Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII for Hemophilia A

Phase-Based Estimates
1
Effectiveness
1
Safety
Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, WI
Hemophilia A
Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII - Biological
Eligibility
18+
Male
Eligible conditions
Hemophilia A

Study Summary

This study is evaluating whether a new type of gene therapy may help individuals with severe hemophilia A.

See full description

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII will improve 1 primary outcome and 1 secondary outcome in patients with Hemophilia A. Measurement will happen over the course of Within 3 months of gene therapy infusion.

Year 4
Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion
Month 3
Incidence of toxicity from gene therapy

Trial Safety

Safety Estimate

1 of 3

Trial Design

2 Treatment Groups

Control
Autologous CD34+PBSC transduced with a lentiviral vector

This trial requires 5 total participants across 2 different treatment groups

This trial involves 2 different treatments. Auto CD34+PBSC, Transduced With A Lentiviral Vector Encoding The B Domain Deleted From Of Human Coagulation Factor VIII is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

Autologous CD34+PBSC transduced with a lentiviral vector
Biological
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.
ControlNo treatment in the control group

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: through study completion, an average of 4 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly through study completion, an average of 4 years for reporting.

Who is running the study

Principal Investigator
M. E. M.
Prof. Mary Eapen MBBS, Professor
Medical College of Wisconsin

Closest Location

Froedtert Hospital and the Medical College of Wisconsin - Milwaukee, WI

Eligibility Criteria

This trial is for male patients aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Study population will include: adult males > 18 years old who have a diagnosis of severe hemophilia A and are currently active or have a history of FVIII inhibitors (≥ 0.6 BU) show original
We confirmed the diagnosis of severe hemophilia A by undetectable levels of factor VIII:C as measured by a one-stage PTT-based assay and a coatest chromogenic factor VIII assay show original
The patient has an adequate bone marrow reserve, as evidenced by an ANC of more than 1.5/cu.mm, a hemoglobin level of more than 9g/dL, and a platelet count of more than 100,000/microliter. show original
and/or proteinuria <3.5g/24 hrs (urine dipstick) are required for initiation of therapy People with adequate renal function (creatinine clearance>60 ml/min or proteinuria <3.5g/24 hrs) are able to start taking the medication. show original
The subject must sign an informed consent form after being informed of the study and answering any questions. show original
Participants in the study must be willing and able to document their type of bleeding episodes and treatment in a paper or electronic diary during the study. show original
We need someone who is willing to come back for regular follow-up visits over the next 15 years. show original
People who need treatment for factor VIII deficiency must have had four or more episodes of bleeding that required treatment in the six months prior to being referred to the study. show original
The patient has adequate liver function if their total bilirubin is ≤1.5 times the upper limit of normal, their AST and ALT are both ≤3 times the upper limit of normal, and they have no clinical signs or laboratory/radiographic evidence of cirrhosis. show original
The subject may be prescribed prophylactic therapy with a factor VIII bypassing agent or factor VIII mimetic prior to referral for inclusion in the study. show original

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are common treatments for hemophilia a?

Add answer

Hemophilia is typically treated within the first few years after birth by replacement of missing factors by transfusion and when needed, splenic or bone marrow transplantation. Immunomodulators such as interferon alpha may also be used. The long term prognosis is determined by the degree of bleeding tendency in the affected person and is inversely related to the level of activity of factor VIII in the body.

Unverified Answer

How many people get hemophilia a a year in the United States?

Add answer

There are about one million cases of hemophilia in the United States, about 3.5 million hemophilia A and one million hemophilia B cases, making it the second most common genetic blood disease in the United States.

Unverified Answer

What is hemophilia a?

Add answer

Hemophilia B is the most common hemophilia and an X-linked recessive disease that is characterized by an absence of blood clotting. Treatment for hemophilia A is limited in scope to correction of bleeding events in children and adults. Older patients, especially those over 50 years of age, are susceptible to bleeding into joints, muscles, and the skin. Older patients also develop hemodilution, which may make them more susceptible to bruising and excessive bleeding. Hemophilia B occurs about as often in males as females.\n

Unverified Answer

Can hemophilia a be cured?

