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    Clinical Trial Results:
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of NBI-921352 as Adjunctive Therapy in Adult Subjects with Focal Onset Seizures (FOS)

    Summary
    EudraCT number
    		 2021-001433-39
    Trial protocol
    		 CZ   HU   FR   IT   BE   ES  
    Global end of trial date
    21 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Sep 2024
    First version publication date
    06 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NBI-921352-FOS2021
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05159908
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Neurocrine Biosciences
    Sponsor organisation address
    12780 El Camino Real, San Diego, United States, 92130
    Public contact
    Neurocrine Medical Information, Neurocrine Biosciences Inc., +1 877-641-3461, medinfo@neurocrine.com
    Scientific contact
    Neurocrine Medical Information, Neurocrine Biosciences Inc., +1 877-641-3461, medinfo@neurocrine.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Mar 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Aug 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to assess the safety and tolerability and to characterize the pharmacokinetic (PK) and PK/pharmacodynamic (PD) relationship of NBI-921352 in adults with FOS taking concomitant background antiseizure medications (ASMs).
    Protection of trial subjects
    This study was performed in full compliance with applicable Good Clinical Practice (GCP) and regulations, including the archiving of essential documents.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Nov 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 30
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Czechia: 36
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Australia: 10
    Worldwide total number of subjects
    101
    EEA total number of subjects
    91
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    101
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were randomized 1:1:1:1 to placebo, NBI-921352 low, medium, or high dose groups to achieve target doses during maintenance period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received matching placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to NBI-921352 was administered.

    Arm title
    		 NBI-921352 Low Dose
    Arm description
    		 Participants received NBI-921352 low dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NBI-921352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    NBI-921352 was administered.

    Arm title
    		 NBI-921352 Medium Dose
    Arm description
    		 Participants received NBI-921352 medium dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NBI-921352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    NBI-921352 was administered.

    Arm title
    		 NBI-921352 High Dose
    Arm description
    		 Participants received NBI-921352 high dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NBI-921352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    NBI-921352 was administered.

    Number of subjects in period 1
    		Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Started
    26
    25
    25
    25
    Received at Least 1 Dose of Study Drug
    26
    25
    25
    25
    Completed
    24
    22
    22
    22
    Not completed
    2
    3
    3
    3
         Consent withdrawn by subject
    -
    1
    -
    1
         Adverse event, non-fatal
    1
    2
    3
    2
         Other than specified
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo.

    Reporting group title
    NBI-921352 Low Dose
    Reporting group description
    		 Participants received NBI-921352 low dose.

    Reporting group title
    NBI-921352 Medium Dose
    Reporting group description
    		 Participants received NBI-921352 medium dose.

    Reporting group title
    NBI-921352 High Dose
    Reporting group description
    		 Participants received NBI-921352 high dose.

    Reporting group values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose Total
    Number of subjects
    		 26 25 25 25 101
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 46.0 ( 10.8 ) 38.8 ( 10.0 ) 42.0 ( 12.0 ) 41.5 ( 11.0 ) -
    Gender categorical
    Units: Subjects
        Female
    		 13 15 13 10 51
        Male
    		 13 10 12 15 50
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 5 3 4 3 15
        Not Hispanic or Latino
    		 21 22 21 22 86
    Race
    Units: Subjects
        Asian
    		 0 1 0 0 1
        White
    		 25 22 23 20 90
        Other
    		 0 1 0 2 3
        Not collected
    		 1 1 2 3 7
    28-Day Focal onset Seizure (FOS) Frequency
    Baseline 28-day FOS frequency was calculated as: 28 × Total number of FOS during the baseline period/Total number of days in the baseline period with non-missing diary data.
    Units: seizures per 28 days
        arithmetic mean (standard deviation)
    		 17.63 ( 12.87 ) 14.56 ( 15.91 ) 28.54 ( 38.42 ) 32.59 ( 53.42 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo.

    Reporting group title
    NBI-921352 Low Dose
    Reporting group description
    		 Participants received NBI-921352 low dose.

    Reporting group title
    NBI-921352 Medium Dose
    Reporting group description
    		 Participants received NBI-921352 medium dose.

    Reporting group title
    NBI-921352 High Dose
    Reporting group description
    		 Participants received NBI-921352 high dose.

    Subject analysis set title
    NBI-921352
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received NBI-921352.

