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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03271541
Other study ID # BP39642
Secondary ID 2016-004799-23
Status Completed
Phase Phase 2
First received
Last updated
Start date October 26, 2017
Est. completion date June 29, 2018

Study information

Verified date October 2018
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date June 29, 2018
Est. primary completion date June 29, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 55 Years
Eligibility 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)

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Italy Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia Genova Liguria
Italy Ospedale Maggiore di Milano; Cardio-Metabolic Diseases Milano Lombardia
Lebanon Chronic Care Center Baabda
Thailand Siriraj Hospital; Division of Haematology-Oncology Bangkok Noi

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Italy,  Lebanon,  Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only Baseline, Week 16, up to Week 22
Primary Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1 Baseline to Week 16
Primary Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only Baseline to 19 Months
Secondary Apparent Clearance of Bitopertin 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
Secondary Volume of Distribution of Bitopertin 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
Secondary Area Under the Concentration-Time Curve (AUC) of Bitopertin within a Dosing Interval 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
Secondary Minimum Observed Concentration (Cmin) of Bitopertin 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)
Secondary Maximum Observed Concentration (Cmax) of Bitopertin 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
Secondary Apparent Elimination Half-Life of Bitopertin 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
Secondary Accumulation Ratio of Bitopertin 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
Secondary Change from Baseline in Absolute Reticulocyte Count Part 1: Baseline, Week 16. Part 2: Up to Week 65
Secondary Change from Baseline in Serum Lactate Dehydrogenase Level Part 1: Baseline, Week 16. Part 2: Up to Week 65
Secondary Change from Baseline in Serum Bilirubin Level Part 1: Baseline, Week 16. Part 2: Up to Week 65
Secondary Change from Baseline in Absolute Red Blood Cell Count Part 1: Baseline, Week 16. Part 2: Up to Week 65
Secondary Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2 Baseline, 19 Months
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