Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03481738 |
| Other study ID # |
AG348-C-008 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 23, 2018 |
| Est. completion date |
May 31, 2027 |
Study information
| Verified date |
May 2024 |
| Source |
Agios Pharmaceuticals, Inc. |
| Contact |
Medical Information |
| Phone |
833-228-8474 |
| Email |
MedInfo[@]agios.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial 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.
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.
