Clinical trial • Phase III • Haematology|Rare Disease

LUSPATERCEPT for Myelodysplastic syndrome|Lower-risk myelodysplastic syndrome

Phase III trial of LUSPATERCEPT for Myelodysplastic syndrome|Lower-risk myelodysplastic syndrome. open-label, none/not specified-controlled.

Overview

Trial Therapeutic Area
Haematology|Rare Disease
Trial Disease
Myelodysplastic syndrome|Lower-risk myelodysplastic syndrome
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
06-10-2023
First CTIS Authorization Date
13-02-2024

Trial design

open-label, none/not specified-controlled Phase III trial in Belgium, Czechia, France and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
72
Trial Duration For Participant
730

Eligibility

Recruits 72 The record indicates isVulnerablePopulationSelected = true. All participants must be 18 years or older (consent provided by participant). Country-specific subject information and informed consent forms (ICFs) are provided (multiple languages and versions). There are specific ICF templates for pregnant partner and newborn (e.g. PP_Newborn ICF in Belgium) and optional / future research/sample collection ICFs, indicating tailored consent documents for specific situations. No assent for minors is applicable because minimum age is 18..

Pregnancy Exclusion
pregnant, plan to get pregnant or breastfeeding
Vulnerable Population
The record indicates isVulnerablePopulationSelected = true. All participants must be 18 years or older (consent provided by participant). Country-specific subject information and informed consent forms (ICFs) are provided (multiple languages and versions). There are specific ICF templates for pregnant partner and newborn (e.g. PP_Newborn ICF in Belgium) and optional / future research/sample collection ICFs, indicating tailored consent documents for specific situations. No assent for minors is applicable because minimum age is 18.

Inclusion criteria

  • {"criterion_text":"- Participants are eligible to be included in the study if all following criteria apply: A) Participant must be 18 years or older, have documented diagnosis of MDS, have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. For Cohort 1 only: participant must have an endogenous serum erythropoietin (EPO) level of < 500 U/L and no prior ESA treatment. For Cohort 2 only: participant must be refractory or intolerant to prior ESA treatment as defined by any of the following: i) Refractory to prior ESA treatment: Documentation of nonresponse or response that was no longer maintained to prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF). The ESA regimen must have been either: (1) Recombinant human erythropoietin ≥ 40,000 IU/week for at least 8 doses or equivalent; or 1050 mg/kg/week for at least 8 doses or equivalent OR (2) Darbepoetin- darbepoetin alpha ≥ 240 μg every week for at least 12-weeks or equivalent ii) Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF), at any time after introduction due to intolerance or an AE. B) And must require RBC transfusion documented by the following criteria: i) Average transfusion requirement of ≥ 1 units of packed RBCs (pRBCs) confirmed for a minimum of 8-weeks immediately prior to first treatment of luspatercept ii) Hb levels at the time of or within 7 days prior to administration of an RBC transfusion must be ≤ 10.0 g/dL in order for the transfusion to be counted towards meeting eligibility criteria. RBC transfusions administered when Hb levels are > 10 g/dL and/or RBC transfusions administered for elective surgery do not qualify as a required transfusion for the purpose of meeting eligibility criteria"}

Exclusion criteria

  • {"criterion_text":"- A participant will be excluded from the study if they have a secondary MDS, known history of diagnosis of AML, prior allogenic or autologous stem cell transplant, history of allergy or hypersensitivity to study drug components, pregnant, plan to get pregnant or breastfeeding, prior history of malignancies, known significant anemia due to iron, vitamin B12 or folate deficiencies."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Primary endpoint: composite of achievement of RBC-TI for 8-weeks with a concurrent mean Hb increase of ≥ 1 g/dL from Week 1 to Week 24.","definition_or_measurement_approach":"Composite endpoint defined as achievement of red blood cell transfusion independence (RBC-TI) for 8 weeks with an associated concurrent mean hemoglobin (Hb) increase of ≥ 1 g/dL measured from Week 1 to Week 24."}

