TGD001-behandling vid trombocytopenisk mikroangiopati
En adaptiv doseskalering och expansionskorgsstudie för att utforska säkerheten, farmakologin och den kliniska aktiviteten hos TGD001 vid immunmedierad trombotisk trombocytopen purpura (iTTP) och andra trombotiska mikroangiopatier
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.
Studieöversikt
Status
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 2
- Fas 1
Kontakter och platser
Studiekontakt
- Namn: Melinda Snyder
- Telefonnummer: 1 617 233 4057
- E-post: melinda.snyder@targedbio.com
Studera Kontakt Backup
- Namn: Barbara van den Aarsen
- Telefonnummer: 31620161487
- E-post: barbara.van.den.aarsen@Targedbio.com
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Dose Level 1
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Dose Level 2
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Dose Level 3
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Dose Level 4
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Basket 1
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Basket 2
TGD001 IV bolus administration |
IV bolus administration |
|
Experimentell: Basket 3
TGD001 IV bolus administration |
IV bolus administration |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Incidence of treatment emergent adverse events (safety and tolerability of TGD001)
Tidsram: 90 days
|
Measurement of treatment emergent adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) criteria |
90 days
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Change from baseline in lactate dehydrogenase (LDH) and other tissue damage markers
Tidsram: 90 days
|
Measurement of LDH and other tissue damage markers |
90 days
|
|
Change from baseline in platelet count
Tidsram: 90 days
|
Measurements of platelet count from baseline |
90 days
|
|
Time to resolution of the thrombotic episode
Tidsram: 90 days
|
Measurement of platelet count and LDH levels |
90 days
|
|
Change from baseline of disease-related signs and symptoms using CTCAE v5.0 criteria
Tidsram: 90 days
|
Assessment or improvement of disease related signs and symptoms |
90 days
|
|
Duration of ICU stay and hospitalization
Tidsram: 90 days
|
Number of days in the ICU and the number of days hospitalized |
90 days
|
|
Occurrence of all-cause and disease-specific mortality
Tidsram: 90 days
|
All-cause and disease-specific mortality post-intervention |
90 days
|
|
Peak plasma concentration (Cmax) of TGD001
Tidsram: 90 days
|
Plasma concentrations and Cmax of TGD001 |
90 days
|
|
Area under the plasma concentration versus time curve (AUC) of TGD001
Tidsram: 90 days
|
Plasma concentrations of and AUC of TGD001 |
90 days
|
|
Time to maximum TGD001 plasma concentration
Tidsram: 90 days
|
Plasma concentrations and Tmax of TGD001 |
90 days
|
|
Plasma half-life (t1/2) of TGD001
Tidsram: 90 days
|
Plasma concentrations and t1/2 of TGD001 |
90 days
|
|
Number of participants with ADA
Tidsram: 90 days
|
Development of ADA |
90 days
|
Samarbetspartners och utredare
Sponsor
Utredare
- Studierektor: Marielle Klein Hesselink, MD, TargED
Studieavstämningsdatum
Studera stora datum
Studiestart (Beräknad)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Cytopeni
- Patologiska processer
- Autoimmuna sjukdomar
- Immunsystemets sjukdomar
- Blödning
- Hudmanifestationer
- Hematologiska sjukdomar
- Blodkoagulationsstörningar
- Hemorragiska störningar
- Blodplättssjukdomar
- Purpura, trombocytopenisk
- Purpura
- Trombocytopeni
- Patologiska tillstånd, tecken och symtom
- Tecken och symtom
- Hemiska och lymfsjukdomar
- Purpura, Trombocytopenisk, Idiopatisk
- Trombotiska mikroangiopatier
Andra studie-ID-nummer
- TG1-CL-301
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
IPD will not be shared due to the small sample size in this early phase clinical trial in a rare patient population. Such a small sample size would pose a significant risk of re-identification of study participants.
Läkemedels- och apparatinformation, studiedokument
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