Pyruvate Kinase Deficiency Natural History Study

Pyruvate Kinase Deficiency Clinical Trial

— PKD NHS  

Official title:

Pyruvate Kinase Deficiency (PKD) Natural History Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02053480
• Other study ID #: P00010515
• Status: Completed
• Start date: December 2013
• Est. completion date: May 2020

Study information

• Verified date: May 2020
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. The study will collect retrospective medical history, routine clinical care data, and quality of life measures at baseline and annually for patients with PKD.

Description:

The purpose of the Pyruvate Kinase Deficiency (PKD) Natural History Study is to describe the natural history of PKD and the range and incidence of symptoms, treatments, and complications related to PKD. The study will collect retrospective medical history and routine clinical care data at baseline and annually for patients with PKD. Patients without a genetic diagnosis will have a blood sample drawn for genetic diagnostic confirmation for research purposes. Understanding the clinical variation among participants with PKD, and assessing treatments specific to PKD and their outcomes will accelerate improvement in the care of patients with PKD. Understanding the natural history of PKD may be useful in the design of future interventional studies. Detailed genotypic and phenotypic characterization of the cohort will allow for continued in depth characterization of PKD. Finally, the PKD Natural History Study will identify interested participants for future PKD studies.

Primary Objectives:

1. To estimate the transfusion burden in splenectomized and non-splenectomized participants with PKD.

2. To establish a patient registry as a potential source for recruitment to future research studies in PKD.

Secondary Objectives:

1. To determine if patient-reported outcomes, including quality of life and fatigue scales, are associated with age, genotype, hemoglobin nadir, and/or transfusion burden, overall and within the subgroups of splenectomized vs. non-splenectomized participants;

2. To describe changes over time in the range of hemoglobin values and markers of hemolysis within individual participants and among participants with PKD;

3. To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment for PKD;

4. To estimate the prevalence and severity and describe the treatment of hepatic and cardiac iron overload and its complications in PKD (liver, cardiac, growth defects, hypogonadotropic hypogonadism, and other endocrine defects). To describe the changes in these complications that may occur over time and by age group;

5. To estimate the prevalence of co-morbidities associated with chronic hemolysis in PKD, to identify which co-morbidities are the most common, and to determine if the prevalence and/or severity of co-morbidities change over time and by age at the time of the first appearance of the co-morbidity;

6. To determine pregnancy outcomes among participants with PKD;

7. To describe genotypic and phenotypic variation among participants and explore genotype-phenotype correlation in PKD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: May 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients of all ages with biochemically or genetically diagnosed PKD.

• Patients with a hemolytic anemia AND a family member with genetically diagnosed PKD

• The participant or the guardian of the participant is willing and able to give written informed consent and/or assent.

Exclusion Criteria:

• The participant or the guardian of the participant is unwilling or unable to give written informed consent and/or assent.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Congenital Non-Spherocytic Hemolytic Anemia
• Hemolysis
• Pyruvate Kinase Deficiency

Locations

Country	Name	City	State
Canada	McMaster University	Hamilton	Ontario
Canada	CHU Sainte-Justine	Montreal	Quebec
Canada	University Health Network	Toronto	Ontario
Czechia	Fakultni Nemocnice Olomouc	Olomouc
Germany	Charite Berlin	Berlin
Germany	University of Freiburg	Freiburg
Germany	UniversitätsKlinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin Klinik Kinderheilkunde III	Heidelberg
Germany	Klinikum Kassel	Kassel
Germany	Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology	Munich
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milan
Netherlands	UMC Utrecht	Utrecht
United States	Children's Hospital of Atlanta	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of Vermont College of Medicine & University of Vermont Medical Center	Burlington	Vermont
United States	Lurie Children's Hospital	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospitals & Clinics	Kansas City	Missouri
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	DDC Clinic for Special Needs Children	Middlefield	Ohio
United States	Weill Cornell Medical College	New York	New York
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Utah	Salt Lake City	Utah
United States	Central Pennsylvania Clinic	Strasburg	Pennsylvania
United States	University of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children’s Hospital	Agios Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Italy,  Netherlands, 

References & Publications (3)

Bianchi P, Fermo E, Lezon-Geyda K, van Beers EJ, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al-Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020 May;95(5):472-482. doi: 10.1002/ajh.25753. Epub 2020 Mar 6. — View Citation

Grace RF, Bianchi P, van Beers EJ, Eber SW, Glader B, Yaish HM, Despotovic JM, Rothman JA, Sharma M, McNaull MM, Fermo E, Lezon-Geyda K, Morton DH, Neufeld EJ, Chonat S, Kollmar N, Knoll CM, Kuo K, Kwiatkowski JL, Pospíšilová D, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Kunz J, Sheth S, Rose MJ, Bradeen HA, Neu N, Guo D, Al-Sayegh H, London WB, Gallagher PG, Zanella A, Barcellini W. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018 May 17;131(20):2183-2192. doi: 10.1182/blood-2017-10-810796. Epub 2018 Mar 16. — View Citation

van Beers EJ, van Straaten S, Morton DH, Barcellini W, Eber SW, Glader B, Yaish HM, Chonat S, Kwiatkowski JL, Rothman JA, Sharma M, Neufeld EJ, Sheth S, Despotovic JM, Kollmar N, Pospíšilová D, Knoll CM, Kuo K, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Verhovsek M, Kunz J, McNaull MA, Rose MJ, Bradeen HA, Addonizio K, Li A, Al-Sayegh H, London WB, Grace RF. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019 Feb;104(2):e51-e53. doi: 10.3324/haematol.2018.196295. Epub 2018 Sep 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	transfusion burden in splenectomized and non-splenectomized participants		12 weeks
Secondary	patient-reported outcomes	EuroQoL-5D-5L, Functional Assessment of Cancer Therapy-Anemia (FACT-An), Pediatric Quality of Life Inventory 4.0 (pedsQL 4.0), Pediatric Functional Assessment of Chronic Illness-Fatigue (pedsFACIT-F), Patient Reported Outcomes Measurement Information System Fatigue (PROMIS Fatigue)	enrollment, annually, up to 2 years
Secondary	changes over time in hemoglobin and markers of hemolysis		enrollment, annually, up to 2 years
Secondary	prevalence and severity of iron overload		enrollment, annually, up to 2 years