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A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia

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: NCT03271541
Recruitment Status : Completed
First Posted : September 5, 2017
Last Update Posted : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:

This proof-of-mechanism study is being performed to investigate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of multiple oral doses of bitopertin in adults with NTD beta-thalassemia.

This study consists of two parts:

Part 1 - The main study - 16 weeks in total: Participants will undergo a 6-week dose-escalation period followed by 10 weeks of treatment at the attained target dose.

Part 2 - Open Label Extension (OLE) - up to an additional 12 months. Participants will be given the option to enroll into the OLE once the 16-week treatment of Part 1 has been completed. Participants who decide not to enroll in the OLE, at the end of Part 1 will enter a 6-week follow-up period.


Condition or disease Intervention/treatment Phase
Beta-Thalassemia Drug: Bitopertin Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single Arm, Multicenter, Proof-of-Mechanism Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent Βeta-Thalassemia
Actual Study Start Date : October 26, 2017
Actual Primary Completion Date : June 29, 2018
Actual Study Completion Date : June 29, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Bitopertin

Part 1 - The main study - 16 weeks in total:

Participants will undergo a 6-week dose-escalation period followed by 10 weeks of treatment at the attained target dose of bitopertin.

Part 2 - Open Label Extension (OLE) - up to an additional 12 months:

Participants will be given the option to enroll into the OLE once the 16-week treatment of Part 1 has been completed.

Participants who decide not to enroll in the OLE, at the end of Part 1 will enter a 6-week follow-up period.

 Drug: Bitopertin
Bitopertin will be administered orally once daily at doses up to 120 milligrams (mg).
Other Name: RO4917838


Outcome Measures
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Primary Outcome Measures :
  1. Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only [ Time Frame: Baseline, Week 16, up to Week 22 ]
  2. Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1 [ Time Frame: Baseline to Week 16 ]
  3. Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only [ Time Frame: Baseline to 19 Months ]

Secondary Outcome Measures :
  1. Apparent Clearance of Bitopertin [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  2. Volume of Distribution of Bitopertin [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  3. Area Under the Concentration-Time Curve (AUC) of Bitopertin within a Dosing Interval [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  4. Minimum Observed Concentration (Cmin) of Bitopertin [ Time Frame: Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113; and at early withdrawal (up to 22 weeks overall). Part 2: Predose (0 H) and postdose (1, 4 H) on Days 183, 365; and at early withdrawal (up to 65 weeks overall) ]
  5. Maximum Observed Concentration (Cmax) of Bitopertin [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  6. Apparent Elimination Half-Life of Bitopertin [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  7. Accumulation Ratio of Bitopertin [ Time Frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks ]
  8. Change from Baseline in Absolute Reticulocyte Count [ Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65 ]
  9. Change from Baseline in Serum Lactate Dehydrogenase Level [ Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65 ]
  10. Change from Baseline in Serum Bilirubin Level [ Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65 ]
  11. Change from Baseline in Absolute Red Blood Cell Count [ Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65 ]
  12. Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2 [ Time Frame: Baseline, 19 Months ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of beta-thalassemia
  • Clinically defined non-transfusion-dependent anemia (Part 1 only), defined as Hb concentrations >7.5 grams per deciliter (g/dL) and <9.5 g/dL, less than or equal to 4 transfusions of red blood cell units within 1 year prior to study enrollment, and no transfusion within 12 weeks prior to study enrollment
  • Completion of 16 weeks of treatment with bitopertin in Part 1 of this study with more than 80% compliance from expected use of study medication (based on patient diary and study drug accountability; Part 2 only)
  • A favorable benefit-risk ratio from treatment with bitopertin as assessed by the Investigator (Part 2 only)

Exclusion Criteria:

  • Any history of gene therapy
  • History of hemolytic anemia except for beta-thalassemia
  • Severe symptomatic splenomegaly and/or hepatomegaly with hypersplenism (Part 1 only)
  • Any use of an erythropoiesis-stimulating agent within 24 weeks prior to enrollment.
  • Initiation of iron chelation therapy or hydroxyurea within 24 weeks prior to enrollment (Part 1 only)
  • Depression, treatment with anti-depressants, or other psychiatric illnesses and/or drug abuse
  • Clinically significant/uncontrolled comorbid disease
  • Pregnant or breastfeeding females
  • Use of cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks or CYP3A4 inducers within 4 weeks prior to study drug
  • Active hepatitis B or C or known positive human immunodeficiency virus (HIV) test result
  • Diagnosis of cancer within previous 5 years unless treatment has resulted in complete freedom from disease for at least 2 years
  • Any major illness within 1 month or febrile illness within 1 week prior to study drug
  • Pulmonary hypertension requiring oxygen therapy (Part 1 only)
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): NCT03271541


Locations
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Italy
Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia
Genova, Liguria, Italy, 16128
Ospedale Maggiore di Milano; Cardio-Metabolic Diseases
Milano, Lombardia, Italy, 20122
Lebanon
Chronic Care Center
Baabda, Lebanon, 1003
Thailand
Siriraj Hospital; Division of Haematology-Oncology
Bangkok Noi, Thailand, 10700
Sponsors and Collaborators
Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03271541    
Other Study ID Numbers: BP39642
2016-004799-23 ( EudraCT Number )
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
 Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn