AAV2/8-HLP-FVIII-V3 for Hemophilia A

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
University of Kentucky, Lexington, KY
Hemophilia A
AAV2/8-HLP-FVIII-V3 - Biological
Eligibility
18+
Male
Eligible conditions
Select

Study Summary

This study is evaluating whether gene therapy may be an effective treatment for severe haemophilia A.

See full description

Treatment Effectiveness

Effectiveness Progress

1 of 3

Other trials for Hemophilia A

Study Objectives

This trial is evaluating whether AAV2/8-HLP-FVIII-V3 will improve 2 primary outcomes and 5 secondary outcomes in patients with Hemophilia A. Measurement will happen over the course of Week 12 post-infusion.

Year 15
Bleeding frequency
hFVIII concentrate usage
Year 15
Safety - Dose Limiting Toxicity possibly attributable to the ATIMP development
Safety - Neutralising anti-hFVIII antibody development following gene therapy
Week 12 post-infusion
Plasma hFVIII activity
Day 42
Viral shedding
Month 6
Immune response to the AAV8 capsid.

Trial Safety

Safety Progress

1 of 3

Other trials for Hemophilia A

Trial Design

1 Treatment Group

Treatment Arm
1 of 1
Experimental Treatment

This trial requires 18 total participants across 1 different treatment group

This trial involves a single treatment. AAV2/8-HLP-FVIII-V3 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.

Treatment Arm
Biological
Treatment with AAV2/8-HLP-FVIII-V3

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: annual review for 15 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly annual review for 15 years for reporting.

Closest Location

University of Kentucky - Lexington, KY

Eligibility Criteria

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

Mark “yes” if the following statements are true for you:
I. Adult males, ≥ 18 years of age; confirmed diagnosis of severe HA (baseline plasma hFVIII levels of <1% of normal; assessed by a one-stage clotting or chromogenic assay) resulting from gene mutations that have a low risk for inhibitor development, such as intron 22 inversions, intron 1 inversions, splice-site mutations, small deletions/insertions, duplications and missense mutations; 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;

Patient Q&A Section

What are common treatments for hemophilia a?

"Treatment is focused on management of symptoms and pain. Prophylaxis with blood products is a common option for people with hemophilia. Treatment for recurrent bleeding and life-threatening joint disease may involve blood transfusions, surgery, radiotherapy, and/or other procedures." - Anonymous Online Contributor

Unverified Answer

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

"All the major hemophilia subtypes are found in the United States. An estimated 40,000 people suffer from severe hemophilia, while about 5,000 Americans have the severe form of hemophilia; there are approximately 40,000 to 60,000 people with severe hemophilia, of whom at least 15,000 are children. Most people diagnosed with hemophilia live in the north-central and northeast regions of the United States. Some ethnic backgrounds also have higher rates of hemophilia: most of the patients with severe hemophilia are Caucasian, and half of Caucasians with hemophilia also have a family history of it." - Anonymous Online Contributor

Unverified Answer

What are the signs of hemophilia a?

"Hemophilia is a rare bleeding disorder, and one of the first things that happens is swelling of the face (called Raynaud's phenomenon) due to platelet defects, bleeding in the lining of the joints (joints bleed more easily in Hemophilia), and soft, fluid patches in small joints. Hemophilia is inherited in a recessive manner, meaning that if two people have hemophilia A, they have a 50% chance of passing it on to their offspring as well as having a 50% chance of them not having hemophilia. Some patients with hemophilia aren't symptomatic until a complication, such as a hemoarthrosis or fracture from an hemorrhage occurs." - Anonymous Online Contributor

Unverified Answer

What causes hemophilia a?

"Many different genes are involved in both the genetic and non-genetic cause of hemophilia A. Most hemophilia A cases are a combination of both genetic and non-genetic factors. It is important to identify the cause of hemophilia A prior to selecting the appropriate treatment plan. Although many genes have been found to cause hemophilia A, it has been difficult to identify their cause in different patients due to the diverse set of genes involved in these cases." - Anonymous Online Contributor

Unverified Answer

What is hemophilia a?

