Pyruvate Kinase Deficiency Global Longitudinal Registry
- Conditions
- Pyruvate Kinase Deficiency
- Registration Number
- NCT03481738
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 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.
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Clinical Course of PK Deficiency 9 years 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.
- Secondary Outcome Measures
Name Time Method Severity of Disease 9 years To understand the prevalence, incidence, and severity of complications associated with PK deficiency.
Disease Impact on Pregnancy 9 years To evaluate pregnancy outcomes.
Global Repository 9 years To act as a global repository for potential data from other properly consented PK deficiency-related studies to support aggregate and comparative analyses.
Clinical Management Assistance 9 years To provide a source of longitudinal data to assist physicians with clinical management of individual patients.
Trial Locations
- Locations (54)
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Saint Josephs Healthcare System
🇨🇦Hamilton, Ontario, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
St. Justine Hospital
🇨🇦Montreal, Quebec, Canada
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Ustav hematologie a krevni transfuze
🇨🇿Praha 2, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Copenhagen University Hospital
🇩🇰Herlev, Denmark
Hopital Necker
🇫🇷Paris, France
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Evangelisches Krankenhaus Bielefeld gGmbH
🇩🇪Bielefeld, Germany
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Kinder- und Jugendarztpraxis
🇩🇪Munich, Germany
Universitatsklinikum Wurzburg
🇩🇪Wuerzburg, Germany
St James's Hospital
🇮🇪Dublin, Ireland
Presidio Ospedaliero di Pescara
🇮🇹Pescara, Abruzzo, Italy
AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Campania, Italy
E O Ospedali Galliera
🇮🇹Genova, Liguria, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
AORN A Cardarelli
🇮🇹Napoli, Italy
Azienda Ospedaliera Di Padova
🇮🇹Padova, Italy
Ospedale S Eugenio
🇮🇹Roma, Italy
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Centro Hospitalar E Universitario de Coimbra EPE
🇵🇹Coimbra, Portugal
Centro Hospitalar Lisboa Central- Hospital Dona Estefania
🇵🇹Lisboa, Portugal
Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E
🇵🇹Porto, Portugal
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Sant Joan de Deu - PIN
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Hospital de La Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital de Tortosa Verge de la Cinta
🇪🇸Tortosa, Spain
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Siriraj Hospital Mahidol University
🇹ðŸ‡Bangkok, Thailand
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Hammersmith Hospital
🇬🇧London, London, City Of, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle upon Tyne, United Kingdom