Clinical trial • Phase II/III • Haematology

MITAPIVAT for Sickle cell disease | Anemia

Phase II/III trial of MITAPIVAT for Sickle cell disease | Anemia.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Sickle cell disease | Anemia
Trial Stage
Phase II/III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
15-07-2024
First CTIS Authorization Date
13-08-2024

Trial design

Randomised, open-label, placebo to match mitapivat tablets (matched placebo). active comparator arms: mitapivat 50 mg orally bid (dose level 1) and mitapivat 100 mg orally bid (dose level 2); placebo arm matched; dosing schedule: bid oral administration.-controlled, adaptive Phase II/III trial in Belgium, Netherlands, Germany and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo to match Mitapivat tablets (matched placebo). Active comparator arms: Mitapivat 50 mg orally BID (Dose Level 1) and Mitapivat 100 mg orally BID (Dose Level 2); placebo arm matched; dosing schedule: BID oral administration.
Adaptive
True, operationally seamless Phase 2/3 design: decision to proceed to Phase 3 and selection of dose for Phase 3 are based on results of the Phase 2 primary endpoint analysis and additional considerations (no detailed dose-escalation stopping rules provided in the public summary).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
210
Trial Duration For Participant
1904

Eligibility

Recruits 210 paediatric patients.

Pregnancy Exclusion
Pregnant or breastfeeding.
Vulnerable Population
Adolescents are included (age 16–17 allowed if Tanner Stage 5 documented). The protocol requires written informed assent/consent; for subjects under 18 (or younger than local legal adulthood) parental permission and child assent will be obtained. Adolescent assent and age-specific ICF documents are provided (adolescent assent forms and main ICFs in multiple languages are included among submitted documents).

Inclusion criteria

  • {"criterion_text":"- Age ≥16 years; subjects age 16 or 17 years must be documented Tanner Stage 5 (see Appendix 3).\n- Documented diagnosis of sickle cell disease (SCD) (HbSS, HbSC [combined heterozygosity for hemoglobins S and C], HbS/β0-thalassemia, HbS/β+-thalassemia, or other sickle cell syndrome variants).\n- At least 2 sickle cell pain crises (SCPCs) (defined in Section 8.5.2.1) and no more than 10 SCPCs in the 12 months prior to providing informed assent/consent.\n- Hemoglobin ≥5.5 and ≤10.5 g/dL. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.\n- If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days prior to randomization. Discontinuation of hydroxyurea requires a 90-day washout prior to informed assent/consent.\n- Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, one of which must be considered highly effective, from the time of providing informed assent/consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method (see Appendix 2).\n- Written informed assent/consent (for subjects under 18 years of age, or prior to the age at which a subject is considered legally an adult per local regulations, parental permission and child assent will be obtained) must be obtained before any study-related procedures are conducted and subjects must be willing to comply with all study procedures for the duration of the study."}

Exclusion criteria

  • {"criterion_text":"- Pregnant or breastfeeding.\n- Other protocol defined exclusion criteria may apply.\n- Receiving regularly scheduled transfusions.\n- Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days prior to providing informed assent/consent or during the Screening Period. A hospitalization is defined as an in-patient admission to a hospital that may or may not be preceded by an emergency room or out patient clinic visit. A visit to an emergency room that does not result in an in-patient admission does not meet the definition of hospitalization\n- Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of voxelotor, crizanlizumab, and L-glutamine must have been administered at least 90 days before starting study drug.\n- Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug.\n- Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial.\n- Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).\n- Any medical, hematological, psychological, or behavioral condition(s), including alcohol use disorder, or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study.\n- Receiving herbal or dietary supplements that have not been stable in dose and preparation for ≥8 weeks prior to randomization."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 compared with baseline\n- Annualized rate of SCPCs (as defined in Section 8.5.2.1)","definition_or_measurement_approach":"Hemoglobin (Hb) response: ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 versus baseline. Annualized rate of SCPCs: rate calculated per protocol definition (see Section 8.5.2.1) as annualized count of sickle cell pain crises."}

