Pyruvate Kinase Deficiency Global Longitudinal Registry

NCT ID: NCT03481738

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-04-23

Study Completion Date

2027-05-31

Brief Summary

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This study is an observational (ie, noninterventional), longitudinal, multicenter, global registry for patients with pyruvate kinase (PK) deficiency, a rare nonspherocytic hemolytic anemia.

This Registry will be open for enrollment for 7 years and all enrolled participants will be followed prospectively for a minimum of 2 years, and up to 9 years.

Data will be collected from participating Registry Physicians, participants, and, where appropriate, parents/guardians who have provided informed consent or assent (where relevant) and authorization pursuant to applicable laws and regulations.

Data should include demographic, clinical, and treatment data; and other data of relevance to the management of patients with PK deficiency. Annual chart review and data entry are expected in order to enhance longitudinal understanding of PK deficiency; however, no specific protocol schedule of assessment is required by this Registry protocol.

Detailed Description

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Data will be submitted to the Registry via electronic case report forms (eCRFs). Relevant datasets, such as historical trial data, claims, medical records, or central lab data will be electronically integrated into the Registry or Registry reporting data sets.

Participants of all ages with a confirmed diagnosis of PK deficiency via genetic testing will be eligible to participate in this Registry. Diagnosis may be made on the basis of clinical features consistent with PK deficiency together with the presence of 2 or more PKLR gene mutations.

For novel or indeterminate PKLR gene mutations, participants will be deemed eligible if, in the opinion of the investigator, the reported PKLR gene mutations are sufficient to support a diagnosis of PK deficiency. Pyruvate kinase deficiency-relevant data will be entered by Registry Physicians or their designee for any and all participant visits. Disease parameters (eg, hemoglobin, reticulocyte counts), treatment and management options (splenectomy, transfusions, iron chelation, bone marrow transplant or pharmacological therapies) and resource utilization (eg, hospitalizations) will be evaluated to describe the natural history, treatments and outcomes, variability in clinical care and disease burden in patients with PK deficiency.

As a longitudinal observational study, the PK deficiency Registry may also serve as a data collection platform to address specific research objectives that may emerge over the duration of the study.

All data collection efforts will abide by this protocol and be prospectively disclosed in the Registry informed consent. If new assessments become of interest, they may be addressed via specific substudies (eg, patient-reported outcomes, biobanking), each requiring their own specific protocol and consent approved by Institutional Review Broad/Independent Ethics Committee (IRB/IEC). These studies may utilize a decentralized operational model with remote data capture. An IRB/IEC approved PEAK participant invitation process and participant self-opt-in registration may be utilized where country regulations and site policies allow.

This Registry, with the appropriate participant (and or parent/guardian) consent/assent, may incorporate retrospective data from other properly consented studies done for the purpose of examining the longitudinal natural history of PK deficiency. As necessary, data integration plan(s) will be developed to allow efficient and fit-for-purpose integration of data from other studies or data sets into this Registry.

Separate detailed statistical analysis plans (SAPs), addressing specific objectives, will be developed before the analyses during and at the end of the study. Due to the nature of the observational study, most statistical analyses will focus on descriptive statistics, including estimates and confidence intervals (CI) as appropriate. Additional statistical modeling of the data may be conducted. However, any p-values reported for hypothesis testing will be considered exploratory and therefore hypothesis-generating by nature. All data will be analyzed as collected in the database. Missing data, in general, will not be imputed; the modeling, eg, repeated measures mixed-effect models (MMRM) or generalized linear mixed effect model (GLIMMIX) will make use of all available data in the analyses. Any additional imputation techniques, if deemed necessary, will be discussed in the statistical analysis plan(s).

To ensure compliance with Good Clinical Practice and all applicable regulatory requirements, the Sponsor and its representatives will conduct and manage several plans that will ensure quality control. These will include:

* A documented sourcing procedure for all representatives and technology managing, collecting, or reporting on Registry data
* Assurance of FDA 21 CFR Part 11, EU-US Privacy Shield, and equivalent regulations regarding data security, controls, and audit trail of study data
* Assurance of the European Union regulation 2016/679 describing the appropriate use of personal data in scientific research
* Practices and methods for the protection of all participant privacy in relation to study data collection
* A training plan for site initiation and documentation
* Data entry guidelines that will assist all study sites with the completion of eCRFs
* A data monitoring and management plan that will outline the processes and procedures for reviewing, querying, and resolving data quality issues with study sites
* A site monitoring plan for the Sponsor and its representatives that will outline the frequency, requirements, and nature of the site monitoring visits for purposes of insuring data quality.

