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Trial record 5 of 8 for:    Pyruvate Kinase Deficiency

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

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ClinicalTrials.gov Identifier: NCT03853798
Recruitment Status : Recruiting
First Posted : February 26, 2019
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE February 22, 2019
First Posted Date  ICMJE February 26, 2019
Last Update Posted Date February 6, 2020
Actual Study Start Date  ICMJE March 21, 2019
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From baseline to safety follow-up (up to 198 weeks) ]
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From baseline to end of study (Week 200) ]
  • Number of Participants with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation [ Time Frame: From baseline to end of study (Week 200) ]
Change History Complete list of historical versions of study NCT03853798 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • Change from Baseline in Hb Concentration [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Bilirubin [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Lactate Dehydrogenase (LDH) [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Haptoglobin Levels [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Reticulocyte Percentages [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Number of Transfusion Events [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused [ Time Frame: From baseline up to Week 193 (Day 1) ]
  • 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) ]
  • Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) [ Time Frame: From baseline up to Week 193 (Day 1) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • Change from Baseline in Hb Concentration [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Bilirubin [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Lactate Dehydrogenase (LDH) [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Haptoglobin Levels [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Reticulocyte Percentages [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Number of Transfusion Events [ Time Frame: From baseline up to Week 193 ]
  • Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused [ Time Frame: From baseline up to Week 193 ]
  • 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 ]
  • Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) [ Time Frame: From baseline up to Week 193 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
Official Title  ICMJE An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pyruvate Kinase Deficiency
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.

    Intervention: Drug: AG-348
  • 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.

    Intervention: Drug: AG-348
  • 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.

    Intervention: Drug: AG-348
Publications * Rab MAE, van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, van Straaten S, van Solinge WW, van Beers EJ, Kung C, van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2020 Jan 23. pii: haematol.2019.238865. doi: 10.3324/haematol.2019.238865. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2019)
116
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2019)
96
Estimated Study Completion Date  ICMJE January 2025
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Affairs 833-228-8474 medinfo@agios.com
Listed Location Countries  ICMJE Brazil,   Canada,   Czechia,   Denmark,   France,   Germany,   Ireland,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Portugal,   Spain,   Switzerland,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03853798
Other Study ID Numbers  ICMJE AG348-C-011
2018-003459-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Agios Pharmaceuticals, Inc.
Study Sponsor  ICMJE Agios Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Medical Affairs Agios Pharmaceuticals, Inc.
PRS Account Agios Pharmaceuticals, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP