Purpose

This study is an observational (ie, non-interventional), longitudinal, multicenter, global registry for patients with pyruvate kinase (PK) deficiency, a rare non-spherocytic 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 assessments are strongly encouraged to enhance longitudinal understanding of PK deficiency; however, no specific assessments are set or required by this Registry protocol.

Condition

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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 PKLR gene mutations (either compound heterozygote or homozygous recessive).
  • The participant or the parent/guardian of the participant must be willing and able to give written informed consent and/or assent

Exclusion Criteria

  • Participants who are actively enrolled in an Agios-sponsored clinical study involving treatment with a PK activator are not eligible to enroll in the Registry until after they have completed or withdrawn from that clinical study

Study Design

Phase
Study Type
Observational [Patient Registry]
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
PKD Diagnosed Patients diagnoses with PK Deficiency by PKLR genetic mutation analysis (either compound heterozygote or homozygous recessive) as well as clinical features

Recruiting Locations

Phoenix Childrens Hospital
Phoenix, Arizona 85016

Arkansas Children's Hospital
Little Rock, Arkansas 72202

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

Children's Hospital of Orange County
Orange, California 92868

Boston Children's Hospital
Boston, Massachusetts 02115

UMass Memorial Medical Center
Worcester, Massachusetts 01655-0002

Children's Hospital of Michigan
Detroit, Michigan 48201

Duke University Medical Center
Durham, North Carolina 27710

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104

St Jude Children's Research Hospital
Memphis, Tennessee 38105

Primary Children's Hospital
Salt Lake City, Utah 84113

University of Vermont Medical Center
Burlington, Vermont 05401

More Details

NCT ID
NCT03481738
Status
Recruiting
Sponsor
Agios Pharmaceuticals, Inc.

Study Contact

Medical Information
833-228-8474
MedInfo@agios.com

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 PKLR gene mutations (either compound heterozygote or homozygous recessive).

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).

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 insure 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.