Clinical Trial Results:
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 beta-Thalassemia
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Summary
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EudraCT number |
2016-004799-23 |
Trial protocol |
IT |
Global end of trial date |
29 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2019
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First version publication date |
06 Jul 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BP39642
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03271541 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jun 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jun 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This was a proof-of-mechanism study designed to investigate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of multiple oral doses of bitopertin in adults with non-transfusion-dependent (NTD) beta-thalassemia.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Oct 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Lebanon: 5
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Country: Number of subjects enrolled |
Thailand: 5
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Worldwide total number of subjects |
12
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at three centers in Italy, Lebanon, and Thailand. | ||||||||||||||
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Pre-assignment
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Screening details |
The study population consisted of male and female subjects between ages 18-55 (inclusive) with a confirmed diagnosis of NTD beta-thalassemia. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Bitopertin | ||||||||||||||
Arm description |
Subjects underwent 6 weeks of dose-escalation, followed by 10 weeks of treatment at the attained target dose of bitopertin, and 6 weeks of follow-up. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Bitopertin
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Investigational medicinal product code |
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Other name |
RO4917838
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received once-daily oral doses of bitopertin according to the following schedule: 30mg for Days 1-14, 60mg for Days 15-28, and 90mg for days 29-42.
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Baseline characteristics reporting groups
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Reporting group title |
Bitopertin
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Reporting group description |
Subjects underwent 6 weeks of dose-escalation, followed by 10 weeks of treatment at the attained target dose of bitopertin, and 6 weeks of follow-up. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bitopertin
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Reporting group description |
Subjects underwent 6 weeks of dose-escalation, followed by 10 weeks of treatment at the attained target dose of bitopertin, and 6 weeks of follow-up. | ||
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End point title |
Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only [1] | ||||||||
End point description |
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered adverse events.
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End point type |
Primary
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End point timeframe |
Baseline, Week 16, up to Week 22
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal hypothesis testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1 [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline to Week 16
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal hypothesis testing was performed. |
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| Notes [3] - Data from 12 subjects was available at baseline. Six subjects were analyzed at Week 16. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only [4] | ||||||||
End point description |
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered adverse events.
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End point type |
Primary
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End point timeframe |
Baseline to 19 Months
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal hypothesis testing was performed. |
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| Notes [5] - Part 2 was not conducted. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Pharmacokinetic Concentrations of Bitopertin | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [6] - n=12 for the first time point. For Days 15, 29, 57, 85, and 113, n=11, 12, 10, 11, and 6. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change from Baseline in Absolute Reticulocyte Count | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Baseline, Week 16
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| Notes [7] - Data from 12 subjects was available at baseline. Six subjects were analyzed at Week 16. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Serum Lactate Dehydrogenase Level | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Baseline, Week 16
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| Notes [8] - Data from 12 subjects was available at baseline. Six subjects were analyzed at Week 16. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Serum Bilirubin Level | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Baseline, Week 16
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| Notes [9] - Data from 12 subjects was available at baseline. Six subjects were analyzed at Week 16. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent Clearance of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [10] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of Distribution of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [11] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve (AUC) of Bitopertin within a Dosing Interval | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [12] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Minimum Observed Concentration (Cmin) of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [13] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Concentration (Cmax) of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [14] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Elimination Half-Life of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [15] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Accumulation Ratio of Bitopertin | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113
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| Notes [16] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Absolute Red Blood Cell Count | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Part 1: Baseline, Week 16.
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| Notes [17] - This OM was not reported due to study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline, 19 Months
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| Notes [18] - Part 2 was not conducted. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline through the end of study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Bitopertin
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Dec 2017 |
Added an open-label extension; added a new dose formulation; adjustment to ophthalmological assessments |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was prematurely terminated, and Part 2 was not conducted. | |||