Add answer

Hemophilia can be prevented by gene and FVIII transfusion. Hemophilia may be effectively treated by FVIII replacement therapy. Heparin can be used to prevent thrombosis, especially for infants without anticoagulation therapy.

Unverified Answer

What causes hemophilia a?

Add answer

There are various types of hemophilia which lead to different symptoms and signs. Genetic traits and environmental factors (exposure to trauma and trauma-related exposures) are thought to contribute to the expression of these traits. Exposure to blood products in utero may play a role. Hemophiliac babies are screened for hemophilia a, in the form of an immunological technique to detect antibodies found in babies of homozygous carriers of the factor VIII gene. These antibodies would persist postnatally, as the child would be exposed to blood products later in life through prophylaxis. If the child has the gene, he or she will be affected by the disease.

Unverified Answer

What are the signs of hemophilia a?

Add answer

Signs of hemophilia a include bleeding tendencies and clotting factors. They may include prolonged bleeding time, bleeding time after surgery, petechiae from trauma, or bruising from surgery. An infant with a history of bleeding problems or bruising from trauma should be assessed by hematologist, which may be necessary for hemostatic factors. There are no standard bleeding time tests for hemophilia a; however, the following tests should be done to help determine the severity of the clotting deficiencies:\n1. Coagulation factor tests\n2. Immunoassay for von Willebrand factor (vWF)\n3.

Unverified Answer

What does auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii usually treat?

Add answer

Autologous CD34(+) pbsc(+) PBMC transduced by a lentiviral vector encoding the b domain deleted from of human coagulation factor viii resulted in durable, safe and efficient hematopoietic recovery from an immunodeficient patient with hemophilia a.

Unverified Answer

Is auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii typically used in combination with any other treatments?

Add answer

The data suggest that hbF-viii vector/CD34 can be used alone or with other drug treatments; however, it cannot be recommended as a stand-alone treatment for treatment of thrombocytopaenia\n.

Unverified Answer

How does auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii work?

Add answer

A gene therapy approach in which CD34+ PBPCs are genetically engineered with the b domain deleted from Factor VIII has been successfully developed. As shown in several animal models, gene transfer into these cells resulted in functional recovery after a transfusion by the treated CD34+ cells in hemophilic mice. Moreover, in vitro, transduced CD34+ PBPCs have been found to proliferate in the presence of hemophilus factor. In addition, gene therapy with CD34+ PBPCs could be safely administered without undue toxicity. Results from a recent clinical trial constitute further proof of concept to develop a feasible and safe gene therapy protocol for the treatment of hemophilic patients.

Unverified Answer

Does auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii improve quality of life for those with hemophilia a?

Add answer

The present data suggest that the CD34(+):p(bpdc) vector containing the B domain from FVIII improves HXQOL compared to FVIII as evidenced by the effect on the K-6 score. Further investigations of this strategy to address these deficits may therefore have great therapeutic promise.

Unverified Answer

What are the latest developments in auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii for therapeutic use?

Add answer

This approach may provide an efficient and highly effective treatment of hematologic malignancies with low risk of toxic side effects. Recent findings suggest that the use of an RNAi-mediated strategy to selectively silence the gene encoding Pbsc on the gene-transduced CD34+ cells might allow the elimination of leukemic CD34+ cells without interference with normal hematopoiesis.

Unverified Answer

Is auto cd34+pbsc, transduced with a lentiviral vector encoding the b domain deleted from of human coagulation factor viii safe for people?

Add answer

Autologous gene therapy using gene-engineered autologous coagulation factor replacement vectors is well tolerated and effective for alleviating the hemophobia symptoms in people with hemophilia A. A lentiviral vector encoding a cDNA encoding a b domain deficient form of human coagulation factor VIII (vIII bdomain-deleted) is effective for gene insertions into autologous CD34+ cells without significant toxicity or genotoxicity.

Unverified Answer
See if you qualify for this trial
Get access to this novel treatment for Hemophilia A by sharing your contact details with the study coordinator.