Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007

Pyruvate Kinase Deficiency Clinical Trial

Official title:

An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03853798
• Other study ID #: AG348-C-011
• Secondary ID: 2018-003459-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 21, 2019
• Est. completion date: June 2024

Study information

• Verified date: June 2024
• Source: Agios Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with AG-348 in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be willing and able to comply with study visits and procedures;

• Have signed written informed consent prior to participating in this extension study;

• Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit;

• Cohorts 2 and 3: Have demonstrated clinical benefit from AG-348 treatment in the antecedent study, in the opinion of the Investigator;

• For women of reproductive potential, have a negative pregnancy test during screening;

• For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men.

Exclusion Criteria:

• Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures.

• Are currently pregnant or breastfeeding.

• Have a splenectomy scheduled during the study treatment period.

• Meet the withdrawal criteria of his/her antecedent AG-348 study during screening of this extension study.

• Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study.

• Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study.

• Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study.

• Have exposure to any investigational drug other than AG-348, device, or procedure within 3 months prior to start of study drug on this extension study.

Related Conditions & MeSH terms

• Pyruvate Kinase Deficiency

Intervention

Drug:
• AG-348
Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.

Locations

Country	Name	City	State
Brazil	UNICAMP - Hemocentro	São Paulo
Canada	McMaster University	Hamilton	Ontario
Denmark	Herlev University Hospital	Herlev
France	CHU Hopitaux de Bordeaux - Hôpital Saint-André	Bordeaux
France	CHU Hôpital Henri Mondor	Créteil
France	Hospital La Timone	Marseille
France	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse
Germany	Charite - UB - CVK - Medizinische Klinik	Berlin
Germany	Universitätsklinik Würzburg	Würzburg
Ireland	St James's Hospital	Dublin 8
Italy	Ospedale Galliera	Genova
Italy	Osp Maggiore Policlinico Milano	Milano
Italy	AORN Cardarelli	Napoli
Italy	Università della Campania "Luigi Vanvitelli"	Napoli
Japan	Kyoto Katsura Hospital	Kyoto
Japan	Kansai Medical University, Dep. of Pediatrics, Hirakata Hospital	Osaka
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Toho University Omori Medical Center	Tokyo
Japan	Mie University Hospital	Tsu-shi	Mie
Korea, Republic of	Yeungnam University Hospital	Daegu
Netherlands	Van Creveldkliniek	Utrecht
Spain	Hospital. U. Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Htal Clínico Universitario Virgen de la Arrixaca.	Murcia
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Vaud (Lausanne)
Thailand	Faculty of Medicine Siriraj Hospital	Bangkok
Turkey	Hacettepe University Faculty of Medicine	Ankara
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	University College London	London
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Houston Methodist Research Institute	Houston	Texas
United States	Indiana Hemophilia & Thrombosis Center Inc.	Indianapolis	Indiana
United States	UCSF Benioff Children's Hospital, Oakland	Oakland	California
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Agios Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Denmark,  France,  Germany,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Switzerland,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		From baseline to safety follow-up (up to 198 weeks)
Primary	Number of Participants with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation		From baseline to safety follow-up (up to 198 weeks)
Secondary	Percentage of Participants Achieving a Hemoglobin (Hb) Response in Participants Who Previously Received Placebo in Study AG348-C-006		Weeks 16, 20, 24
Secondary	Area Under the Concentration-Time Curve (AUC) of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006		Week 12: pre-dose, post-dose at 30 minutes, 1 hour (h), 2 h, 4 h, 8 h
Secondary	Maximum Observed Concentration of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006		Week 12: pre-dose, post-dose at 30 minutes, 1 h, 2 h, 4 h, 8 h
Secondary	Change from Baseline in Hb Concentration		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Bilirubin		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Lactate Dehydrogenase (LDH)		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Haptoglobin Levels		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Reticulocyte Percentages		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Number of Transfusion Events		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD)		From baseline up to Week 193 (Day 1)
Secondary	Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA)		From baseline up to Week 193 (Day 1)