HMB-001 for Thrombasthenia

Recruiting at 18 trial locations

Overseen By Andrew Law

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hemab ApS

Must not be taking: Estrogen medications

Disqualifiers: Severe infection, Thrombosis, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

57 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia. The main questions it aims to answer are: * Parts A, B, and C: To determine the safety and tolerability of HMB-001 * Part A: To establish the dose level(s) and dosing interval(s) of HMB-001 to be investigated in Parts B and C * Parts B and C: To estimate the ability of HMB-001 to prevent the number and severity of bleeds Part A will assess differing singular doses of HMB-001 in small groups of participants. The dose administered to a newly enrolled participant (or groups of participants) may only increase if analysis of data from previous dosing shows it is safe to do so. The planned duration of participation in Part A is approximately 6 months, which consists of a Screening Period, an optional Run-in Observation Period, and a follow-up period of 8 weeks. Part B is similar to Part A as it involves testing different dose levels of HMB-001 in small groups of participants. However, in Part B, HMB-001 is given multiple times over a 3-month period, either weekly, every 2 weeks, or every 4 weeks. Part B consists of a Screening Period, a Run-in Observation Period, a 3-month Treatment Period, and a Safety Follow-up following the last dose of HMB-001. Part C is open to participants from Part B and consists of approximately a 9-month Treatment Period and a Safety Follow-up following the last dose of HMB-001.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, women using estrogen-containing medications must stop 8 weeks before and after the study drug. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, women using estrogen-containing medications must stop 8 weeks before and after the study drug. It's best to discuss your specific medications with the trial team.

What data supports the idea that HMB-001 for Thrombasthenia is an effective treatment?

The available research does not provide specific data on the effectiveness of HMB-001 for Thrombasthenia. The studies mentioned focus on other conditions and treatments, such as venous thromboembolism and chronic thromboembolic pulmonary hypertension, but do not include information on HMB-001 for Thrombasthenia. Therefore, there is no direct evidence from the provided research to support the effectiveness of HMB-001 for this condition. ^{1 2 3 4 5}

What safety data is available for HMB-001 in treating Thrombasthenia?

The provided research does not contain any safety data specifically for HMB-001 or its evaluation in treating Thrombasthenia. The studies focus on other anticoagulants like dabigatran, rivaroxaban, apixaban, and edoxaban, which are not related to HMB-001. ^{6 7 8 9 10}

Is the treatment HMB-001 a promising treatment for Thrombasthenia?

The information provided does not mention HMB-001 or its effectiveness for Thrombasthenia. Therefore, we cannot determine if HMB-001 is a promising treatment for this condition based on the given data. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for individuals with Glanzmann Thrombasthenia, a rare bleeding disorder. Participants should be willing to undergo various tests and follow-ups. Specific details on who can or cannot participate are not provided here, but typically include factors like age, health status, and the severity of their condition.

Inclusion Criteria

I have Glanzmann thrombasthenia with confirmed abnormal platelet function and a specific receptor deficiency.

Vital signs within specified ranges at Screening

My organ functions meet the required health standards.

Exclusion Criteria

History of clinically significant hypersensitivity associated with monoclonal antibody therapies

Positive test for certain infections or conditions

Received investigational medication in another clinical study within 5 half-lives before administration of study drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Observation

Optional observation period before treatment to monitor baseline conditions

2-4 weeks

Treatment Part A

Participants receive differing singular doses of HMB-001 to assess safety and tolerability

6 months

Follow-up Part A

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Part B

Participants receive multiple doses of HMB-001 over a 3-month period to assess safety and efficacy

3 months

Safety Follow-up Part B

Participants are monitored for safety following the last dose of HMB-001

Treatment Part C

Participants from Part B receive HMB-001 over a 9-month period to further assess safety and efficacy

9 months

Safety Follow-up Part C

Participants are monitored for safety following the last dose of HMB-001

Treatment Details

Interventions

• HMB-001

Trial Overview The study is testing HMB-001's safety, how well it's tolerated by patients' bodies (tolerability), how it moves through and affects the body (pharmacokinetics/pharmacodynamics), and its effectiveness in preventing bleeds in Glanzmann Thrombasthenia patients. It has three parts: Part A tests single doses; Part B multiple doses over 3 months; Part C continues treatment from Part B for about 9 months.

Participant Groups

Group I: Single or Multiple ascending dose of HMB-001 Experimental Treatment 1 Intervention

Open-label, single or multiple ascending dose of HMB-001

Who Is Running the Clinical Trial?

