NXT007 for Hemophilia A

Recruiting at 19 trial locations

Overseen By Reference Study ID Number: WP44714 https://forpatients.roche.com/

Age: < 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must be taking: Recombinant activated factor VII

Must not be taking: QT-prolonging medications

Disqualifiers: Bleeding disorders, Thromboembolic disease, Diabetes, Malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable duration based on dose escalation

60 Participants Needed

Trial Summary

What is the purpose of this trial?

WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter trial consisting of two parts: * Part 1 is a multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or moderate hemophilia A with or without factor VIII (FVIII) inhibitors. * Part 2 is a multiple-dose study in pediatric male participants with severe or moderate hemophilia A with or without FVIII inhibitors. The overall aim of the study is to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of NXT007.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using certain investigational drugs or medications that prolong the QT interval, you may need to stop those before participating.

How is the drug NXT007 different from other treatments for hemophilia A?

NXT007 is unique because it may offer a novel approach to treating hemophilia A by potentially targeting different pathways or mechanisms compared to traditional factor VIII replacement therapies. While existing treatments focus on replacing the missing factor VIII, NXT007 might work differently, possibly involving innovative methods like targeting tissue factor pathway inhibitor (TFPI) to enhance clot formation. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for males with severe or moderate Hemophilia A, weighing over 40 kg. They must have a history of bleeding episodes and be willing to follow the study's procedures. Participants can't join if they have poor kidney, liver, or blood function.

Inclusion Criteria

My kidney function is within the required range.

I weigh at least 40 kilograms.

Historic local FVIII inhibitor test results must be available during screening to confirm any previous inhibitor history and current status

Exclusion Criteria

My close family members had heart or brain blood vessel diseases early.

I have a history of significant heart issues noted on an ECG.

I have not taken any experimental drugs or had gene therapy recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple ascending doses of NXT007 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy

Variable duration based on dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including vital signs and ECG abnormalities

Up to 7.5 years

Treatment Details

Interventions

• NXT007

Trial Overview The trial tests NXT007 in adults and teens with Hemophilia A to see how safe it is and how well it works at different doses. It's an early-stage (Phase I/II) global study where everyone gets the drug; there's no comparison group.

Participant Groups

Group I: Part 2: Cohort A - NXT007 Experimental Treatment 1 Intervention

Group II: Part 1: Cohort 5 - NXT007 Dose Level 5 (High) Experimental Treatment 1 Intervention

Group III: Part 1: Cohort 4 - NXT007 Dose Level 4 Experimental Treatment 1 Intervention

Group IV: Part 1: Cohort 3 - NXT007 Dose Level 3 Experimental Treatment 1 Intervention

Group V: Part 1: Cohort 2 - NXT007 Dose Level 2 Experimental Treatment 1 Intervention

Group VI: Part 1: Cohort 1 - NXT007 Dose Level 1 (Low) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

N9-GP, a new recombinant factor IX treatment for hemophilia B, demonstrated a significantly prolonged half-life of 93 hours, which is five times longer than previous FIX products, suggesting it could reduce the frequency of dosing.

The treatment was well-tolerated in a trial with 16 patients, with no development of inhibitors and only one case of transient hypersensitivity, indicating a favorable safety profile for N9-GP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Negrier, C., Knobe, K., Tiede, A., et al.[2022]

Blocking tissue factor pathway inhibitor (TFPI) may offer a new treatment strategy for hemophilia by enhancing clot formation, as shown in both in vitro and rabbit hemophilia models.

The monoclonal antibody mAb 2021, which targets the Kunitz-type protease inhibitor (KPI) 2 domain of TFPI, has demonstrated promising pro-hemostatic effects and is currently undergoing preclinical and clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemostatic properties of a TFPI antibody. Petersen, LC.[2019]

A 9-month-old boy with hemophilia B developed inhibitors and an allergic reaction to factor IX after treatment, leading to a switch in therapy.

Prophylactic treatment with pdFVIIa/factor X successfully prevented life-threatening bleeding for over 2 years, suggesting it may be an effective option for hemophilia B patients with inhibitors and allergic reactions to FIX concentrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis Using a Mixture of Plasma-Derived Activated Factor VII and Factor X (pdFVIIa/FX) in a Patient with Hemophilia B Complicated by Inhibitors and Allergy to Factor IX Concentrates: A Case Report. Uchida, E., Komori, K., Kurata, T., et al.[2021]

N8-GP, an extended half-life recombinant factor VIII, effectively maintains FVIII levels above 1 IU/dL in both adults and children with severe hemophilia A during prophylaxis, with dosing schedules of every 4 days for adults/adolescents and twice weekly for children.

The pharmacokinetic study involving 69 patients showed that N8-GP's half-life is positively correlated with von Willebrand factor levels in adults/adolescents, suggesting that this relationship may influence dosing strategies for optimal treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A. Chowdary, P., Carcao, M., Holme, PA., et al.[2023]

Turoctocog alfa (NovoEight®) is a third-generation recombinant factor VIII concentrate that has shown excellent efficacy and safety in both prophylactic and on-demand treatment for patients with severe hemophilia A, based on clinical trials.

This treatment not only effectively prevents bleeding episodes but also demonstrates high hemostatic activity during surgical procedures, with ongoing post-marketing studies expected to provide further insights into its long-term benefits and the incidence of inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the safety and efficacy of turoctocog alfa for hemophilia A. Boban, A., Hermans, C.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Hemostatic properties of a TFPI antibody. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prophylaxis Using a Mixture of Plasma-Derived Activated Factor VII and Factor X (pdFVIIa/FX) in a Patient with Hemophilia B Complicated by Inhibitors and Allergy to Factor IX Concentrates: A Case Report. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A. [2023]

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of the safety and efficacy of turoctocog alfa for hemophilia A. [2021]