Clinical trial • Phase I/II • Haematology|Rare Disease

ADENO-ASSOCIATED VIRUS VECTOR SEROTYPE 8 CONTAINING THE HUMAN F9 GENE for Hemophilia B

Phase I/II trial of ADENO-ASSOCIATED VIRUS VECTOR SEROTYPE 8 CONTAINING THE HUMAN F9 GENE for Hemophilia B.

Overview

Trial Therapeutic Area
Haematology|Rare Disease
Trial Disease
Hemophilia B
Trial Stage
Phase I/II
Drug Modality
Gene therapy|mRNA

Key dates

Initial CTIS Submission Date
21-12-2023
First CTIS Authorization Date
22-04-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial in Germany, France, Italy and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, Part 1 includes dose confirmation cohorts to evaluate safety/tolerability and to establish a recommended dose for expansion (RDE); dose confirmation cohorts and selection of RDE imply dose-escalation/decision rules though specific escalation rules are not provided in the record.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
95
Trial Duration For Participant
728

Eligibility

Recruits 95 No vulnerable population selected; participants are adult males (≥18 years). Informed consent is obtained using subject information and informed consent forms (SIS-ICF_Main and variant ICFs listed among study documents). No assent procedures for minors are described..

Vulnerable Population
No vulnerable population selected; participants are adult males (≥18 years). Informed consent is obtained using subject information and informed consent forms (SIS-ICF_Main and variant ICFs listed among study documents). No assent procedures for minors are described.

Inclusion criteria

  • {"criterion_text":"- Male gender at birth and ≥18 years of age."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- NOTE: Other Inclusion Protocol Defined Criteria Apply."}

Exclusion criteria

  • {"criterion_text":"- History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions."}
  • {"criterion_text":"- NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply"}
  • {"criterion_text":"- Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening."}
  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- Any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy."}
  • {"criterion_text":"- Evidence of advanced liver fibrosis, as defined in the protocol."}
  • {"criterion_text":"- Evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit."}
  • {"criterion_text":"- History of arterial or venous thrombo-embolic events, as defined in the protocol."}
  • {"criterion_text":"- History of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids."}
  • {"criterion_text":"- 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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Part 1: Incidence and severity of treatment-emergent adverse events (TEAEs) up to 104 weeks.","definition_or_measurement_approach":"Safety: incidence and severity of TEAEs collected and recorded up to 104 weeks."}
  • {"endpoint_text":"- Part 1: Coagulation Factor IX (FIX) functional activity at day 29 measured using the chromogenic substrate assay.","definition_or_measurement_approach":"Measured using the chromogenic substrate assay at Day 29 to determine FIX functional activity."}
  • {"endpoint_text":"- Part 2A: Change from baseline in FIX functional activity in plasma at week 26 after REGN131-LNP1265 dosing at the recommended dose for expansion (RDE) measured using the chromogenic substrate assay.","definition_or_measurement_approach":"Change from baseline in plasma FIX functional activity measured at Week 26 using the chromogenic substrate assay."}
  • {"endpoint_text":"- Part 2A: Annualized bleeding rate (ABR) over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving RDE.","definition_or_measurement_approach":"ABR calculated over the 52-week period of sustained FIX functional activity (weeks 26–78 post-dosing)."}