Hemab ApS

Lead Sponsor

Trials

6

Recruited

1,100+

Findings from Research

In a review of 16 studies involving over 22,000 patients, standard-intensity vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) were found to be more effective than aspirin in preventing recurrent venous thromboembolism (VTE) beyond 3 months.

While VKAs showed a higher risk of major bleeding, they were also associated with a lower risk of all-cause mortality compared to placebo, suggesting that despite safety concerns, VKAs may offer significant benefits in long-term VTE management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended treatment of venous thromboembolism: a systematic review and network meta-analysis. Wang, KL., van Es, N., Cameron, C., et al.[2019]

The review covers various drug therapies aimed at treating venous thromboembolism, which is a condition where blood clots form in veins, highlighting the importance of effective anticoagulant treatments.

It also discusses strategies for managing hypertension and promoting plaque regression, as well as methods to prevent stent thrombosis, which is the formation of clots in stents used to open blocked arteries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European society of cardiology congress 2013. Alexander, W.[2021]

The study found that using new oral anticoagulants (NOACs) like rivaroxaban, apixaban, and edoxaban resulted in lower rates of major bleeding and recurrent venous thromboembolism (VTE) compared to standard therapy, indicating improved safety and efficacy.

Overall medical costs were significantly reduced when using NOACs instead of standard therapy, with apixaban showing the greatest cost reduction, suggesting that these medications not only improve patient outcomes but also lower healthcare expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of medical costs associated with use of new oral anticoagulants compared with standard therapy among venous thromboembolism patients. Amin, A., Jing, Y., Trocio, J., et al.[2022]

Endovascular treatment using self-expanding nitinol stents for patients with iliofemoral venous obstruction showed a primary patency rate of 79% at 12 months, indicating effective long-term vessel openness, especially in non-thrombotic iliac vein lesions (NIVL).

A significant majority of patients (67%) experienced clinical improvement, as measured by the Villalta score, suggesting that this treatment not only maintains venous patency but also enhances patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular treatment of post-thrombotic and non-thrombotic iliofemoral venous outflow obstructions with self-expanding nitinol stents. Stuck, AK., Reich, T., Engelberger, RP., et al.[2018]

Pulmonary endarterectomy has significantly improved outcomes for patients with chronic thromboembolic disease by reducing morbidity and mortality through the removal of organized thrombus.

Despite advancements in treatment, the underlying causes and mechanisms of chronic thromboembolic disease are still not well understood, highlighting a gap between clinical progress and basic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic thromboembolic pulmonary hypertension: time for research in pathophysiology to catch up with developments in treatment. Toshner, M., Pepke-Zaba, J.[2021]

In a study involving 5142 patients, rivaroxaban demonstrated a lower incidence of major bleeding (0.8%) compared to standard anticoagulation therapy (2.1%), suggesting it may be a safer option for treating deep-vein thrombosis.

Rivaroxaban also showed comparable effectiveness in preventing recurrent venous thromboembolism (1.4% vs. 2.3% for standard therapy), indicating it is an effective alternative in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Ageno, W., Mantovani, LG., Haas, S., et al.[2022]

In a study of 499 patients with acute symptomatic venous thromboembolism (VTE) treated with rivaroxaban, the major and clinically relevant bleeding rate was lower (5.4%) compared to those treated with vitamin K antagonists (VKAs) and heparin/fondaparinux, indicating rivaroxaban's safety profile is favorable.

Rivaroxaban also demonstrated a significantly lower rate of recurrent VTE (1.4%) compared to VKAs (3.1%) and heparin/fondaparinux (11.6%), suggesting it is an effective treatment option for preventing VTE recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes. Gaertner, S., Cordeanu, EM., Nouri, S., et al.[2017]

New oral anticoagulants (NOAs) like dabigatran, rivaroxaban, apixaban, and edoxaban are as effective as vitamin K antagonists (VKAs) in preventing recurrent venous thromboembolism (VTE), with a risk ratio of 0.89 based on a review of 10 randomized controlled trials involving nearly 38,000 patients.

NOAs have a significantly lower incidence of major bleeding compared to VKAs (1.08% vs. 1.73%), leading to a net clinical benefit favoring NOAs, with a risk ratio of 0.79, indicating they are a safer option for VTE management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Editor's Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Kakkos, SK., Kirkilesis, GI., Tsolakis, IA.[2018]

New oral anticoagulants like rivaroxaban, apixaban, and dabigatran have been developed to address the limitations of traditional therapies, showing effectiveness in preventing thromboembolic diseases with predictable pharmacokinetics and safety profiles.