    Primary: Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs

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    End point title
    		 Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs [1]
    End point description
    A TEAE was an adverse event (AE) with an onset date on or after first dose of study drug and within 14 days after the last dose of study drug. An AE was any untoward medical occurrence in a participant administered the study drug that did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required in-patient hospitalization/prolongation of existing hospitalization, was a congenital anomaly, was infection that required treatment parenteral antibiotics, other important medical events which might jeopardize participants, or might require medical/surgical intervention to prevent any of the above. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the ‘Reported Adverse Events’ Section. Safety analysis set: all randomized participants who received at least 1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    From first dose of study drug up to Week 15
    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 endpoint is descriptive in nature.
    End point values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Number of subjects analysed
    26
    25
    25
    25
    Units: participants
        Serious TEAEs
    1
    1
    1
    0
        TEAEs Leading to Study Treatment Discontinuation
    2
    3
    3
    3
        Fatal TEAEs
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Slope Coefficient (β2) of Area Under the Plasma Concentration Versus Time Curve Over a Dosing Interval at Steady State (AUCtau) for Percent Change From Baseline in 28-Day FOS Frequency During the Treatment Period

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    End point title
    		 Slope Coefficient (β2) of Area Under the Plasma Concentration Versus Time Curve Over a Dosing Interval at Steady State (AUCtau) for Percent Change From Baseline in 28-Day FOS Frequency During the Treatment Period [2]
    End point description
    Percent change in 28-day FOS frequency during treatment period compared to baseline period as response variable and steady-state pharmacokinetic (PK) parameter of interest as exposure variable. Exposure was evaluated using AUCtau. Analysis model included 28-day FOS frequency at baseline as a covariate. Results were reported as least-squares (LS) mean estimate of percent change in 28-day FOS frequency for a 1-unit increase in PK parameter (β2 [slope]). The effect size and 95% confidence interval (CI) were obtained for each PK parameter of interest. PK analysis set: participants who received NBI-921352 and had at least 1 reportable plasma concentration value for NBI-921352. ‘Overall number of participants analyzed’ = participants evaluable for this endpoint. As pre-specified, data for this endpoint was collected and reported as a single Arm/Group for any participant who received at least 1 dose of study drug, regardless of their dose level, and who had evaluable data for this endpoint.
    End point type
    Primary
    End point timeframe
    Day 1 (predose) up to Day 77
    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: The statistical analysis was not planned for this endpoint.
    End point values
    		 NBI-921352
    Number of subjects analysed
    70
    Units: ratio
        least squares mean (confidence interval 95%)
    0.00049 (-0.00123 to 0.00220)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Monthly FOS Frequency During the Treatment Period

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    End point title
    		 Percent Change From Baseline in Monthly FOS Frequency During the Treatment Period
    End point description
    Percent change from baseline in 28-day FOS frequency was calculated as: ([frequency during the specified period – frequency during baseline] ÷ frequency during baseline) x 100, where frequency during each period was calculated as: (number of seizures in the period ÷ number of non-missing days in the period) x 28. Non-missing days for seizure diary data were defined as days with >0 seizures documented or confirmation that no seizures occurred on that day. The baseline 28-day FOS frequency was based on seizure data reported in the 56 days immediately preceding randomization. LS mean and standard error (SE) were analyzed using analysis of covariance (ANCOVA). Full analysis set included all randomized participants who received at least 1 dose of study treatment and had at least 1 postbaseline seizure diary entry.
    End point type
    Secondary
    End point timeframe
    From Baseline over the 11-Week treatment period (Day 1 through Day 77)
    End point values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Number of subjects analysed
    26
    25
    25
    25
    Units: percent change
        least squares mean (standard error)
    5.38 ( 9.86 )
    -11.83 ( 10.10 )
    -10.49 ( 10.05 )
    1.28 ( 10.11 )
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Monthly FOS Frequency During the Maintenance Period

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    End point title
    		 Percent Change From Baseline in Monthly FOS Frequency During the Maintenance Period
    End point description
    Percent change from baseline in 28-day FOS frequency was calculated as: ([frequency during the specified period – frequency during baseline] ÷ frequency during baseline) x 100, where frequency during each period was calculated as: (number of seizures in the period ÷ number of non-missing days in the period) x 28. Non-missing days for seizure diary data were defined as days with >0 seizures documented or confirmation that no seizures occurred on that day. The baseline 28-day FOS frequency was based on seizure data reported in the 56 days immediately preceding randomization. The maintenance period was an 8-week period from Day 21 through Day 77. LS mean and SE were analyzed using ANCOVA. Full analysis set included all randomized participants who received at least 1 dose of study treatment and had at least 1 postbaseline seizure diary entry. ‘Overall number of participants analyzed’ = participants evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From Baseline over the 8-Week maintenance period (Day 21 through Day 77)
    End point values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Number of subjects analysed
    26
    23
    25
    25
    Units: percent change
        least squares mean (standard error)
    3.03 ( 10.13 )
    -25.39 ( 10.81 )
    -14.41 ( 10.32 )
    -2.32 ( 10.38 )
    No statistical analyses for this end point

