ICTRP Search Portal

Main

Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.

Register:	ClinicalTrials.gov
Last refreshed on:	12 December 2020
Main ID:	NCT03271541
Date of registration:	01/09/2017
Prospective Registration:	Yes
Primary sponsor:	Hoffmann-La Roche
Public title:	A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
Scientific 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 ?eta-Thalassemia
Date of first enrolment:	October 26, 2017
Target sample size:	12
Recruitment status:	Completed
URL:	https://clinicaltrials.gov/show/NCT03271541
Study type:	Interventional
Study design:	Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase:	Phase 2

Countries of recruitment
Italy	Lebanon	Thailand

Contacts

Key inclusion & exclusion 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)

Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Beta-Thalassemia

Intervention(s)

Drug: Bitopertin

Primary Outcome(s)

Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only [Time Frame: Baseline, Week 16, up to Week 22]

Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only [Time Frame: Baseline to 19 Months]

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]

Secondary Outcome(s)

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]

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]

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)]

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]

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]

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]

Change from Baseline in Serum Bilirubin Level [Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65]

Change from Baseline in Serum Lactate Dehydrogenase Level [Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65]

Change from Baseline in Absolute Red Blood Cell Count [Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65]

Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2 [Time Frame: Baseline, 19 Months]

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]

Change from Baseline in Absolute Reticulocyte Count [Time Frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65]

Secondary ID(s)

2016-004799-23

BP39642

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ethics review

Results

Results available:
Date Posted:
Date Completed:
URL:

Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.