Gene Therapy for Hemophilia B

No longer recruiting at 45 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: UniQure Biopharma B.V.

Must be taking: Factor IX prophylaxis

Must not be taking: Experimental agents

Disqualifiers: HIV, Hepatitis B/C, Gene therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Single dose

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called AMT-061 (also known as AAV5-hFIXco-Padua) for individuals with hemophilia B, a condition where blood doesn't clot properly. The goal is to determine if a single dose can reduce bleeding episodes and improve safety. Participants will either receive the gene therapy or continue their usual treatment during a lead-in period. Men with severe or moderately severe hemophilia B who are already using regular factor IX treatments might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for hemophilia B.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, since participants must be on factor IX prophylaxis, you will likely need to continue that treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that AMT-061, the gene therapy being tested for hemophilia B, is generally safe and well-tolerated. In earlier studies, patients did not require medication to lower their immune response after receiving the treatment. Headaches and flu-like symptoms were the most common side effects, each affecting about 13% of patients. Importantly, no patients developed inhibitors, proteins that can reduce the treatment's effectiveness. Overall, AMT-061 has demonstrated a positive safety record based on past research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AMT-061 for Hemophilia B because it offers a potential one-time gene therapy solution. Unlike standard treatments that require frequent infusions of clotting factor IX (FIX), AMT-061 uses an adeno-associated virus (AAV5) to deliver a high-activity version of the FIX gene, known as the Padua variant, directly into the patient's cells. This approach aims to enable the patient's body to produce FIX on its own, reducing or even eliminating the need for regular FIX replacement therapy. The possibility of a single infusion providing long-lasting benefits is a game-changer for those living with Hemophilia B.

What evidence suggests that this treatment might be an effective treatment for Hemophilia B?

Research has shown that AMT-061, a gene therapy for hemophilia B, is promising. In this trial, participants will receive a single infusion of AMT-061, which previous studies have shown to increase levels of Factor IX (FIX), a protein needed for blood clotting. Specifically, FIX activity increased significantly, reducing the need for regular FIX treatments. Early results suggest that this therapy not only boosts FIX levels but also reduces bleeding episodes. Overall, these findings offer hope for a new way to manage hemophilia B. ^{1 2 3 6 7}

Who Is on the Research Team?

Steven Pipe, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for males over 18 with severe or moderately severe hemophilia B, who have had at least 150 days of prior treatment with factor IX protein. Participants must not have a history of gene therapy, active hepatitis B or C infections, uncontrolled HIV, or recent use of experimental drugs.

Inclusion Criteria

I am male.

I have severe or moderately severe hemophilia B and am on factor IX treatment.

I have been treated with factor IX for more than 150 days.

Exclusion Criteria

Receipt of an experimental agent within 60 days prior to screening

I have had gene therapy before.

I have Hepatitis B or C but it's under control with antiviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Period

Subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary

26 weeks

Treatment

Single infusion of AAV5-hFIXco-Padua (AMT-061) administered at baseline

Single dose

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Long-term Follow-up

Follow up and assess any adverse events reported for safety

5 years

What Are the Treatments Tested in This Trial?

Interventions

• AAV5-hFIXco-Padua
• Factor IX (FIX)

Trial Overview The HOPE-B trial tests AMT-061 (AAV5-hFIXco-Padua), a gene therapy aiming to treat hemophilia B. It's an open-label study where participants receive one dose intravenously to assess efficacy and safety.

How Is the Trial Designed?

Group I: AMT-061 Experimental Treatment 1 Intervention

Single infusion of AMT-061 Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After study drug administration (post study drug), subjects will be monitored for tolerance to the study drug and detection of potential immediate AEs at the clinical trial site for a few hours after dosing.

Group II: FIX replacement (Lead-in Period) Active Control 1 Intervention

During the lead-in phase, which lasted for a minimum of 26 weeks (i.e., ≥6 months), subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary.

Who Is Running the Clinical Trial?

UniQure Biopharma B.V.

Lead Sponsor

Trials

12

Recruited

260+

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03569891

Study Details | NCT03569891 | HOPE-B: Trial of AMT-061 ... This is an open-label, single-dose, multi-center, multinational trial to demonstrate the efficacy of AMT-061 and to further describe its safety profile.

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3348/423726/One-Year-Data-from-a-Phase-2b-Trial-of-AMT-061

One Year Data from a Phase 2b Trial of AMT-061 (AAV5 ... One Year Data from a Phase 2b Trial of AMT-061 (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11006816/

Hemophilia B and gene therapy: a new chapter with ... Both the peer-reviewed report and the FDA Summary Basis for Regulatory Action provide comprehensive summaries of the safety and efficacy data.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118612777

One Year Data from a Phase 2b Trial of AMT-061 (AAV5- ... Aims: Confirm that a single dose of AMT-061 will provide a minimum-therapeutic response of FIX activity 6-weeks post-dose in participants with ...

5. forbion.com forbion.com/news-insights/news/uniqure-announces-first-patient-treated-in-dose-confirmation-study-of-amt-061-in-patients-with-hemophilia-b/

uniQure First Patient Treated in Dose-Confirmation Study “As a one-time administered therapy, AMT-061 has the potential to transform the treatment paradigm for hemophilia B patients,” said Annette von ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118692304

Efficacy and Safety of Etranacogene Dezaparvovec (AAV5- ... In addition to these, the most frequent treatment-related AEs were headache (13.0%) and influenza-like illness (13.0%). No inhibitors to FIX ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2211644

Gene Therapy with Etranacogene Dezaparvovec for ... In our study, etranacogene dezaparvovec had a favorable safety and efficacy profile in men with severe or moderately severe hemophilia B, ...