a single infusion of autologous CD34+PBSC, transduced with a lentiviral vector (-889ITGA2B-BDDFVIII-WPTS(MUT6)(VSVg)) also known as (Pleightlet(MUT6)) encoding the B domain deleted from of human coagulation factor VIII (BDDFVIII) in up to five hemophilia A patients with a history of FVIII inhibitors (≥0.6BU).
The infusion volume of transduced cells will not exceed 20 ml/kg body weight.

Study groups in NCT03818763
Study group	Role	What they receive
Autologous CD34+PBSC transduced with a lentiviral vector	Experimental	Patients will receive a patient specific (autologous) cytokine mobilized CD34+Peripheral Blood Stem Cells (PBSC) transduced ex vivo with a lentiviral vector containing cDNA encoding the human B-domain deleted FVIII protein. Receives: Biological: Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII

What is being measured

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

Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion
Assessed by availability of ≥4x106 transduced clinical grade CD34+PBSC per kg meeting release criteria for infusion; undetectable microbiological contamination and cell viability ≥70%.
Measured: Through study completion, an average of 4 years

Secondary outcomes (1)

Incidence of toxicity from gene therapy
Number of events meeting CTCAE criteria grade 3 or 4 toxicity
Measured: Within 3 months of gene therapy infusion

Timeline

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

29 Apr 20201 May 2033

First posted28 Jan 2019
Study start29 Apr 2020
Primary completion31 Mar 2027 (estimated)
Study completion1 May 2033 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hemophilia AStudies of the same condition, open and under way.
More trials run by Medical College of WisconsinThe 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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Open-label, nonrandomized, single-center phase I cohort study
Masking: None (open label)
Enrolment: 5 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03818763
Sponsor's protocol ID: PRO00033763
Status last verified: Oct 2025
First submitted: 15 Jan 2019
Last updated: 13 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Eapen M, Malec LM, Armant MA, Johnson BD, Shi Q, Xu H, Du LM, Jerkins JH, Duffy LJ, Bushman FD, Lee C, Petrichenko A, Hematti P, Brazauskas R, Jobe SM, Hari PN, Wilcox DA. Platelet-Targeted Gene Therapy for Hemophilia A with Inhibitor History. N Engl J Med. 2025 Jan 23;392(4):412-414. doi: 10.1056/NEJMc2415164. No abstract available.
PubMed 39842018

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B

All Hemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study Evaluating Safety and Feasibility of Hematopoietic Stem Cell Gene Transfer That Targets Factor VIII Delivery From Platelets for Patients With Hemophilia A
ClinicalTrials.gov ID: NCT03818763
Acronym / sponsor ID: PRO00033763
Conditions: Hemophilia A
Keywords: Gene Therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 5 participants (estimated)
Lead sponsor: Medical College of WisconsinUniversity, hospital or other
Study start: 29 Apr 2020 (actual)
Primary completion: 31 Mar 2027 (estimated)
Study completion: 1 May 2033 (estimated)
First posted: 28 Jan 2019 (actual)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Open-label, nonrandomized, single-center phase I cohort study

Arm	Type	Receives
Autologous CD34+PBSC transduced with a lentiviral vector	Experimental	Biological: Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIIIPatients will receive a patient specific (autologous) cytokine mobilized CD34+Peripheral Blood Stem Cells (PBSC) transduced ex vivo with a lentiviral vector containing cDNA encoding the human B-domain deleted FVIII protein.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Study population will include: adult males >18 years of age with a diagnosis of severe hemophilia A and currently active or a history of FVIII inhibitors (≥0.6 BU). Females will be excluded because hemophilia A is an X-linked disorder that is extremely rare in females.
Confirmed diagnosis of severe hemophilia A by undetectable plasma factor VIII:C by a one-stage PTT-based assay and coatest chromogenic factor VIII assay. Subjects with currently active or a history of positive FVIII inhibitor titers (≥0.6 BU) irrespective of their titer or current inhibitor status will be included for enrollment.
Subject may be prescribed prophylactic therapy with factor VIII bypassing agents or factor VIII mimetics prior to referral for inclusion in the study.
Subjects who are treated on demand using factor VIII bypassing agents must have a history of four or more bleeding episodes requiring treatment in the six-month period prior to referral for inclusion in the study.
Adequate bone marrow reserve as demonstrated by ANC >1.5/cu.mm; Hemoglobin >9g/dL; Platelets >100,000/microliter.

Key exclusion criteria (18 listed)

A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.

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
Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIIIReduced intensity conditioning with melphalan and fludarabine, followed by a single infusion of autologous CD34+PBSC, transduced with a lentiviral vector (-889ITGA2B-BDDFVIII-WPTS(MUT6)(VSVg)) also known as (Pleightlet(MUT6)) encoding the B domain deleted from of human coagulation factor VIII (BDDFVIII) in up to five hemophilia A patients with a history of FVIII inhibitors (≥0.6BU). The infusion volume of transduced cells will not exceed 20 ml/kg body weight.	Biological	Autologous CD34+PBSC transduced with a lentiviral vector

Primary outcome

Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion
Time frame: Through study completion, an average of 4 years
Assessed by availability of ≥4x106 transduced clinical grade CD34+PBSC per kg meeting release criteria for infusion; undetectable microbiological contamination and cell viability ≥70%.

1 secondary outcome

Incidence of toxicity from gene therapy
Time frame: Within 3 months of gene therapy infusion

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 13 Jul 2026.
Background: PubMed 39842018Eapen M, Malec LM, Armant MA, Johnson BD, Shi Q, Xu H, Du LM, Jerkins JH, Duffy LJ, Bushman FD, Lee C, Petrichenko A, Hematti P, Brazauskas R, Jobe SM, Hari PN, Wilcox DA. Platelet-Targeted Gene Therapy for Hemophilia A with Inhibitor History. N Engl J Med. 2025 Jan 23;392(4):412-414. doi: 10.1056/NEJMc2415164. No abstract available.

Related trials for Hemophilia A

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B

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.

Mary Eapen, MD principal investigator

Froedtert Hosptial and Medical College of Wisconsin

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 10 inclusion and 18 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 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 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.

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?

Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion (time frame: Through study completion, an average of 4 years). 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 NCT03818763, 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 13 Jul 2026.