Secondary endpoints

  • {"endpoint_text":"- Main secondary efficacy endpoints: mean change in total RBC units transfused over a fixed 16 week period from Week 9 to Week 24 and from Week 33 to Week 48. Time from first dose to first onset of RBC TI ≥ 8, 12, and 16 weeks, Maximum duration of RBC-TI for participants who achieve RBC TI ≥ 8- and 16-week period","definition_or_measurement_approach":"Efficacy endpoints include mean change in total RBC units transfused over fixed 16-week intervals (Week 9–24 and Week 33–48); time from first dose to first onset of RBC-TI lasting ≥8, 12, and 16 weeks; and maximum duration of RBC-TI for participants achieving RBC-TI for ≥8 and ≥16 weeks."}
  • {"endpoint_text":"- Main secondary safety endpoint is the type, frequency, severity of AEs, and relationship of adverse events (AEs) to luspatercept from screening to 6 weeks (42-days) post last dose and from Week 1 to Week 48","definition_or_measurement_approach":"Safety endpoints include characterization of adverse events (type, frequency, severity) and assessment of relationship to luspatercept from screening through 6 weeks (42 days) after last dose and over Weeks 1–48."}

Recruitment

Planned Sample Size
72
Recruitment Window Months
38
Consent Approach
Informed consent is obtained from each adult participant (minimum age 18). Country-specific subject information and informed consent forms (ICFs) are provided in local languages and include main ICFs plus optional modules (optional future research, optional sample collection, pregnant-partner ICF). Specific ICF templates are available per Member State (documents listed for ES, CZ, PL, BE, FR, IT, DE).

Methods

  • Investigator Recruitment by Endpoint Clinical Inc. (responsibility listed as Investigator Recruitment in sponsor third-party duties).
  • Country-specific recruitment arrangements documented (recruitment arrangement (K1) documents exist for ES, CZ, PL, BE, FR, IT, DE).
  • Lost-to-follow-up tracing by Omnitrace Corp. (duty: Lost to Follow up Tracing).

Geography

Total Number Of Sites
37
Total Number Of Participants
72

Belgium

Earliest CTIS Part Ii Submission Date
10-01-2024
Latest Decision Or Authorization Date
19-02-2024
Processing Time Days
40
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
UZ Leuven
Department Name
Hematology Dept.
Principal Investigator Name
Mariëlle Beckers
Principal Investigator Email
marielle.beckers@uzleuven.be
Contact Person Name
Mariëlle Beckers
Contact Person Email
marielle.beckers@uzleuven.be
Site Name
Algemeen Ziekenhuis Delta
Department Name
Hematology Dept
Principal Investigator Name
Dries Deeren
Principal Investigator Email
dries.deeren@azdelta.be
Contact Person Name
Dries Deeren
Contact Person Email
dries.deeren@azdelta.be

Czechia

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
13-02-2024
Processing Time Days
28
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Fakultni Nemocnice Brno
Department Name
Interní hematoonkologická klinika
Principal Investigator Name
Jiří Mayer
Principal Investigator Email
mayer.jiri@fnbrno.cz
Contact Person Name
Jiří Mayer
Contact Person Email
mayer.jiri@fnbrno.cz
Site Name
Institute Of Hematology And Blood Transfusion
Department Name
Ústav hematologie a krevni transfuze
Principal Investigator Name
Jaroslav Čermák
Principal Investigator Email
jaroslav.cermak@uhkt.cz
Contact Person Name
Jaroslav Čermák
Contact Person Email
jaroslav.cermak@uhkt.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
I.interní klinika - klinika hematologie
Principal Investigator Name
Anna Jonášová
Principal Investigator Email
anna.jonasova@vfn.cz
Contact Person Name
Anna Jonášová
Contact Person Email
anna.jonasova@vfn.cz

France

Earliest CTIS Part Ii Submission Date
15-01-2024
Latest Decision Or Authorization Date
14-02-2024
Processing Time Days
30
Number Of Sites
7
Number Of Participants
15

