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Trial record 2 of 13 for:    AG-348

A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia

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ClinicalTrials.gov Identifier: NCT03692052
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief Summary:
Study AG348-C-010 is a multicenter study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of treatment with AG-348 in adult participants with non-transfusion-dependent thalassemia (NTDT). This study will include a 24-week core period followed by a 2-year extension period for eligible participants. Approximately 17 participants with NTDT will be enrolled. The initial dose of AG-348 will be 50 milligrams (mg) twice daily (BID) with one potential dose-level increase to 100 mg BID, at the Week 6 visit based on the participant's safety and hemoglobin (Hb) concentrations.

Condition or disease Intervention/treatment Phase
Thalassemia Drug: AG-348 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Multicenter Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Subjects With Non-transfusion-dependent Thalassemia
Actual Study Start Date : December 28, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arm Intervention/treatment
Experimental: AG-348

Core period: Participants will receive AG-348 for up to 24 weeks. Depending on the safety observations and hemoglobin (Hb) concentrations, they may undergo one potential dose-level increase from 50 to 100 mg BID.

Extension Period: Eligible participants will continue to receive AG-348 for up to 2 years at the same dose they were receiving at the Week 24 visit.

Drug: AG-348

Core period: Participants will receive an initial AG-348 dose of 50 mg BID, oral tablets, and may undergo one potential dose-level increase to 100 mg BID, based on an evaluation of the participant's safety profile and Hb concentrations.

Extension Period: Participants who achieve a Hb response with an acceptable safety profile will continue receiving treatment with AG-348 for up to 2 years at the same dose they were receiving at the Week 24 Visit.





Primary Outcome Measures :
  1. Percentage of Participants Achieving a Hemoglobin Response (HR) [ Time Frame: Up to 12 weeks ]
    HR is defined as a ≥1.0 gram per deciliter (g/dL) increase in Hb concentration from baseline at 1 or more assessments between Week 4 and Week 12 (inclusive). A participant's baseline Hb concentration is defined as the average of all the participant's available Hb concentrations during the 42-day screening period up to the first dose of study drug.


Secondary Outcome Measures :
  1. Mean Change from Baseline in Hb Concentrations from Week 12 to Week 24 [ Time Frame: Baseline, Week 12 to Week 24 ]
  2. Percentage of Participants Achieving a Sustained Hb Response (sHR) [ Time Frame: Week 12 to Week 24 ]
    sHR is defined as a ≥1.0 g/dL increase in Hb concentration at 2 or more evaluable Hb assessments out of the 4 scheduled assessments between the Week 12 Visit and Week 24 Visit

  3. Change from Baseline in Hb Concentration over an Additional 2 Years in the Extension Period [ Time Frame: Baseline up to approximately 2.5 years ]
  4. Time to Achieve HR [ Time Frame: Up to approximately 2.5 years ]
  5. Change from Baseline in Reticulocyte Count [ Time Frame: Up to approximately 2.5 years ]
  6. Change from Baseline in Bilirubin [ Time Frame: Up to approximately 2.5 years ]
  7. Change from Baseline in Lactate Dehydrogenase (LDH) [ Time Frame: Up to approximately 2.5 years ]
  8. Change from Baseline in Haptoglobin [ Time Frame: Up to approximately 2.5 years ]
  9. Change from Baseline in Nucleated Red Blood Cells (NRBCs) [ Time Frame: Up to approximately 2.5 years ]
  10. Change from Baseline in Erythropoietin (EPO) [ Time Frame: Up to approximately 2.5 years ]
  11. Change from Baseline in Soluble Transferrin Receptor [ Time Frame: Up to approximately 2.5 years ]
  12. Drug Concentrations over Time for AG-348 [ Time Frame: Pre-dose at Weeks 1, 2, 3, 4, 6, 8, 16, 20, and 24 ]
  13. Percentage of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Significant Interest (AESIs), and AEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation [ Time Frame: Up to approximately 2.5 years ]


Information from the National Library of Medicine

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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:

  • Informed consent;
  • Be aged 18 years or older;
  • Known medical history of thalassemia, including β-thalassemia intermedia, Hb E β-thalassemia, α-thalassemia (Hb H disease), or β-thalassemia with mutations of 1 or more α genes;
  • Documented clinical laboratory confirmation of thalassemia by Hb electrophoresis/high-performance liquid chromatography (HPLC) or deoxyribonucleic acid (DNA) analysis, either from medical records or during the screening period;
  • Hb concentration ≤9.0 grams per deciliter (g/dL), regardless of sex, based on an average of at least 2 Hb measurements (separated by a minimum of 7 days) during the screening period;
  • Considered non-transfusion-dependent, defined as having no more than 5 units of red blood cells (RBCs) transfused during the 24-week period up to the first day of study drug and no RBC transfusions in the 8 weeks prior to the first day of study drug;
  • Have adequate organ function;
  • For women of reproductive potential: negative serum pregnancy test during the screening period and a negative serum or urine pregnancy test on Day 1;
  • For women of reproductive potential as well as men with partners who are women of reproductive potential: abstinent as part of their usual lifestyle, or agreement 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 (both men and women) following the last dose of study drug;
  • Willingness to comply with all study procedures for the duration of the study;

Exclusion Criteria:

  • Known history of diagnosis of Hb S or Hb C forms of thalassemia;
  • Significant medical condition that confers an unacceptable risk to participating in the study, and/or could confound the interpretation of the study data;
  • Splenectomy scheduled during the study treatment period or having undergone splenectomy within 12 months prior to signing informed consent;
  • Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo;
  • Exposure to any investigational drug, device, or procedure within 3 months prior to the first day of study drug;
  • Prior exposure to sotatercept (ACE-011), luspatercept (ACE-536), ruxolitinib, or gene therapy;
  • Prior bone marrow or stem cell transplant;
  • Currently pregnant or breastfeeding;
  • History of major surgery within 6 months of signing informed consent;
  • 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 the first day of study drug;
  • Currently receiving chronic anticoagulant therapy, unless started and on a stable dose for at least 28 days prior to first day of study drug;
  • Currently receiving anabolic steroids, including testosterone preparations, if initiated ≤28 days prior to the first day of study drug;
  • Currently receiving hematopoietic stimulating agents (e.g., erythropoietins, granulocyte colony stimulating factors, thrombopoietins), if initiated ≤8 weeks prior to the first day of study drug;
  • History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations;
  • History of allergy to AG-348 or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, and mannitol).

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): NCT03692052


Contacts
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Contact: Medical Affairs 833-228-8474 medinfo@agios.com

Locations
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United States, California
UCSF Benioff Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Canada, Ontario
University Health Network (Toronto General Hospital) Recruiting
Toronto, Ontario, Canada, M5G 2C4
United Kingdom
Imperial College Healthcare NHS Trust (Hammersmith Hospital) Recruiting
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
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Study Chair: Medical Affairs Agios Pharmaceuticals, Inc.

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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03692052     History of Changes
Other Study ID Numbers: AG348-C-010
2018‐002217‐35 ( EudraCT Number )
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019

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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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Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn