Clinical Trial Results:
Interventional, Open-Label, Flexible-Dose, Long-Term Safety Extension Study of Lu AF11167 in Patients with Schizophrenia
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Summary
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EudraCT number |
2018-002708-15 |
Trial protocol |
LV BG DE PL CZ |
Global end of trial date |
14 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Sep 2021
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First version publication date |
11 Sep 2021
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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 |
17972B
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03929497 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
H. Lundbeck A/S
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Sponsor organisation address |
Otilliavej 9, Valby, Denmark, 2500
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Public contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
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Scientific contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.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 |
14 Sep 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Sep 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Sep 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of the trial was to evaluate the long-term safety and tolerability of doses (2 or 4 milligrams [mg]/day) of Lu AF11167 in participants with schizophrenia during the 24-week treatment period.
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Protection of trial subjects |
This study was conducted in compliance with Good Clinical Practice.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Apr 2019
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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 |
Bulgaria: 41
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Country: Number of subjects enrolled |
Estonia: 14
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Hungary: 4
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Ukraine: 33
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Worldwide total number of subjects |
96
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EEA total number of subjects |
63
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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) |
96
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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 |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
This is a flexible-dose extension study in participants with schizophrenia who had participated and completed Study 17972A (NCT03793712, EudraCT number: 2018-001581-42). The study design included a 24-week Open-Label Treatment Period and a 2-week Safety Follow-up Period. | ||||||||||||||||||
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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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Lu AF11167 2 or 4 mg/day | ||||||||||||||||||
Arm description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. Based on the investigator’s clinical judgement, the dose was increased to 4 mg/day. If this dose was not tolerated, the dose was reduced to 2 mg/day once daily at any time during the study. Total treatment duration was 24 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Lu AF11167
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Modified-release tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lu AF11167 was administered per dose and schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Lu AF11167 2 or 4 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. Based on the investigator’s clinical judgement, the dose was increased to 4 mg/day. If this dose was not tolerated, the dose was reduced to 2 mg/day once daily at any time during the study. Total treatment duration was 24 weeks. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lu AF11167 2 or 4 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. Based on the investigator’s clinical judgement, the dose was increased to 4 mg/day. If this dose was not tolerated, the dose was reduced to 2 mg/day once daily at any time during the study. Total treatment duration was 24 weeks. | ||
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End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [1] | ||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product and which did not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavourable and unintended sign (including clinically significant out-of-range values from relevant tests, such as clinical safety laboratory tests, vital signs, electrocardiograms [ECGs]), symptom, or disease temporally associated with the use of a medicinal product, regardless of whether it was considered related to the medicinal product. TEAE was an AE that started or increased in intensity on or after the date of first dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. All-patients-treated set (APTS) included all enrolled participants who took at least 1 dose of Lu AF11167 in Study 17972B.
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End point type |
Primary
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End point timeframe |
Baseline (Day 0) up to Week 26
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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: The analysis was descriptive in nature. |
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| No statistical analyses for this end point | |||||||
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End point title |
Change From Baseline in Brief Negative Symptom Scale (BNSS) Total Score at Week 24 | ||||||||
End point description |
The BNSS is a brief clinician rating scale, intended to measure negative symptoms. It consists of 13 items organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect, and alogia. The items score the impairment. Items 1 to 4 were rated from 0 (Normal) to 6 (Extremely severe) and items 5 to 13 were rated from 0 (No impairment) to 6 (Severe deficit). The BNSS total score was calculated by summing the 13 individual items. The BNSS total scores range from 0 to 78. Full analysis set (FAS) included all enrolled participants who took at least 1 dose of the Lu AF11167 in Study 17972B and who had a valid baseline assessment and at least 1 valid post-baseline assessment of the BNSS total score. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Symptoms Factor Score at Week 24 | ||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). PANSS total score: sum of all items and ranges from 30 to 210. Subscale scores: sum of items within each subscale. FAS: all enrolled participants who took at least 1 dose of the Lu AF11167 in Study 17972B and who had a valid baseline and at least 1 valid post-baseline assessment of the BNSS total score. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in PANSS Negative Subscale Score at Week 24 | ||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders, and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). Subscale scores: sum of items within each subscale. FAS: all enrolled participants who took at least 1 dose of the Lu AF11167 in Study 17972B and who had a valid baseline and at least 1 valid post-baseline assessment of the BNSS total score. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Clinical Global Impression — Schizophrenia Severity of Illness (CGI-SCH-S) Negative Symptoms Score at Week 24 | ||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. The CGI-SCH severity of illness category symptoms and overall severity were rated on a 7-point scale ranging from 1 (normal - not ill) to 7 (among the most severely ill). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. FAS: all enrolled participants who took at least 1 dose of the Lu AF11167 in Study 17972B and who had a valid baseline and at least 1 valid post-baseline assessment of the BNSS total score. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Clinical Global Impression — Schizophrenia Degree of Change (CGI-SCH-DC) Negative Symptoms Score at Week 24 | ||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. In the CGI-SCH degree of change category symptoms and overall severity were rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. FAS: all enrolled participants who took at least 1 dose of the Lu AF11167 in Study 17972B and who had a valid baseline and at least 1 valid post-baseline assessment of the BNSS total score. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With a CGI-SCH-DC Negative Symptoms Response at Week 24 | ||||||
End point description |
CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both global illness severity and degree of change, CGI-SCH consists of 4 groups of symptoms (positive, negative, cognitive, and depressive) and overall severity of disorder. In CGI-SCH degree of change category symptoms and overall severity were rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. CGI-SCH-DC negative symptoms response defined as CGI-SCH-DC negative symptoms score of 1 or 2. FAS: all enrolled participants who took at least 1 dose of Lu AF11167 in Study 17972B and who had a valid baseline and at least 1 valid post-baseline assessment of BNSS total score. 'Overall number of participants analyzed'=participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 24
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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 (Day 0) up to Week 26
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Adverse event reporting additional description |
APTS included all enrolled participants who took at least 1 dose of Lu AF11167 in Study 17972B.
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Assessment type |
Non-systematic | ||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Lu AF11167 2 or 4 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. Based on the investigator’s clinical judgement, the dose was increased to 4 mg/day. If this dose was not tolerated, the dose was reduced to 2 mg/day once daily at any time during the study. Total treatment duration was 24 weeks. | ||||||||||||||||||||||
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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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21 Dec 2018 |
This amendment was prepared to update the heart-rate corrected QT interval using Fridericia’s correction formula (QTcF) withdrawal criteria, to update the Cogstate Schizophrenia Cognitive Battery and timepoint of Entry/Exit interviews, and to provide clarifications and corrections to the protocol. |
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11 May 2020 |
This amendment was prepared to add the United States as a participating country. |
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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 terminated based on the interim analysis for futility in the lead-in Study 17972A. | |||