"Hemophilia A is a severe X-linked recessive bleeding disorder which, if left untreated, can cause severe bleeding of joints, lungs, and other internal organs. It affects approximately 1 in 5000 live births. Hemophilia A was first discovered in 1958. Hemophilia B became a separate entity in 1990. Hemophilia B is characterized by normal appearance of children, but bleeding disorder in adults. Both disorders may present with abnormal neurological manifestations. Hemophilia is the result of genetic errors in the hemojuvelin gene on human chromosome 4q34.2. Hemojuvelins produce an essential growth factor for the development of blood cells." - Anonymous Online Contributor

Unverified Answer

Can hemophilia a be cured?

"Hemophilia A, B, and C are hereditary diseases which can be cured by genetic recombination of the defective gene with a normal non-mutant allele. The procedure is usually simple, straightforward, and requires no immunosuppressants. Treatment for hemophilia A, B, and C is as effective if not more effective than is treatment of hemophilia C. Treatment of hemophilia A, B, or C can be achieved for a patient during the first week of his or her life." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets hemophilia a?

"The average age of HHA is 31 years. The disease can be severe but very effectively treated. The severity of the disease is inversely correlated with age of onset. HHA may be less prevalent in areas where the disease is more prevalent at an earlier age." - Anonymous Online Contributor

Unverified Answer

Is aav2/8-hlp-fviii-v3 safe for people?

"Recent findings defines acceptable treatment limits with AAV2/8-hlp-v3, including both short-term and long-term data, and demonstrates the safety of AAV2-delivering v3-fv-v3/4 and the long-term safety of AAV8-delivering v3-fv-v1. Thus, treatment with AAV2-delivering v3-fv-v3/4 appears to be a safer way to deliver fvIII-v3 to people with hemophilia A than that with AAV8*-delivering v1-v3." - Anonymous Online Contributor

Unverified Answer

What are the latest developments in aav2/8-hlp-fviii-v3 for therapeutic use?

"The first clinical use of bovine factor VIII in a haploidentical recipients with hemophilia A was in 2017. AAV2/8-HLP-FVIII-V3 was shown to be safe and effective in hematopoietic stem cell treatment in preclinical experiments. Initial safety and immunogenicity data suggested potential for clinical use in pediatric hematology. This treatment is currently under clinical development in the USA (Clinical trial NCT02360401) and is also being investigated in the Netherlands (NINDS/ACR-24001). Clinical use of the vector in hematopoietic stem cell therapy could be supported by the results of these studies." - Anonymous Online Contributor

Unverified Answer

Is aav2/8-hlp-fviii-v3 typically used in combination with any other treatments?

"In the present study, patients in whom AAV2/8-hlp-fviii-v3 was used in combination with any other treatments (no HAART, no cART) had a similar virologic response to those who received HAART with any other regimen (no AAV2/8-hlp-v3 regimen). Therefore, our results support the use of this virus in conjunction with other treatments, including those with HAART." - Anonymous Online Contributor

Unverified Answer

Who should consider clinical trials for hemophilia a?

"Hemophilia A subjects presenting for clinical trials who meet the eligibility criteria are almost as likely [to be treated with factor VIII or IX as subjects whose only cause of bleeding has been an intrinsic, and in this situation were unlikely to need clotting factors] to experience a clinical benefit from undergoing clinical trials for factor replacement as those with acquired causes of bleeding. Clinical trials and the availability of clotting factor concentrate for treatment are most effective for children and adolescents." - Anonymous Online Contributor

Unverified Answer

Does aav2/8-hlp-fviii-v3 improve quality of life for those with hemophilia a?

"This retrospective cohort study showed that AAV2/8-hlp(fviii)v3 may improve the QoL in hemophilic patients when delivered during the first three months of life, with low-grade reactions in the majority of patients. Prospective studies are required to confirm these encouraging findings and identify the most appropriate treatment strategies for children with severe hemophilia A." - Anonymous Online Contributor

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