Back to resultsA Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
Primary Purpose
Beta-Thalassemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bitopertin
Sponsored by
About this trial
This is an interventional treatment trial for Beta-Thalassemia
Eligibility 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)
Sites / Locations
- Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia
- Ospedale Maggiore di Milano; Cardio-Metabolic Diseases
- Chronic Care Center
- Siriraj Hospital; Division of Haematology-Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bitopertin
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only
Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1
Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only
Secondary Outcome Measures
Apparent Clearance of Bitopertin
Volume of Distribution of Bitopertin
Area Under the Concentration-Time Curve (AUC) of Bitopertin within a Dosing Interval
Minimum Observed Concentration (Cmin) of Bitopertin
Maximum Observed Concentration (Cmax) of Bitopertin
Apparent Elimination Half-Life of Bitopertin
Accumulation Ratio of Bitopertin
Change from Baseline in Absolute Reticulocyte Count
Change from Baseline in Serum Lactate Dehydrogenase Level
Change from Baseline in Serum Bilirubin Level
Change from Baseline in Absolute Red Blood Cell Count
Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03271541
Brief Title
A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 26, 2017 (Actual)
Primary Completion Date
June 29, 2018 (Actual)
Study Completion Date
June 29, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta-Thalassemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bitopertin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bitopertin
Other Intervention Name(s)
RO4917838
Intervention Description
Bitopertin will be administered orally once daily at doses up to 120 milligrams (mg).
Primary Outcome Measure Information:
Title
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only
Time Frame
Baseline, Week 16, up to Week 22
Title
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
Title
Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only
Time Frame
Baseline to 19 Months
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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)
Title
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
Title
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
Title
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
Title
Change from Baseline in Absolute Reticulocyte Count
Time Frame
Part 1: Baseline, Week 16. Part 2: Up to Week 65
Title
Change from Baseline in Serum Lactate Dehydrogenase Level
Time Frame
Part 1: Baseline, Week 16. Part 2: Up to Week 65
Title
Change from Baseline in Serum Bilirubin Level
Time Frame
Part 1: Baseline, Week 16. Part 2: Up to Week 65
Title
Change from Baseline in Absolute Red Blood Cell Count
Time Frame
Part 1: Baseline, Week 16. Part 2: Up to Week 65
Title
Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2
Time Frame
Baseline, 19 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Facility Information:
Facility Name
Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia
City
Genova
State/Province
Liguria
ZIP/Postal Code
16128
Country
Italy
Facility Name
Ospedale Maggiore di Milano; Cardio-Metabolic Diseases
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
Chronic Care Center
City
Baabda
ZIP/Postal Code
1003
Country
Lebanon
Facility Name
Siriraj Hospital; Division of Haematology-Oncology
City
Bangkok Noi
ZIP/Postal Code
10700
Country
Thailand
12. IPD Sharing Statement
Citations:
PubMed Identifier
33931857
Citation
Taher AT, Viprakasit V, Cappellini MD, Kraus D, Cech P, Volz D, Winter E, Nave S, Dukart J, Khwaja O, Koerner A, Hermosilla R, Brugnara C. Haematological effects of oral administration of bitopertin, a glycine transport inhibitor, in patients with non-transfusion-dependent beta-thalassaemia. Br J Haematol. 2021 Jul;194(2):474-477. doi: 10.1111/bjh.17479. Epub 2021 Apr 30. No abstract available.
Results Reference
derived
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A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
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