Beta-ThalassemiaPhase 2NCT03271541
A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
A Phase 2 study testing Bitopertin in people with Beta-Thalassemia, run by Hoffmann-La Roche at 4 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Beta-Thalassemia
- What is being tested?
- Bitopertin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 26 Oct 2017to 29 Jun 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 13Show fewer
- 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)
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Italy2 sites
Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia
Genoa, Liguria, 16128
Ospedale Maggiore di Milano; Cardio-Metabolic Diseases
Milan, Lombardy, 20122
Thailand1 site
Siriraj Hospital; Division of Haematology-Oncology
Bangkok Noi, 10700
About this study
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
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:
Read more
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.
- Conditions
- Beta-Thalassemia
- Being tested
- Bitopertin
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BitopertinDrug
Also called RO4917838
Bitopertin will be administered orally once daily at doses up to 120 milligrams (mg).
| Study group | Role | What they receive |
|---|---|---|
| Bitopertin | Experimental | 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. Receives: Drug: Bitopertin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only
Measured: Baseline, Week 16, up to Week 22
Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1
Measured: Baseline to Week 16
Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only
Measured: Baseline to 19 Months
Secondary outcomes (12)
Apparent Clearance of Bitopertin
Measured: 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
Volume of Distribution of Bitopertin
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Accumulation Ratio of Bitopertin
Measured: 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
Measured: Part 1: Baseline, Week 16. Part 2: Up to Week 65
Change from Baseline in Serum Lactate Dehydrogenase Level
Measured: Part 1: Baseline, Week 16. Part 2: Up to Week 65
Change from Baseline in Serum Bilirubin Level
Measured: Part 1: Baseline, Week 16. Part 2: Up to Week 65
Change from Baseline in Absolute Red Blood Cell Count
Measured: 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
Measured: Baseline, 19 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2017
- Study start26 Oct 2017
- Primary completion29 Jun 2018
- Study completion29 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03271541
- Sponsor's protocol ID
- BP39642
- Other IDs
- 2016-004799-23, 2016
- Status last verified
- Oct 2018
- First submitted
- 1 Sep 2017
- Last updated
- 5 Oct 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33931857
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03271541
- Acronym / sponsor ID
- BP39642
- Conditions
- Beta-Thalassemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2017 (actual)
- Primary completion
- 29 Jun 2018 (actual)
- Study completion
- 29 Jun 2018 (actual)
- First posted
- 5 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bitopertin | Experimental | Drug: BitopertinPart 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BitopertinAlso: RO4917838Bitopertin will be administered orally once daily at doses up to 120 milligrams (mg). | Drug | Bitopertin |
Primary outcome
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only
Time frame: Baseline, Week 16, up to Week 22
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
Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only
Time frame: Baseline to 19 Months
12 secondary outcomes
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
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
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 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
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
Change from Baseline in Absolute Reticulocyte Count
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 Serum Bilirubin 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2018.
- Derived from this study: PubMed 33931857Taher 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bitopertin in people with Beta-Thalassemia, run by Hoffmann-La Roche at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy, Lebanon, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only (time frame: Baseline, Week 16, up to Week 22). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03271541, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2018.