The Registry will be overseen by a Scientific Steering Committee, comprised of international experts involved in the research, diagnosis, and/or care of patients with PK deficiency. The Scientific Steering Committee's activities may include further defining the objectives and scientific direction of the Registry, advising on additional clinical data to be captured, and facilitating analysis and dissemination of Registry data via medical conferences and peer-reviewed publications.

Conditions

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Pyruvate Kinase Deficiency

Keywords

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Glycolytic enzymopathy Congenital Nonspherocytic hemolytic anemia (CNSA) PKD

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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PKD Diagnosed

Participants diagnosed with PK deficiency by the presence of 2 or more PKLR gene mutations as well as clinical features.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Participants of all ages with a confirmed diagnosis of PK deficiency via genetic testing are eligible to enroll;
* Participants will be considered for enrollment on the basis of clinical features consistent with PK deficiency together with the presence of 2 or more PKLR gene mutations. For novel or indeterminate PKLR gene mutations, participants will be deemed eligible if, in the opinion of the investigator, the reported PKLR gene mutations are sufficient to support a diagnosis of PK deficiency;
* The participant or the parent/guardian of the participant must be willing and able to give written informed consent and/or assent. E-consent or remote consent may be utilized where permissible as applicable if country regulations and site policies allow.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva Gallagher, VP, Medical Affairs

Role: STUDY_CHAIR

Agios Pharmaceuticals, Inc.

Locations

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Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Saint Josephs Healthcare System

Hamilton, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

St. Justine Hospital

Montreal, Quebec, Canada

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Ustav hematologie a krevni transfuze

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Copenhagen University Hospital

Herlev, , Denmark

Site Status

Hopital Necker

Paris, , France

Site Status

Charite - Universitatsmedizin Berlin

Berlin, , Germany

Site Status

Evangelisches Krankenhaus Bielefeld gGmbH

Bielefeld, , Germany

Site Status

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Kinder- und Jugendarztpraxis

Munich, , Germany

Site Status

Universitatsklinikum Wurzburg

Würzburg, , Germany

Site Status

St James's Hospital

Dublin, , Ireland

Site Status

Presidio Ospedaliero di Pescara

Pescara, Abruzzo, Italy

Site Status

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Napoli, Campania, Italy

Site Status

E O Ospedali Galliera

Genoa, Liguria, Italy

Site Status

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Ospedale S Eugenio

Roma, , Italy

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

Centro Hospitalar E Universitario de Coimbra EPE

Coimbra, , Portugal

Site Status

Centro Hospitalar Lisboa Central- Hospital Dona Estefania

Lisbon, , Portugal

Site Status

Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E

Porto, , Portugal

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona, Spain

Site Status

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Site Status

Hospital de La Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital de Tortosa Verge de la Cinta

Tortosa, , Spain

Site Status

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Site Status

Siriraj Hospital Mahidol University

Bangkok, , Thailand

Site Status

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Hammersmith Hospital

London, London, City of, United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Canada Czechia Denmark France Germany Ireland Italy Netherlands Portugal South Korea Spain Switzerland Thailand Turkey (Türkiye) United Kingdom

References

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Grace RF, van Beers EJ, Vives Corrons JL, Glader B, Glenthoj A, Kanno H, Kuo KHM, Lander C, Layton DM, Pospisilova D, Viprakasit V, Li J, Yan Y, Boscoe AN, Bowden C, Bianchi P. The Pyruvate Kinase Deficiency Global Longitudinal (Peak) Registry: rationale and study design. BMJ Open. 2023 Mar 23;13(3):e063605. doi: 10.1136/bmjopen-2022-063605.

Reference Type DERIVED
PMID: 36958777 (View on PubMed)

Related Links

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https://PEAKRegistry.com

Overview of the PEAK Registry

Other Identifiers

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AG348-C-008

Identifier Type: -

Identifier Source: org_study_id