Sites

Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Hematology Department
Principal Investigator Name
Sophie Park
Principal Investigator Email
spark@chu-grenoble.fr
Contact Person Name
Sophie Park
Contact Person Email
spark@chu-grenoble.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hematology cell therapy
Principal Investigator Name
Emmanuel Gyan
Principal Investigator Email
Emmanuel.gyan@univ-tours.fr
Contact Person Name
Emmanuel Gyan
Contact Person Email
Emmanuel.gyan@univ-tours.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Hematology Department
Principal Investigator Name
Thomas Cluzeau
Principal Investigator Email
cluzeau.t@chu-nice.fr
Contact Person Name
Thomas Cluzeau
Contact Person Email
cluzeau.t@chu-nice.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hematology Seniors
Principal Investigator Name
Lionel Ades
Principal Investigator Email
Lionel.ades@aphp.fr
Contact Person Name
Lionel Ades
Contact Person Email
Lionel.ades@aphp.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Onco-Hematology and Cell Therapy Department
Principal Investigator Name
Jose Miguel Torregrosa-Diaz
Contact Person Name
Jose Miguel Torregrosa-Diaz
Site Name
Hospices Civils De Lyon
Department Name
Hematology Department
Principal Investigator Name
Maël Heiblig
Principal Investigator Email
Mael.heiblig@chu-lyon.fr
Contact Person Name
Maël Heiblig
Contact Person Email
Mael.heiblig@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Blood diseases service
Principal Investigator Name
Sylvain Thepot
Principal Investigator Email
Sylvain.Thepot@chu-angers.fr
Contact Person Name
Sylvain Thepot
Contact Person Email
Sylvain.Thepot@chu-angers.fr

Italy

Earliest CTIS Part Ii Submission Date
12-01-2024
Latest Decision Or Authorization Date
13-02-2024
Processing Time Days
32
Number Of Sites
8
Number Of Participants
16

Sites

Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
SCDU Ematologia e Terapie cellulari
Principal Investigator Name
Daniela Cilloni
Principal Investigator Email
daniela.cilloni@unito.it
Contact Person Name
Daniela Cilloni
Contact Person Email
daniela.cilloni@unito.it
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
SCDU Ematologia
Principal Investigator Name
Andrea Patriarca
Principal Investigator Email
andrea.patriarca@uniupo.it
Contact Person Name
Andrea Patriarca
Contact Person Email
andrea.patriarca@uniupo.it
Site Name
Humanitas Research Hospital
Department Name
Oncologia ed Ematologia
Principal Investigator Name
Matteo Della Porta
Principal Investigator Email
matteo.della_porta@hunimed.eu
Contact Person Name
Matteo Della Porta
Contact Person Email
matteo.della_porta@hunimed.eu
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
U.O.C. Ematologia e trapianti di midollo
Principal Investigator Name
Fabrizio Pane
Principal Investigator Email
fabpane@unina.it
Contact Person Name
Fabrizio Pane
Contact Person Email
fabpane@unina.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
SC Ematologia I
Principal Investigator Name
Luca Malcovati
Principal Investigator Email
luca.malcovati@unipv.it
Contact Person Name
Luca Malcovati
Contact Person Email
luca.malcovati@unipv.it
Site Name
Careggi University Hospital
Department Name
SOD Ematologia
Principal Investigator Name
Valeria Santini
Principal Investigator Email
dmsc@pec.unifi.it
Contact Person Name
Valeria Santini
Contact Person Email
dmsc@pec.unifi.it
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
Biomedicina e Prevenzione
Principal Investigator Name
Maria Teresa Voso
Principal Investigator Email
voso@med.uniroma2.it
Contact Person Name
Maria Teresa Voso
Contact Person Email
voso@med.uniroma2.it
Site Name
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
Department Name
UOC Ematologia
Principal Investigator Name
Caterina Alati
Principal Investigator Email
caterina.alati@gmail.com
Contact Person Name
Caterina Alati
Contact Person Email
caterina.alati@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
17-01-2024
Latest Decision Or Authorization Date
01-03-2024
Processing Time Days
44
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Hämatologie
Principal Investigator Name
Dominic Brauer
Principal Investigator Email
dominic.brauer@medizin.uni
Contact Person Name
Dominic Brauer
Contact Person Email
dominic.brauer@medizin.uni
Site Name
Studienzentrum am Raschplatz GbR
Principal Investigator Name
Eyck von der Heyde
Principal Investigator Email
vdheyde@onkologie-am-raschplatz.de
Contact Person Name
Eyck von der Heyde
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Klinik und Poliklinik für Innere Medizin III: Hämatologie und Internistische Onkologie
Principal Investigator Name
Katharina Götze
Principal Investigator Email
katharina.goetze@tum.de
Contact Person Name
Katharina Götze
Contact Person Email
katharina.goetze@tum.de