Secondary endpoints

  • {"endpoint_text":"- Average change from baseline in Hb concentration from Week 24 through Week 52\n- Average change from baseline in indirect bilirubin from Week 24 through Week 52\n- Average change from baseline in percent reticulocyte from Week 24 through Week 52\n- Average change from baseline in Patient-Reported Outcomes Measurement Information System®(PROMIS) Fatigue 13a Short Form (SF) scores from Week 24 through Week 52\n- Annualized frequency of hospitalizations for SCPC","definition_or_measurement_approach":"All listed secondary endpoints are measured as average change from baseline over the interval Week 24 through Week 52 (for lab and PRO endpoints). Annualized frequency of hospitalizations for SCPC is calculated as the number of hospitalizations for SCPC normalized to a 1-year period."}

Recruitment

Planned Sample Size
210
Recruitment Window Months
100
Consent Approach
Written informed consent is required. For subjects under 18 years of age (or under the local age of legal adulthood) parental permission and child assent are required; adolescent assent forms and age-appropriate ICFs are provided. Main ICFs and adolescent assent documents exist in multiple languages (English, Dutch, French, German, Italian as provided in submitted documents). Specific pregnant participant ICF and pregnant partner ICF are provided where applicable.

Geography

Total Number Of Sites
20
Total Number Of Participants
66

Belgium

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
531
Number Of Sites
6
Number Of Participants
6

Sites

Site Name
Hopital Erasme
Department Name
Haematology
Principal Investigator Name
Martin Colard
Principal Investigator Email
martin.colard@hubruxelles.be
Contact Person Name
Martin Colard
Contact Person Email
martin.colard@hubruxelles.be
Site Name
Het Ziekenhuisnetwerk Antwerpen
Department Name
Haematology
Principal Investigator Name
Tom Eyckmans
Principal Investigator Email
tom.eyckmans@zna.be
Contact Person Name
Tom Eyckmans
Contact Person Email
tom.eyckmans@zna.be
Site Name
CHC MontLegia
Department Name
Pediatric Haemato-oncology
Principal Investigator Name
Christophe Chantrain
Principal Investigator Email
christophe.chantrain@chc.be
Contact Person Name
Christophe Chantrain
Contact Person Email
christophe.chantrain@chc.be
Site Name
Het Ziekenhuisnetwerk Antwerpen
Department Name
Haematology
Principal Investigator Name
Tom Eyckmans
Principal Investigator Email
tom.eyckmans@zna.be
Contact Person Name
Tom Eyckmans
Contact Person Email
tom.eyckmans@zna.be
Site Name
Centre Hospitalier Regional De La Citadelle
Department Name
Haematology
Principal Investigator Name
Kaoutar Hafraoui
Principal Investigator Email
khafraoui@chuliege.be
Contact Person Name
Kaoutar Hafraoui
Contact Person Email
khafraoui@chuliege.be
Site Name
Antwerp University Hospital
Department Name
Haematology
Principal Investigator Name
Ann Van de Velde
Principal Investigator Email
ann.van.de.velde@uza.be
Contact Person Name
Ann Van de Velde
Contact Person Email
ann.van.de.velde@uza.be

Netherlands

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
531
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Hematology
Principal Investigator Name
Anita Rijneveld
Principal Investigator Email
A.Rijneveld@erasmusmc.nl
Contact Person Name
Anita Rijneveld
Contact Person Email
A.Rijneveld@erasmusmc.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Van Creveldkliniek
Principal Investigator Name
Eduard van Beers
Principal Investigator Email
e.j.vanbeers-3@umcutrecht.nl
Contact Person Name
Eduard van Beers
Contact Person Email
e.j.vanbeers-3@umcutrecht.nl

Germany

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
20-01-2026
Processing Time Days
532
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Principal Investigator Name
Ferras Alashkar
Principal Investigator Email
ferras.alashkar@uk-essen.de
Contact Person Name
Ferras Alashkar
Contact Person Email
ferras.alashkar@uk-essen.de

Italy

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
21-01-2026
Processing Time Days
533
Number Of Sites
5
Number Of Participants
12

