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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03853798
Recruitment Status : Active, not recruiting
First Posted : February 26, 2019
Last Update Posted : May 25, 2023
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Pyruvate Kinase Deficiency Drug: AG-348 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies
Actual Study Start Date : March 21, 2019
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1

Participants who received placebo in Study AG348-C-006 will enroll in Cohort 1.

Part 1 (Dose Optimization Period, 12 weeks): Participants will begin by receiving 5 milligrams (mg) orally, twice a day. Each participant's dose of AG-348 may be increased to 20 mg twice a day and then to 50 mg twice a day depending on their response to AG-348 and tolerability.

Part 2 (Fixed Dose Period, 12 weeks): Last dose received in Part 1, twice a day.

After completion of Part 2, participants who, in the opinion of the Investigator, have demonstrated clinical benefit from AG-348 treatment will continue AG-348 treatment in the Continued Treatment Period.

 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.
Experimental: Cohort 2

Participants who received AG-348 in Study AG348-C-006 will enroll in Cohort 2.

Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-006.

 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.
Experimental: Cohort 3

Participants who received AG-348 in Study AG348-C-007 will enroll in Cohort 3.

Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-007.

 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.


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From baseline to safety follow-up (up to 198 weeks) ]
  2. Number of Participants with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation [ Time Frame: From baseline to safety follow-up (up to 198 weeks) ]

Secondary Outcome Measures :
  1. Percentage of Participants Achieving a Hemoglobin (Hb) Response in Participants Who Previously Received Placebo in Study AG348-C-006 [ Time Frame: Weeks 16, 20, 24 ]
  2. Area Under the Concentration-Time Curve (AUC) of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 [ Time Frame: Week 12: pre-dose, post-dose at 30 minutes, 1 hour (h), 2 h, 4 h, 8 h ]
  3. Maximum Observed Concentration of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 [ Time Frame: Week 12: pre-dose, post-dose at 30 minutes, 1 h, 2 h, 4 h, 8 h ]
  4. Change from Baseline in Hb Concentration [ Time Frame: From baseline up to Week 193 (Day 1) ]
  5. Change from Baseline in Bilirubin [ Time Frame: From baseline up to Week 193 (Day 1) ]
  6. Change from Baseline in Lactate Dehydrogenase (LDH) [ Time Frame: From baseline up to Week 193 (Day 1) ]
  7. Change from Baseline in Haptoglobin Levels [ Time Frame: From baseline up to Week 193 (Day 1) ]
  8. Change from Baseline in Reticulocyte Percentages [ Time Frame: From baseline up to Week 193 (Day 1) ]
  9. Change from Baseline in Number of Transfusion Events [ Time Frame: From baseline up to Week 193 (Day 1) ]
  10. Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused [ Time Frame: From baseline up to Week 193 (Day 1) ]
  11. Change from Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD) [ Time Frame: From baseline up to Week 193 (Day 1) ]
  12. Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) [ Time Frame: From baseline up to Week 193 (Day 1) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03853798


Locations
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Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
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Study Chair: Medical Affairs Agios Pharmaceuticals, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03853798    
Other Study ID Numbers: AG348-C-011
2018-003459-39 ( EudraCT Number )
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: May 25, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Hemolytic, Congenital Nonspherocytic
Pyruvate Metabolism, Inborn Errors
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
 Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Mitapivat
Enzyme Activators
Molecular Mechanisms of Pharmacological Action