Spain

Earliest CTIS Part Ii Submission Date
22-12-2023
Latest Decision Or Authorization Date
14-02-2024
Processing Time Days
54
Number Of Sites
9
Number Of Participants
18

Sites

Site Name
Complejo Hospitalario Universitario De Ourense
Department Name
Servicio de Hematologia
Principal Investigator Name
Jose Luis Sastre Moral
Principal Investigator Email
joseluis.sastre.moral@sergas.es
Contact Person Name
Jose Luis Sastre Moral
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Haematology department
Principal Investigator Name
Elvira Mora Castera
Principal Investigator Email
mora_elv@gva.es
Contact Person Name
Elvira Mora Castera
Contact Person Email
mora_elv@gva.es
Site Name
Institut Catala D'oncologia
Department Name
Servicio de Hematologia
Principal Investigator Name
Blanca Xicoy Cirici
Principal Investigator Email
bxicoy@iconcologia.net
Contact Person Name
Blanca Xicoy Cirici
Contact Person Email
bxicoy@iconcologia.net
Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Hematologia
Principal Investigator Name
David Valcárcel Ferreira
Principal Investigator Email
dvalcarcel@vhio.net
Contact Person Name
David Valcárcel Ferreira
Contact Person Email
dvalcarcel@vhio.net
Site Name
Institut Catala D'oncologia
Department Name
Servicio de Hematologia
Principal Investigator Name
Montserrat Arnan Sangerman
Principal Investigator Email
marnan@iconcologia.net
Contact Person Name
Montserrat Arnan Sangerman
Contact Person Email
marnan@iconcologia.net
Site Name
Hospital Universitario De Salamanca
Department Name
Servicio de Hematologia
Principal Investigator Name
Maria Diez Campelo
Principal Investigator Email
mdiezcampelo@usal.es
Contact Person Name
Maria Diez Campelo
Contact Person Email
mdiezcampelo@usal.es
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Servicio de Hematologia
Principal Investigator Name
Francisca Hernandez Mohedo
Principal Investigator Email
paquihernandez@yahoo.es
Contact Person Name
Francisca Hernandez Mohedo
Contact Person Email
paquihernandez@yahoo.es
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Servicio de Hematologia
Principal Investigator Name
Maria del Mar Tormo Diaz
Principal Investigator Email
tormo_mar@gva.es
Contact Person Name
Maria del Mar Tormo Diaz
Contact Person Email
tormo_mar@gva.es
Site Name
Hospital Universitario De La Princesa
Department Name
Servicio de Hematologia
Principal Investigator Name
Valle Gomez Garcia de Soria
Principal Investigator Email
vallegomez@yahoo.com
Contact Person Name
Valle Gomez Garcia de Soria
Contact Person Email
vallegomez@yahoo.com

Poland

Earliest CTIS Part Ii Submission Date
10-01-2024
Latest Decision Or Authorization Date
16-02-2024
Processing Time Days
37
Number Of Sites
5
Number Of Participants
7