Secondary endpoints

  • {"endpoint_text":"- Part 1: Change from baseline in FIX functional activity in plasma at 26 weeks after REGV131-LNP1265 dosing at the RDE, measured using the chromogenic substrate assay.","definition_or_measurement_approach":"Measured using the chromogenic substrate assay at Week 26; change from baseline."}
  • {"endpoint_text":"- Part 1: ABR over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.","definition_or_measurement_approach":"Annualized bleeding rate assessed over the 52-week sustained activity period (weeks 26–78)."}
  • {"endpoint_text":"- Part 1 and Part 2A: FIX functional activity in plasma over time during the study period using the chromogenic substrate assay up to 104 weeks.","definition_or_measurement_approach":"Serial plasma FIX functional activity measurements up to 104 weeks using the chromogenic substrate assay."}
  • {"endpoint_text":"- Part 1 and Part 2A: Annualized treated bleeding rate (tABR) over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.","definition_or_measurement_approach":"Annualized treated bleeding rate calculated over weeks 26–78 post-dosing."}
  • {"endpoint_text":"- Part 1 and Part 2A: Annualized utilization (IU/kg/year) of FIX replacement therapy over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.","definition_or_measurement_approach":"Annualized utilization of FIX replacement therapy (IU/kg/year) over weeks 26–78 post-dosing."}
  • {"endpoint_text":"- Part 1 and Part 2A: Remaining free of FIX replacement therapy among those receiving the RDE over 52 weeks following sustained FIX expression (weeks 26-78 post-REGV131-LNP1265 dosing).","definition_or_measurement_approach":"Proportion of participants not requiring FIX replacement therapy during weeks 26–78 post-dosing."}
  • {"endpoint_text":"- Part 1 and Part 2A: Remaining zero spontaneous bleeding events among those receiving the RDE over the 52 weeks of sustained FIX functional activity period (weeks 26-78 post-REGV131-LNP1265 dosing).","definition_or_measurement_approach":"Proportion of participants with zero spontaneous bleeding events during weeks 26–78 post-dosing."}
  • {"endpoint_text":"- Part 1 and Part 2A: Concentrations of REGV131 components up to 29 days.","definition_or_measurement_approach":"Concentration-time measurements of REGV131 components up to 29 days post-dose."}
  • {"endpoint_text":"- Part 1 and Part 2A: Concentrations of LNP1265 components up to 29 days.","definition_or_measurement_approach":"Concentration-time measurements of LNP1265 components up to 29 days post-dose."}
  • {"endpoint_text":"- Part 1 and Part 2A: Detection of antibodies to the F9 transgene product FIX protein up to 104 weeks.","definition_or_measurement_approach":"Assays to detect antibodies to the F9 transgene product (FIX) up to 104 weeks."}
  • {"endpoint_text":"- Part 1 and Part 2A: Detection of total binding antibodies (TAbs) to the adeno-associated virus 8 (AAV8) capsid proteins up to 104 weeks.","definition_or_measurement_approach":"Detection of total binding antibodies to AAV8 capsid proteins up to 104 weeks."}
  • {"endpoint_text":"- Part 1 and Part 2A: Detection of neutralizing antibodies/transduction inhibitors (NAb/TI) to the adeno-associated virus 8 (AAV8) capsid proteins up to 104 weeks.","definition_or_measurement_approach":"Detection of neutralizing antibodies/transduction inhibitors to AAV8 capsid proteins up to 104 weeks."}
  • {"endpoint_text":"- Part 1 and Part 2A: Detection of antibodies to LNP1265 up to 104 weeks.","definition_or_measurement_approach":"Detection of antibodies directed against LNP1265 up to 104 weeks."}
  • {"endpoint_text":"- Part 1 and Part 2A: Detection of antibodies to CRISPR-associated protein 9 (Cas9) protein up to 104 weeks.","definition_or_measurement_approach":"Detection of antibodies to Cas9 protein up to 104 weeks."}
  • {"endpoint_text":"- Part 1: Detection of vector DNA in blood, saliva, nasal secretions, semen, urine, and feces over time (Part 1 dose confirmation cohort only)","definition_or_measurement_approach":"PCR/NA detection of vector DNA in multiple matrices over time (Part 1 dose confirmation cohort only)."}
  • {"endpoint_text":"- Part 2A: Incidence and severity of TEAEs up to 104 weeks.","definition_or_measurement_approach":"Safety: incidence and severity of TEAEs collected and recorded up to 104 weeks for Part 2A."}
  • {"endpoint_text":"- Part 2A: Detection of vector DNA in relevant matrices based on data analysis of Part 1 Dose Confirmation Cohort up to 104 weeks.","definition_or_measurement_approach":"Detection of vector DNA in matrices selected based on Part 1 data analysis, up to 104 weeks."}

Recruitment

Digital Remote Recruitment
True, digital/remote methods include search engine advertising, banner ads, enhanced website, patient email outreach, and other online recruitment materials as listed in recruitment documents.
Planned Sample Size
95
Recruitment Window Months
59
Consent Approach
Informed consent is to be obtained from participants themselves (adult males ≥18). Subject information and informed consent forms (SIS-ICF_Main and multiple variants such as Prescreening, PGx, Liver Biopsy, Pregnant Partner, and translated ICFs) are provided among the study documents in multiple language versions; no assent procedures for minors are described.

Methods

  • Search engine advertising (SEA) campaigns (documented in recruitment materials).
  • Patient email outreach (Patient Email Layout documents).
  • Banner ads (Banner Ads documents).
  • Posters and leaflets (Poster Layout; Recruitment Leaflet Layout documents).
  • Enhanced study website (Enhanced Website / Website layout documents).
  • Study brochure and patient-facing infographics (Study brochure, Pt_Infographics, Pt infographics documents).
  • HCP-facing infographics and outreach (HCP infographics documents).
  • Video storyboard / video content for recruitment (Video Storyboard documents).
  • Subject recruitment performed via third-party agencies/CROs (e.g., Jumo Health, Clariness, ICON) as listed under third parties.