    Secondary: Number of Clinical Global Impression of Change (CGI-C) Responders at Day 77

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    End point title
    		 Number of Clinical Global Impression of Change (CGI-C) Responders at Day 77
    End point description
    The CGI-C is a 7-point scale that required the investigator (or qualified designee) to rate the overall change in the participant’s clinical condition since the initiation of study drug dosing. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants whose CGI-C score was either a 1 (very much improved) or a 2 (much improved) were classified as responders. The number of participants who were classified as responders has been reported. Full analysis set included all randomized participants who received at least 1 dose of study treatment, and had at least 1 postbaseline seizure diary entry.
    End point type
    Secondary
    End point timeframe
    Day 77
    End point values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Number of subjects analysed
    26
    25
    25
    25
    Units: participants
    4
    3
    5
    7
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Response During the Treatment Period

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    End point title
    		 Number of Participants With Treatment Response During the Treatment Period
    End point description
    Treatment response was defined as a participant achieving ≥50% reduction from baseline in 28-day FOS frequency during the treatment period. Full analysis set included all randomized participants who received at least 1 dose of study treatment and had at least 1 postbaseline seizure diary entry.
    End point type
    Secondary
    End point timeframe
    From Baseline over the 11-Week treatment period (Day 1 through Day 77)
    End point values
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Number of subjects analysed
    26
    25
    25
    25
    Units: participants
    2
    3
    3
    5
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to Week 15
    Adverse event reporting additional description
    Safety analysis set included all randomized participants who received at least 1 dose of study treatment. All-Cause Mortality, Serious Adverse Event, and Other Adverse Event data were pre-specified to be collected and reported for throughout the study period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo.

    Reporting group title
    NBI-921352 Low Dose
    Reporting group description
    		 Participants received NBI-921352 low dose.

    Reporting group title
    NBI-921352 Medium Dose
    Reporting group description
    		 Participants received NBI-921352 medium dose.

    Reporting group title
    NBI-921352 High Dose
    Reporting group description
    		 Participants received NBI-921352 high dose.

    Serious adverse events
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure cluster
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo NBI-921352 Low Dose NBI-921352 Medium Dose NBI-921352 High Dose
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 26 (53.85%)
    20 / 25 (80.00%)
    15 / 25 (60.00%)
    18 / 25 (72.00%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    2
    0
    1
    Fall
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 26 (0.00%)
    7 / 25 (28.00%)
    3 / 25 (12.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    9
    3
    6
    Headache
         subjects affected / exposed
    0 / 26 (0.00%)
    6 / 25 (24.00%)
    2 / 25 (8.00%)
    7 / 25 (28.00%)
         occurrences all number
    0
    6
    11
    9
    Seizure
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 25 (8.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    2
    1
    1
    Somnolence
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 25 (12.00%)
    2 / 25 (8.00%)
    3 / 25 (12.00%)
         occurrences all number
    4
    3
    3
    4
    Tremor
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 25 (12.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    3
    0
    2
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    3
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 25 (8.00%)
    3 / 25 (12.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    4
    2
    Fatigue
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 25 (12.00%)
    3 / 25 (12.00%)
    5 / 25 (20.00%)
         occurrences all number
    7
    3
    3
    6
    Gastrointestinal disorders
    Dyspepsia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Nausea
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    2
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 25 (12.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    3
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    1
    1
    5
    Irritability
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 25 (0.00%)
    4 / 25 (16.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    0
    4
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Influenza
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    2
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 25 (4.00%)
    2 / 25 (8.00%)
    2 / 25 (8.00%)
         occurrences all number
    1
    1
    2
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    0
    2
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Nov 2021
    It included following changes: • The study objectives were labeled as primary, secondary, or exploratory and revised to align with the primary, secondary, and exploratory endpoints. • The number of study sites was changed. • Inclusion criteria were revised.
    04 Mar 2022
    It included following changes: • Clarified that direct rollover into an extension study may occur only if a separate active extension study was open for enrollment. • Clarified the requirement for visual field testing before screening. • Reporting and follow-up for pregnancies in female partners of male participants was added.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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