Clinical trial NCT03481738: Pyruvate Kinase Deficiency Global Longitudinal Registry
Official title: Pyruvate Kinase Deficiency Global Longitudinal Registry
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pyruvate Kinase Deficiency
Keywords: Glycolytic enzymopathy
Congenital Nonspherocytic hemolytic anemia (CNSA)
PKD
Lead sponsor: Agios Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Course of PK Deficiency
timeFrame: 9 years
Secondary outcomes:
measure: Severity of Disease
timeFrame: 9 years
measure: Disease Impact on Pregnancy
timeFrame: 9 years
measure: Clinical Management Assistance
timeFrame: 9 years
measure: Global Repository
timeFrame: 9 years
Other outcomes:
measure: Genetic
timeFrame: 9 years
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Hamilton
country: Canada
facility: Saint Josephs Healthcare System
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: St. Justine Hospital
state: Quebec
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 2
country: Czechia
facility: Ustav hematologie a krevni transfuze
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Herlev
country: Denmark
facility: Copenhagen University Hospital
city: Paris
country: France
facility: Hopital Necker
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld gGmbH
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Munich
country: Germany
facility: Kinder- und Jugendarztpraxis
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Dublin
country: Ireland
facility: St James's Hospital
city: Pescara
country: Italy
facility: Presidio Ospedaliero di Pescara
state: Abruzzo
city: Napoli
country: Italy
facility: AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
state: Campania
city: Genova
country: Italy
facility: E O Ospedali Galliera
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Ospedale S Eugenio
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitario de Coimbra EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Central- Hospital Dona Estefania
city: Porto
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu - PIN
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Tortosa
country: Spain
facility: Hospital de Tortosa Verge de la Cinta
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: London, City Of
city: London
country: United Kingdom
facility: Kings College Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Agios Pharmaceuticals, Inc.
name: Eva Gallagher, VP, Medical Affairs
role: STUDY_CHAIR
References: