TGD001-behandling i trombotsk mikroangiopati
En adaptiv dose-escalering og ekspansjonskurvstudie for å utforske sikkerheten, farmakologien og klinisk aktivitet av TGD001 i immunmediert trombotisk trombocytopenisk purpura (iTTP) og andre trombotiske 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.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Melinda Snyder
- Telefonnummer: 1 617 233 4057
- E-post: melinda.snyder@targedbio.com
Studer Kontakt Backup
- Navn: Barbara van den Aarsen
- Telefonnummer: 31620161487
- E-post: barbara.van.den.aarsen@Targedbio.com
Studiesteder
-
-
-
Valencia, Spania
- Rekruttering
- La Fe University and Polytechnic Hospital
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Dose Level 1
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Dose Level 2
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Dose Level 3
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Dose Level 4
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Basket 1
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Basket 2
TGD001 IV bolus administration |
IV bolus administration |
|
Eksperimentell: Basket 3
TGD001 IV bolus administration |
IV bolus administration |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Incidence of treatment emergent adverse events (safety and tolerability of TGD001)
Tidsramme: 90 days
|
Measurement of treatment emergent adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) criteria |
90 days
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change from baseline in lactate dehydrogenase (LDH) and other tissue damage markers
Tidsramme: 90 days
|
Measurement of LDH and other tissue damage markers |
90 days
|
|
Change from baseline in platelet count
Tidsramme: 90 days
|
Measurements of platelet count from baseline |
90 days
|
|
Time to resolution of the thrombotic episode
Tidsramme: 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
Tidsramme: 90 days
|
Assessment or improvement of disease related signs and symptoms |
90 days
|
|
Duration of ICU stay and hospitalization
Tidsramme: 90 days
|
Number of days in the ICU and the number of days hospitalized |
90 days
|
|
Occurrence of all-cause and disease-specific mortality
Tidsramme: 90 days
|
All-cause and disease-specific mortality post-intervention |
90 days
|
|
Peak plasma concentration (Cmax) of TGD001
Tidsramme: 90 days
|
Plasma concentrations and Cmax of TGD001 |
90 days
|
|
Area under the plasma concentration versus time curve (AUC) of TGD001
Tidsramme: 90 days
|
Plasma concentrations of and AUC of TGD001 |
90 days
|
|
Time to maximum TGD001 plasma concentration
Tidsramme: 90 days
|
Plasma concentrations and Tmax of TGD001 |
90 days
|
|
Plasma half-life (t1/2) of TGD001
Tidsramme: 90 days
|
Plasma concentrations and t1/2 of TGD001 |
90 days
|
|
Number of participants with ADA
Tidsramme: 90 days
|
Development of ADA |
90 days
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Marielle Klein Hesselink, MD, TargED
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Cytopeni
- Patologiske prosesser
- Autoimmune sykdommer
- Sykdommer i immunsystemet
- Blødning
- Hudmanifestasjoner
- Hematologiske sykdommer
- Blodkoagulasjonsforstyrrelser
- Hemoragiske lidelser
- Blodplateforstyrrelser
- Purpura, trombocytopenisk
- Purpura
- Trombocytopeni
- Patologiske tilstander, tegn og symptomer
- Tegn og symptomer
- Hemic og lymfatiske sykdommer
- Purpura, trombocytopenisk, idiopatisk
- Trombotiske mikroangiopatier
Andre studie-ID-numre
- TG1-CL-301
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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.
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