Pyruvate Kinase Deficiency Global Longitudinal Registry (PEAK Registry)

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.

Study Overview

• Status: Recruiting
• Conditions: Pyruvate Kinase Deficiency

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 833-228-8474; Email: MedInfo@agios.com

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • Saint Josephs Healthcare System
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Recruiting
      • St. Justine Hospital
• Czechia
  • Olomouc, Czechia, 779 00
    • Recruiting
    • Fakultní nemocnice Olomouc
  • Praha 2, Czechia, 128 20
    • Recruiting
    • Ustav hematologie a krevni transfuze
  • Praha 5, Czechia, 150 06
    • Recruiting
    • Fakultní nemocnice v Motole
• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Copenhagen University Hospital
• France
  • Paris, France, 75743
    • Recruiting
    • Hopital Necker
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité - Universitätsmedizin Berlin
  • Bielefeld, Germany, 33617
    • Recruiting
    • Evangelisches Krankenhaus Bielefeld gGmbH
  • Heidelberg, Germany, 69120
    • Terminated
    • Universitätsklinikum Heidelberg
  • Munich, Germany, 81377
    • Recruiting
    • Kinder- und Jugendarztpraxis
  • Wuerzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg
• Ireland
  • Dublin, Ireland, D08 NHY1
    • Recruiting
    • St James's Hospital
• Italy
  • Milano, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80131
    • Withdrawn
    • AORN A Cardarelli
  • Padova, Italy, 35128
    • Withdrawn
    • Azienda Ospedaliera di Padova
  • Roma, Italy, 144
    • Recruiting
    • Ospedale S Eugenio
  • Abruzzo
    • Pescara, Abruzzo, Italy, 65125
      • Recruiting
      • Presidio Ospedaliero di Pescara
  • Campania
    • Napoli, Campania, Italy
      • Recruiting
      • AOU dell'Università degli Studi della Campania Luigi Vanvitelli
  • Liguria
    • Genova, Liguria, Italy, 16128
      • Recruiting
      • E O Ospedali Galliera
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Netherlands
  • Utrecht, Netherlands, 3508 GA
    • Recruiting
    • Universitair Medisch Centrum Utrecht
• Portugal
  • Coimbra, Portugal, 3041-853
    • Recruiting
    • Centro Hospitalar E Universitário de Coimbra EPE
  • Lisboa, Portugal, 1169-045
    • Recruiting
    • Centro Hospitalar Lisboa Central- Hospital Dona Estefania
  • Porto, Portugal, 4200-072
    • Recruiting
    • Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E
• Spain
  • Barcelona, Spain, 8041
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Nino Jesus
  • Tortosa, Spain, 43500
    • Recruiting
    • Hospital de Tortosa Verge de la Cinta
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Hospital Universitario Germans Trias i Pujol
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Deu - PIN
• Switzerland
  • Lausanne, Switzerland, CH 1011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois
• Thailand
  • Bangkok, Thailand
    • Recruiting
    • Siriraj Hospital Mahidol University
• Turkey
  • Ankara, Turkey
    • Recruiting
    • Hacettepe University Medical Faculty
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Recruiting
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • London, City Of
    • London, London, City Of, United Kingdom, W12 0HS
      • Recruiting
      • Hammersmith Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Childrens Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Children's Healthcare of Atlanta
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01655-0002
      • Recruiting
      • Umass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Children's Hospital of Michigan
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St Jude Children's Research Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • Primary Children's Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Recruiting
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited or referred by physicians who treat hemolytic anemias at approximately 60 sites in approximately 20 countries.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
PKD Diagnosed; Participants diagnosed with PK deficiency by the presence of 2 or more PKLR gene mutations as well as clinical features.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Course of PK Deficiency	To develop an understanding of the longitudinal clinical implications of PK deficiency, including disease natural history, treatments and outcomes, and variability in clinical care and disease burden.	9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Disease	To understand the prevalence, incidence, and severity of complications associated with PK deficiency.	9 years
Disease Impact on Pregnancy	To evaluate pregnancy outcomes.	9 years
Clinical Management Assistance	To provide a source of longitudinal data to assist physicians with clinical management of individual patients.	9 years
Global Repository	To act as a global repository for potential data from other properly consented PK deficiency-related studies to support aggregate and comparative analyses.	9 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic	To examine a possible correlation between PKLR genotype and PK deficiency clinical phenotype.	9 years

Collaborators and Investigators

• Sponsor: Agios Pharmaceuticals, Inc.
• Investigators: Study Chair: Eva Gallagher, VP, Medical Affairs, Agios Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Overview of the PEAK Registry

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: March 22, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PKD; Glycolytic enzymopathy; Congenital Nonspherocytic hemolytic anemia (CNSA)
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia, Hemolytic, Congenital Nonspherocytic; Pyruvate Metabolism, Inborn Errors
• Other Study ID Numbers: AG348-C-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No