Sites

Site Name
Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
Department Name
Klinika Hematoonkologii i Transplantacj
Principal Investigator Name
Maria Cioch
Principal Investigator Email
mariacioch@wp.pl
Contact Person Name
Maria Cioch
Contact Person Email
mariacioch@wp.pl
Site Name
Mtz Clinical Research Powered By Pratia
Principal Investigator Name
Krzysztof Mądry
Principal Investigator Email
krzysztof.madry@wum.edu.pl
Contact Person Name
Krzysztof Mądry
Contact Person Email
krzysztof.madry@wum.edu.pl
Site Name
Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
Department Name
Oddział Hematologii
Principal Investigator Name
Aleksandra Butrym
Principal Investigator Email
aleksandra.butrym@gmail.com
Contact Person Name
Aleksandra Butrym
Contact Person Email
aleksandra.butrym@gmail.com
Site Name
Pratia Onkologia Katowice
Principal Investigator Name
Sebastian Grosicki
Principal Investigator Email
sgrosicki@wp.pl
Contact Person Name
Sebastian Grosicki
Contact Person Email
sgrosicki@wp.pl
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Hematologii i Transplantologii - Klinika Hematologii
Principal Investigator Name
Agnieszka Wierzbowska
Principal Investigator Email
agawierzbowska@wp.pl
Contact Person Name
Agnieszka Wierzbowska
Contact Person Email
agawierzbowska@wp.pl

Sponsor

Primary sponsor

Full Name
Celgene Corp.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Pharmaceutical Product Development LLC
Responsibilities
Monitoring, SUSAR Reporting, Feasibility, Vendor Management, Clinical, Management & Monitoring, Site Start up, Services, Site Monitoring & Site, Management, Pharmacovigilance, Data Analytics
Name
Q2 Solutions, 2 Squared Solutions LLC
Responsibilities
Routine clinical pathology testing, Clinical Chemistry, Clinical haematology, Clinical microbiology, Central Lab Services, IHC Biomarker, expression analysis (PD-L1), other APH
Name
Endpoint Clinical Inc.
Responsibilities
Investigator Recruitment, IVRS - tratment randomization, Subject Number Assignment, Treatment/Arm Assignment, Drug (re) Supplies Assignment
Name
QPS LLC
Responsibilities
bioanalytical analysis, Nab

Third parties

  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Provide licensing services for use of the Quality of Life Questionnaire-Core 30 and translations","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Q2 Solutions, 2 Squared Solutions LLC","duties_or_roles":"Routine clinical pathology testing, Clinical Chemistry, Clinical haematology, Clinical microbilogy, Central Lab Services, IHC Biomarker, expression analysis (PD-L1), other APH","organisation_type":"Industry"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Monitoring, SUSAR Reporting, Feasibility, Vendor Management, Clinical, Management & Monitoring, Site Start up, Services, Site Monitoring & Site, Management, Pharmacovigilance, Data Analytics","organisation_type":"Pharmaceutical company"}
  • {"country":"India","full_name":"Accenture Solutions Private Limited","duties_or_roles":"Pharmacovigilance: Medical review & Cases, Data Entry.; Pharmacovigilance: Medical review & Cases, Data Entry.; Embarc operations; (also listed with code 6 duties)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"Investigator Recruitment, IVRS - tratment randomization, Subject Number Assignment, Treatment/Arm Assignment, Drug (re) Supplies Assignment","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"MLL Dx GmbH","duties_or_roles":"Biomarkers - genetics/genomics, FISH analyses","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Lost to Follow up Tracing","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"QPS LLC","duties_or_roles":"bioanalytical analysis, Nab","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Reblozyl 75 mg powder for solution for injection
Active Substance
LUSPATERCEPT
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Authorised (marketing authorisation EU/1/20/1452/002)
Orphan Designation
Yes
Starting Dose
1.75 mg/kg
Dose Levels
1.75 mg/kg (highest starting dose stated)
Maximum Dose
60.8 mg/kg (max total amount as listed)
Investigational Product Name
Reblozyl 25 mg powder for solution for injection
Active Substance
LUSPATERCEPT
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Authorised (marketing authorisation EU/1/20/1452/001)
Orphan Designation
Yes
Starting Dose
1.75 mg/kg
Dose Levels
1.75 mg/kg (highest starting dose stated)
Maximum Dose
60.8 mg/kg (max total amount as listed)

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