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Pyruvate Kinase Deficiency Global Longitudinal Registry (PEAK Registry)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03481738
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : March 9, 2020
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Tracking Information
First Submitted Date March 22, 2018
First Posted Date March 29, 2018
Last Update Posted Date March 9, 2020
Actual Study Start Date April 23, 2018
Estimated Primary Completion Date May 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 22, 2018)
Clinical Course of PK Deficiency [ Time Frame: 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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 22, 2018)
  • Severity of Disease [ Time Frame: 9 years ]
    To understand the prevalence, incidence, and severity of complications associated with PK deficiency
  • Disease Impact on Pregnancy [ Time Frame: 9 years ]
    To evaluate pregnancy outcomes
  • Clinical Management Assistance [ Time Frame: 9 years ]
    To provide a source of longitudinal data to assist physicians with clinical management of individual patients
  • Global Repository [ Time Frame: 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 22, 2018)
Genetic [ Time Frame: 9 years ]
To examine a possible correlation between PKLR genotype and PK deficiency clinical phenotype
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title Pyruvate Kinase Deficiency Global Longitudinal Registry
Official Title Pyruvate Kinase Deficiency Global Longitudinal Registry
Brief Summary

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.

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.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 2 Years
Biospecimen Not Provided
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.
Condition Pyruvate Kinase Deficiency
Intervention Not Provided
Study Groups/Cohorts PKD Diagnosed
Patients diagnoses with PK Deficiency by PKLR genetic mutation analysis (either compound heterozygote or homozygous recessive) as well as clinical features
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 22, 2018)
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 2027
Estimated Primary Completion Date May 2027   (Final data collection date for primary outcome measure)
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 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
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contact: Medical Information 833-228-8474
Listed Location Countries Canada,   Czechia,   Denmark,   France,   Germany,   Italy,   Netherlands,   Portugal,   Spain,   Thailand,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number NCT03481738
Other Study ID Numbers AG348-C-008
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Agios Pharmaceuticals, Inc.
Study Sponsor Agios Pharmaceuticals, Inc.
Collaborators Not Provided
Study Chair: Eva Gallagher, VP, Medical Affairs Agios Pharmaceuticals, Inc.
PRS Account Agios Pharmaceuticals, Inc.
Verification Date March 2020