Sites

Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro
Principal Investigator Name
Manuela Balocco
Principal Investigator Email
manuela.balocco@galliera.it
Contact Person Name
Manuela Balocco
Contact Person Email
manuela.balocco@galliera.it
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
U.O.C. Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici
Principal Investigator Name
Rosario Di Maggio
Principal Investigator Email
rdm83@hotmail.it
Contact Person Name
Rosario Di Maggio
Contact Person Email
rdm83@hotmail.it
Site Name
Universita' Degli Studi Di Modena E Reggio Emilia
Department Name
S.C. Medicina Interna
Principal Investigator Name
Francesca Ferrara
Principal Investigator Email
ferrara.francesca@aou.mo.it
Contact Person Name
Francesca Ferrara
Contact Person Email
ferrara.francesca@aou.mo.it
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
U.O.S.D. Malattie Rare del Globulo Rosso Dipartimento Onco-ematologico e pneumoematologico
Principal Investigator Name
Paolo Ricchi
Principal Investigator Email
paolo.ricchi@aocardarelli.it
Contact Person Name
Paolo Ricchi
Contact Person Email
paolo.ricchi@aocardarelli.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
U.O.C. Clinica Pediatrica
Principal Investigator Name
Silverio Perrotta
Principal Investigator Email
Silverio.PERROTTA@unicampania.it
Contact Person Name
Silverio Perrotta

France

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
538
Number Of Sites
6
Number Of Participants
22

Sites

Site Name
Oncopole Claudius Regaud
Department Name
Service de Médecine Interne
Principal Investigator Name
Pierre COUGOUL
Principal Investigator Email
cougoul.pierre@iuct-oncopole.fr
Contact Person Name
Pierre COUGOUL
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Département de Médecine Interne
Principal Investigator Name
Estelle JEAN-MIGNARD
Principal Investigator Email
estelle.jean@ap-hm.fr
Contact Person Name
Estelle JEAN-MIGNARD
Contact Person Email
estelle.jean@ap-hm.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service de Neurologie
Principal Investigator Name
Arnaud DESCLAUX
Principal Investigator Email
arnaud.desclaux@chu-bordeaux.fr
Contact Person Name
Arnaud DESCLAUX
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Unité des Maladies génétiques du globule rouge
Principal Investigator Name
Pablo BARTOLUCCI
Principal Investigator Email
pablo.bartolucci@aphp.fr
Contact Person Name
Pablo BARTOLUCCI
Contact Person Email
pablo.bartolucci@aphp.fr
Site Name
CHU Guadeloupe
Department Name
Service de Médecine Interne
Principal Investigator Name
Emmanuelle BERNIT
Principal Investigator Email
emmanuelle.bernit@chu-guadeloupe.fr
Contact Person Name
Emmanuelle BERNIT
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service de Médecine Interne
Principal Investigator Name
Jean-Benoit ARLET
Principal Investigator Email
jean-benoit.arlet@aphp.fr
Contact Person Name
Jean-Benoit ARLET
Contact Person Email
jean-benoit.arlet@aphp.fr

Sponsor

Primary sponsor

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

Contract research organisations

Name
PPD Development LP
Responsibilities
Multiple study support functions (codes listed in sponsor duties); laboratory and operational support (as listed among sponsorDuties).
Name
PPD International Holdings LLC
Responsibilities
Laboratory/operational support (sponsor duties listed).
Name
QPS LLC
Responsibilities
PK, PD Analysis
Name
Fortrea Inc.
Responsibilities
Clinical development support
Name
Endpoint Clinical Inc.
Responsibilities
IVRS Phase 2
Name
Medidata Solutions Inc.
Responsibilities
Data platform/solutions
Name
Suvoda LLC
Responsibilities
Clinical trial conduct/support
Name
Bioclinica Inc.
Responsibilities
Laboratory/clinical data support
Name
Almac Clinical Services Limited
Responsibilities
Clinical supply/packaging (code 14 listed among sponsor duties)

Third parties

  • {"country":"United States","full_name":"Colorado Prevention Center","duties_or_roles":"6 min walking test site training and central read of endpoint","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS Phase 2","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"QPS LLC","duties_or_roles":"PK, PD Analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Intrinsic Lifesciences LLC","duties_or_roles":"analysis of exploratory disease markers","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"travel arrangements & patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
MITAPIVAT
Active Substance
MITAPIVAT
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Marketing information present (miaNumber: UK MIA(IMP) 20377); prodAuthStatus=1
Starting Dose
50 mg and 100 mg (both used as Dose Level 1 and Dose Level 2 in randomization)
Dose Levels
50 mg; 100 mg
Frequency
BID
Maximum Dose
200 mg/day
Dose Escalation Increase
Initial doses: 50 mg and 100 mg; no escalation scheme specified in public summary
Investigational Product Name
Placebo to Match Mitapivat (tablets/granules as described)
Modality
Other

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