These agents have undergone extensive phase 3 testing and are approved for various uses, such as stroke prevention in atrial fibrillation and VTE prevention after major orthopedic surgery, indicating their growing role in modern anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving toward a more ideal anticoagulant: the oral direct thrombin and factor Xa inhibitors. King, CS., Holley, AB., Moores, LK.[2017]

Dabigatran etexilate shows similar relationships between plasma concentrations and coagulation parameters (aPTT, dTT, ECT) in both children and adults, indicating consistent efficacy across age groups.

In children under 6 months, baseline aPTT and ECT values were slightly higher than in older children, but overall, developmental changes in the hemostatic system do not significantly affect the response to dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials. Mitchell, LG., Röshammar, D., Huang, F., et al.[2022]

A new thrombus-specific ultrasound contrast agent, MRX-408, was developed using a targeted lipid blend that effectively binds to blood clots, enhancing the detection of deep venous thrombosis.

In vitro studies demonstrated that MRX-408 microbubbles are stable and significantly improve ultrasound imaging of blood clots compared to nontargeted microbubbles, suggesting potential for better differentiation between new and old thrombosis in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro studies of a new thrombus-specific ultrasound contrast agent. Unger, EC., McCreery, TP., Sweitzer, RH., et al.[2019]

MRX-408, a thrombus-specific ultrasound contrast agent, effectively binds to blood clots rich in activated platelets, enhancing their visibility during ultrasound imaging.

In preliminary studies, MRX-408 improved clot lysis efficiency to 34% when combined with ultrasound treatment, demonstrating its potential to facilitate sonothrombolysis compared to saline, which showed no lysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding and lysing of blood clots using MRX-408. Wu, Y., Unger, EC., McCreery, TP., et al.[2019]

The study developed a new ultrasound contrast agent using perfluorobutane-filled microbubbles conjugated with thrombin-sensitive peptides, which can effectively detect acute deep vein thrombosis (DVT).

When tested, the contrast agent retained 91.7% of its signal in the presence of thrombin, indicating its effectiveness in identifying acute thrombosis, while only 16.7% of the signal was retained when a thrombin inhibitor was present, demonstrating the specificity of the agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis. Lux, J., Vezeridis, AM., Hoyt, K., et al.[2022]

The newly developed nanomedicine, FTIAN, effectively targets and images obstructed blood vessels while also inhibiting thrombus formation, showcasing its dual role as a diagnostic and therapeutic agent.

In mouse models, FTIAN demonstrated significant antithrombotic effects by suppressing thrombus formation when combined with the antiplatelet drug tirofiban, indicating its potential for treating obstructive thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrin-Targeted and H2O2-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels. Kang, C., Gwon, S., Song, C., et al.[2019]

In patients undergoing intrauterine hypertonic saline infusion, levels of Fibrinopeptide A (FPA) rose quickly after treatment, indicating immediate thrombin activity that cleaves FPA from fibrinogen, while TIFPB levels peaked at 4 hours, suggesting ongoing fibrin degradation processes.

The study reveals a complex sequence of proteolysis where plasmin acts on fibrin I to regulate the formation of fibrin II, highlighting the dynamic interactions between coagulation and fibrinolysis during and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline. Nossel, HL., Wasser, J., Kaplan, KL., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Extended treatment of venous thromboembolism: a systematic review and network meta-analysis. [2019]

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

European society of cardiology congress 2013. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of medical costs associated with use of new oral anticoagulants compared with standard therapy among venous thromboembolism patients. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Endovascular treatment of post-thrombotic and non-thrombotic iliofemoral venous outflow obstructions with self-expanding nitinol stents. [2018]

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

Chronic thromboembolic pulmonary hypertension: time for research in pathophysiology to catch up with developments in treatment. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Editor's Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. [2018]

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

Moving toward a more ideal anticoagulant: the oral direct thrombin and factor Xa inhibitors. [2017]

10. Germany pubmed.ncbi.nlm.nih.gov

Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials. [2022]

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

In vitro studies of a new thrombus-specific ultrasound contrast agent. [2019]

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

Binding and lysing of blood clots using MRX-408. [2019]

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

Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis. [2022]

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

Fibrin-Targeted and H2O2-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels. [2019]

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

Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline. [2018]