What is the mechanism of action of this treatment?

Caplacizumab, an anti-von Willebrand Factor (vWF) nanobody, inhibits the interaction between vWF and platelets, preventing platelet adhesion and aggregation. This is crucial for Thrombotic Thrombocytopenic Purpura (TTP) patients as the disease involves the formation of small blood clots that can cause severe organ damage. By inhibiting vWF, caplacizumab reduces clot formation, improving patient outcomes. Other common treatments include plasma exchange to remove autoantibodies and immunosuppressive therapy to decrease antibody production, collectively aiming to manage the disease and prevent further clot formation.

What side effects are associated with this type of intervention?

Common treatments for Thrombotic Thrombocytopenic Purpura (TTP) include plasma exchange, immunosuppressive therapy, and Caplacizumab. Plasma exchange can cause side effects such as allergic reactions, infections, and blood clotting issues. Immunosuppressive therapy, often involving corticosteroids or drugs like rituximab, can lead to increased susceptibility to infections, hypertension, and diabetes. Caplacizumab, specifically, may cause bleeding-related complications, headaches, and fatigue. It is important to monitor patients closely for these side effects during treatment.

What prior FDA approvals exist?

Caplacizumab is an anti-von Willebrand Factor Nanobody that has been approved by the FDA for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). It works by inhibiting the interaction between von Willebrand factor and platelets, thus preventing platelet aggregation. Prior to Caplacizumab, the mainstay of treatment for TTP included plasma exchange and immunosuppressive therapy, such as corticosteroids and rituximab. These treatments aim to remove the autoantibodies and reduce their production, but Caplacizumab specifically targets the platelet aggregation process, providing a more targeted approach.

What other types of research exist?

Promising novel alternatives to Caplacizumab for TTP patients include investigational therapies like anti-TFPI (Tissue Factor Pathway Inhibitor) antibodies such as Concizumab, which have shown potential in clinical trials for hemophilia and may offer benefits in TTP by modulating coagulation pathways. Additionally, immunosuppressive therapies like Rituximab, which targets B-cells, have been used effectively in various autoimmune hematological disorders and may provide a viable alternative for TTP management.

← Back to Search

Monoclonal Antibodies

Caplacizumab + Immunosuppression for Thrombotic Thrombocytopenic Purpura (MAYARI Trial)

Phase 3

Waitlist Available

Research Sponsored by Sanofi

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or 2.

Be older than 18 years old

Must not have

Known other causes of thrombocytopenia including but not limited to: Clinical evidence of enteric infection with E. coli 0157 or related organism, atypical HUS, hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy, known or suspected sepsis, diagnosis of disseminated intravascular coagulation, congenital TTP (known at the time of study entry), clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia), inherited or acquired coagulation disorders, malignant arterial hypertension, participants requiring or expected to require invasive procedures immediately, those presenting with severe neurological or cardiac disease, clinical condition other than that associated with TTP, with life expectancy <6 months, known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, participants who were previously enrolled in this clinical study (study EFC16521), participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer, positive result on COVID test.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial tests a combination of caplacizumab and immunosuppressive therapy for adults aged 18-80 with a condition called iTTP. Caplacizumab helps stop harmful blood clots, and immunosuppressive therapy calms the immune system. The goal is to see if this treatment can help patients achieve remission. Caplacizumab is a new drug that has shown efficacy in clinical trials by normalizing platelet counts faster and protecting patients.

Who is the study for?

Adults aged 18-80 with immune-mediated thrombotic thrombocytopenic purpura (iTTP) can join this trial. They must have a specific score indicating iTTP severity, not be pregnant or breastfeeding, and agree to use contraception. Those with certain health conditions or high platelet counts are excluded.

What is being tested?

The study tests caplacizumab combined with immunosuppressive therapy in treating iTTP without using plasma exchange first. It's an open-label Phase 3 trial focusing on whether patients achieve remission within a maximum of 24 weeks.

What are the potential side effects?

Potential side effects may include reactions related to the immune system due to corticosteroids and anti-CD20 antibody, as well as those specific to caplacizumab which could involve bleeding issues or other infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have iTTP with a low to moderate risk score.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I don't have conditions like severe infections, bleeding disorders, or very high blood pressure, and haven't been in this study before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)

This trial's timeline: 3 weeks for screening, Varies for treatment, and overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).

Secondary study objectives

Proportion of participants achieving Clinical Response

Proportion of participants refractory to therapy

Proportion of participants with a clinical exacerbation of iTTP

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Caplacizumab & immunosuppressive therapy without 1st-line TPEExperimental Treatment3 Interventions

All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Caplacizumab

2011

Completed Phase 3

~350

Corticosteroids

2003

Completed Phase 4

~8270

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Caplacizumab, an anti-von Willebrand Factor (vWF) nanobody, inhibits the interaction between vWF and platelets, preventing platelet adhesion and aggregation. This is crucial for Thrombotic Thrombocytopenic Purpura (TTP) patients as the disease involves the formation of small blood clots that can cause severe organ damage. By inhibiting vWF, caplacizumab reduces clot formation, improving patient outcomes. Other common treatments include plasma exchange to remove autoantibodies and immunosuppressive therapy to decrease antibody production, collectively aiming to manage the disease and prevent further clot formation.