Geography

Total Number Of Sites
19
Total Number Of Participants
22

Germany

Earliest CTIS Part Ii Submission Date
22-03-2024
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
430
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Universitaetsklinikum Frankfurt AöR
Department Name
ZIM-Med II/ Institut für Transfusionsmedizin, Schwerpunkt Hämostaseologie/ Hämophiliezentrum
Contact Person Name
Wolfgang Miesbach
Contact Person Email
miesbach@em.uni-frankfurt.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Dept. of Haematology and Ocology
Contact Person Name
Florian Langer
Contact Person Email
langer@uke.de
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Dept. Ped. Hematology, Oncology and stem Cell Translantation
Contact Person Name
Sonja Kramer
Contact Person Email
Sonja1.kramer@ukr.de

France

Earliest CTIS Part Ii Submission Date
19-09-2024
Latest Decision Or Authorization Date
19-05-2025
Processing Time Days
242
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Adult Hematology Department
Contact Person Name
Laurent Frenzel
Contact Person Email
laurent.frenzel@aphp.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Hemostasis and Transfusion Department
Contact Person Name
Sophie Susen
Contact Person Email
sophie.susen@chu-lille.fr
Site Name
Hospices Civils De Lyon
Department Name
Clinical Hemostasis Unit
Contact Person Name
Yesim Dargaud
Contact Person Email
ydargaud@univ-lyon1.fr

Italy

Earliest CTIS Part Ii Submission Date
29-08-2024
Latest Decision Or Authorization Date
19-05-2025
Processing Time Days
263
Number Of Sites
5
Number Of Participants
4

Sites

Site Name
Azienda Unita Locale Socio Sanitaria N 8 Berica
Department Name
UOC Hematology
Contact Person Name
Ilaria Nichele
Site Name
Humanitas Mirasole S.p.A.
Department Name
Center of Thrombosis and Hemorrhagic Disease
Contact Person Name
Maria Elisa Mancuso
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
S.C. MEDICINA EMOSTASI E TROMBOSI, Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"
Contact Person Name
Flora Peyvandi
Site Name
Careggi University Hospital
Department Name
Oncology
Contact Person Name
Giancarlo Castaman
Site Name
IRCCS Istituto Giannina Gaslini
Department Name
Hemostasis and Thrombosis Center
Contact Person Name
Laura Banov
Contact Person Email
lbanov@gaslini.org

Spain

Earliest CTIS Part Ii Submission Date
23-08-2024
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
276
Number Of Sites
8
Number Of Participants
6

Sites

Site Name
Hospital Universitario Central De Asturias
Department Name
Hematology
Contact Person Name
Maria Inmaculada Soto Ortega
Contact Person Email
inmaculada.soto@sespa.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematology
Contact Person Name
Olga Benitez Hidalgo
Contact Person Email
obenitez@vhebron.net
Site Name
Hospital Universitario Miguel Servet
Department Name
Hematology
Contact Person Name
Jose Manuel Calvo Villas
Contact Person Email
jmcvillas@hotmail.com
Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Victor Manuel Jimenez Yuste
Contact Person Email
vjyuste.ensayos@gmail.com
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Hematology
Contact Person Name
Ana Rosa Cid Haro
Contact Person Email
cid_ana@gva.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Contact Person Name
Ramiro José Nuñez Vazquez
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Hematology
Contact Person Name
Faustino Garcia Candel
Contact Person Email
fausgarcia@icloud.com
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Hematology
Contact Person Name
Maria del Carmen Gomez del Castillo

Sponsor

Primary sponsor

Full Name
Regeneron Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Contract Research Organization

Third parties

  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Contract Research Organization","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Central Lab","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Subject Recruitment","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"patient reimbursement and travel arrangements","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"patient recruitment","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"eCOA, PRO's and eDiary","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translations","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"Speciality Lab","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Clinical Supply","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Qualified Person Duties","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"Unspecified (code 6 in record)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"IDMC","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
REGV131
Active Substance
ADENO-ASSOCIATED VIRUS VECTOR SEROTYPE 8 CONTAINING THE HUMAN F9 GENE
Modality
Gene therapy
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
prodAuthStatus:1
Frequency
Single IV administration
Investigational Product Name
LNP1265
Active Substance
MESSENGER RNA ENCODING CAS9; SINGLE GUIDE RNA CONTAINING A SEQUENCE COMPLEMENTARY TO HUMAN ALB LOCUS GENE, INTRON 1, TARGET REGION
Modality
mRNA
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
prodAuthStatus:1
Frequency
Single IV administration
Combination Treatment
Yes

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