ITP Immune-Mediated Thrombocytopenia, Thrombotic Microangiopathies
Conditions
Keywords
iTTP, TMA, Thrombotic Microangiopathies, immune-mediated thrombotic thrombocytic purplura, thrombotic microangiopathy, TGD001
Brief summary
This is a Phase 1/2, prospective, adaptive design trial of TGD001 in participants with suspicion or clinical diagnosis of acute immune thrombotic thrombocytopenic purpura (iTTP) episodes and participants with suspicion or clinical diagnosis of an acute Thrombotic Microangiopathy (TMA) episode. The trial is an open-label, dose escalation and expansion basket trial.
Detailed description
In Part A, dose escalation of TGD001 is conducted in participants with suspicion or clinical diagnosis of immune thrombotic thrombocytopenic purpura (iTTP) in conjunction with their respective standard of care to identify a tolerated dose(s) with a pharmacological/clinical response to be evaluated in Part B. Once a recommended dose of TGD001 is established in Part A, the dose expansion/basket part of the trial will commence. In Part B, "basket" cohorts of participants with iTTP and other Thrombotic Microangiopathies (TMAs) will receive single or repeat doses of TGD001 in conjunction with their respective standard of care to determine the TGD001 dose and treatment regimen with clinical effect in reducing the initial thrombus burden. Baskets will include up to 20 participants each and may be combined based on emerging safety and efficacy findings. Baskets may be further expanded with the TGD001 dose(s) and regimen(s) that displayed the best clinical response as assessed by the Data Safety Management Committee up to a total of approximately 60 participants in Part B.
Interventions
DRUGTGD001
IV bolus administration
Sponsors
TargED Biopharmaceuticals B.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18 years old or older * Willing to sign an informed consent form * Willing to refrain from sexual intercourse or must use a contraceptive method that is highly effective for 90 days after the last dose of TGD001 * Symptomatic acute TMA episode * Accessible to follow-up Key
Exclusion criteria
* Diagnosis other than TMA, which could account for the findings of thrombocytopenia and hemolytic anemia * Diagnosis of Shiga-toxin induced HUS * Known bone marrow/graft failure * Diagnosis of ongoing severe, uncontrolled Graft versus Host Disease * Received therapeutic plasma exchange (PEX) within 7 days prior to screening * Use of an anticoagulant and/or thrombolytics * Active internal bleeding * Any major bleeding episode within the past 30 days, or diagnosis of chronic bleeding conditions * Known gastrointestinal ulcer * Severe, uncontrolled hypertension, renal impairment requiring dialysis, or liver impairment, or active infection indicated by sepsis * Life expectancy less than 3 months independent of TMA disorder * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment emergent adverse events (safety and tolerability of TGD001) | 90 days | Measurement of treatment emergent adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in lactate dehydrogenase (LDH) and other tissue damage markers | 90 days | Measurement of LDH and other tissue damage markers |
| Change from baseline in platelet count | 90 days | Measurements of platelet count from baseline |
| Time to resolution of the thrombotic episode | 90 days | Measurement of platelet count and LDH levels |
| Change from baseline of disease-related signs and symptoms using CTCAE v5.0 criteria | 90 days | Assessment or improvement of disease related signs and symptoms |
| Duration of ICU stay and hospitalization | 90 days | Number of days in the ICU and the number of days hospitalized |
| Occurrence of all-cause and disease-specific mortality | 90 days | All-cause and disease-specific mortality post-intervention |
| Peak plasma concentration (Cmax) of TGD001 | 90 days | Plasma concentrations and Cmax of TGD001 |
| Area under the plasma concentration versus time curve (AUC) of TGD001 | 90 days | Plasma concentrations of and AUC of TGD001 |
| Time to maximum TGD001 plasma concentration | 90 days | Plasma concentrations and Tmax of TGD001 |
| Plasma half-life (t1/2) of TGD001 | 90 days | Plasma concentrations and t1/2 of TGD001 |
| Number of participants with ADA | 90 days | Development of ADA |
Contacts
CONTACTMelinda Snyder
CONTACTBarbara van den Aarsen
STUDY_DIRECTORMarielle Klein Hesselink, MD
TargED
Outcome results
None listed