A Two-Part Open-Label Study of REGV131-LNP1265, A CRISPR/CAS9-Based Coagulation Factor IX Gene Insertion Therapy in Participants with Hemophilia B
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase I-II
PATOLOGÍA
Coagulopatías hemorrágicas, Linfoma no Hodgkin, --> Otros, Terapia celular y T-CARs, Linfoma
CENTRO INVESTIGADOR
H.U. La Paz
INVESTIGADOR PRINCIPAL
Victor Manuel Jimenez Yuste
FECHA DE APERTURA
Septiembre, 2024
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Male gender at birth and 18 years of age.
Confirmed diagnosis of severe or moderately severe hemophilia B with medical history of FIX functional activity (2% or <0.02 IU/mL) or documented genotype known to produce severe hemophilia B.
Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol.
Participation in the lead-in period of this interventional study OR a separate lead-in study (R0000-HEMB-2187 [NCT05568459]) for at least 6 months for ABR data while taking FIX prophylaxis, as defined in the protocol.
NOTE: Other Inclusion Protocol Defined Criteria Apply.
Confirmed diagnosis of severe or moderately severe hemophilia B with medical history of FIX functional activity (2% or <0.02 IU/mL) or documented genotype known to produce severe hemophilia B.
Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol.
Participation in the lead-in period of this interventional study OR a separate lead-in study (R0000-HEMB-2187 [NCT05568459]) for at least 6 months for ABR data while taking FIX prophylaxis, as defined in the protocol.
NOTE: Other Inclusion Protocol Defined Criteria Apply.
CRITERIOS DE EXCLUSIÓN
History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions.
NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply
Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening.
Detectable pre-existing antibodies to the adeno-associated virus serotype 8 (AAV8) capsid; as measured by enzyme-linked immunosorbent assay (ELISA) at prescreening (or final lead-in visit [L-Final], if applicable)
Any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy.
Evidence of advanced liver fibrosis, as defined in the protocol.
Evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit.
History of arterial or venous thrombo-embolic events, as defined in the protocol.
History of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids.
Previously received any AAV gene-based therapy or intends to receive approved or investigational AAV-based gene therapy other than REGV131-LNP1265 during the study period.
NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply
Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening.
Detectable pre-existing antibodies to the adeno-associated virus serotype 8 (AAV8) capsid; as measured by enzyme-linked immunosorbent assay (ELISA) at prescreening (or final lead-in visit [L-Final], if applicable)
Any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy.
Evidence of advanced liver fibrosis, as defined in the protocol.
Evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit.
History of arterial or venous thrombo-embolic events, as defined in the protocol.
History of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids.
Previously received any AAV gene-based therapy or intends to receive approved or investigational AAV-based gene therapy other than REGV131-LNP1265 during the study period.
DESCRIPCIÓN
Part 1: To evaluate the safety and tolerability of a single IV administration of REGV131-LNP1265 in participants with hemophilia B. To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B to establish the recommended dose for further development Part 2A: To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B receiving the recommended dose for expansion (RDE). To assess the bleeding event rate (all bleeding events) following a single IV administration of REGV131-LNP1265 at the RDE Long-term Follow Up (LTFU) Period: To evaluate the long-term safety of a single IV administration of REGV131-LNP1265 in participants with hemophilia B
PALABRAS CLAVE
complement inhibitor, crispr, diffuse large b-cell lymphoma (dlbcl) activated b-cell type, diffuse large b-cell lymphoma (dlbcl) germinal center b-cell type, diffuse large b-cell lymphoma (dlbcl), non germinal center b-cell type, gene therapy, hemophilia, non germinal center b-cell type
