Cerebral Palsy, Chronic Troublesome Sialorrhea, Intellectual Disability, Stroke, Traumatic Brain Injury
Conditions
Brief summary
The objective of this study is to investigate the efficacy and safety of NT 201 compared with placebo for the treatment of chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents naïve to Botulinum neurotoxin treatment and aged 2-17 years.
Interventions
DRUGNT 201 Placebo
NT 201 placebo matching injection.
DRUGNT 201
NT 201 injection.
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female child/adolescent age 2-17 years. * Any neurological disorder (e.g. cerebral palsy or traumatic brain injury) and/or intellectual disability associated with chronic troublesome sialorrhea for at least 3 months up to the screening. In subjects with intellectual disability (ID) without neurological disorders, a diagnosis of ID by a specialist, e.g. pediatrician or by a center for developmental medicine is required for inclusion. * Severe drooling (modified Teacher´s Drooling Scale \[mTDS\] ≥ 6; clothing occasionally becomes damp) as rated by the investigator. * Parental consent and the subject's oral or written assent as the subject is able to provide.
Exclusion criteria
* Chronic troublesome sialorrhea not related to neurological disorders and/or intellectual disability. * Body weight \< 12 kg. * Pharmacological treatment for sialorrhea or concomitant medication known to influence sialorrhea strongly (e.g. anticholinergics with exception of locally applied or short acting drugs used under general anesthesia) within 45 days before baseline and during the entire study period. * Any previous known or suspected hypersensitivity to Botulinum toxin. * Aspiration pneumonia within 6 month before screening. * Any previous treatment with Botulinum toxin for any body region during the year before screening or within the screening period * Prior, concomitant or planned surgery or irradiation to head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within one year before screening or planned for any part of the entire study period. * Concurrent diseases, including hematological, hepatic, renal, gastrointestinal, endocrine, pulmonary, musculoskeletal, or psychiatric diseases or conditions, which in the judgment of the investigator would put the subject at risk while in the study, could influence the results of the study, or negatively impact the subject's ability to participate in the study. * Extremely poor dental and/or oral condition that might preclude safe study participation by the judgment of the investigator. * Nursing mother or pregnant female subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4 | Baseline and Week 4 | This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea. |
| Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s) | Week 4 | This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). |
| Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Baseline up to Week 64 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Baseline up to Week 64 | — |
| Change From Baseline in uSFR at Weeks 8 and 12 | Baseline and Weeks 8 and 12 | This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea. |
| Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Baseline up to Week 64 | — |
| Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Baseline up to Week 64 | — |
| GICS at Weeks 8 and 12 | Weeks 8 and 12 | This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). |
| Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Baseline up to Week 64 | — |
Countries
Georgia, Hungary, Poland, Russia, Serbia, Ukraine
Participant flow
Recruitment details
The study was conducted at 28 investigational sites in Georgia, Hungary, Poland, Russia, Serbia, and Ukraine.
Pre-assignment details
A total of 281 participants were screened, out of which 256 participants were enrolled/randomized into the study. Of these 256 participants, 255 participants received the study treatment. A total of 247 participants who completed the Main Period (MP) entered the Open-label Extension Period (OLEX) of the study.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm. | 72 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. | 148 |
| Open-label, MP: NT 201 (Age 2 to 5 Years) Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. | 35 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Main Period (MP) (up to 16 Weeks) | Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Main Period (MP) (up to 16 Weeks) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Main Period (MP) (up to 16 Weeks) | Randomized, not Treated | 0 | 0 | 1 | 0 | 0 |
| Main Period (MP) (up to 16 Weeks) | Withdrawal by Subject | 2 | 0 | 1 | 0 | 0 |
| OLEX Period (up to 48 Weeks) | Adverse Event | 0 | 0 | 0 | 4 | 0 |
| OLEX Period (up to 48 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 2 | 0 |
| OLEX Period (up to 48 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 |
| OLEX Period (up to 48 Weeks) | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| OLEX Period (up to 48 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 16 | 0 |
Baseline characteristics
| Characteristic | Total | Double-blind MP: Placebo (Age 6 to 17 Years) | Double-blind, MP: NT 201 (Age 6 to 17 Years) | Open-label, MP: NT 201 (Age 2 to 5 Years) |
|---|---|---|---|---|
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 76 Participants | 24 Participants | 52 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 179 Participants | 48 Participants | 96 Participants | 35 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Body Mass Index (BMI) | 15.9 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.23 | 16.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.65 | 15.8 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.25 | 15.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.85 |
| Height | 129.1 centimeter (cm) STANDARD_DEVIATION 19.64 | 135.3 centimeter (cm) STANDARD_DEVIATION 16.92 | 132.8 centimeter (cm) STANDARD_DEVIATION 17.15 | 101.1 centimeter (cm) STANDARD_DEVIATION 8.09 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 255 Participants | 72 Participants | 148 Participants | 35 Participants |
| Sex: Female, Male Female | 95 Participants | 27 Participants | 55 Participants | 13 Participants |
| Sex: Female, Male Male | 160 Participants | 45 Participants | 93 Participants | 22 Participants |
| Weight | 27.6 kilogram (kg) STANDARD_DEVIATION 11.78 | 30.8 kilogram (kg) STANDARD_DEVIATION 11.67 | 28.8 kilogram (kg) STANDARD_DEVIATION 11.48 | 15.7 kilogram (kg) STANDARD_DEVIATION 3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 148 | 0 / 35 | 0 / 214 | 0 / 33 |
| other Total, other adverse events | 3 / 72 | 3 / 148 | 2 / 35 | 34 / 214 | 12 / 33 |
| serious Total, serious adverse events | 1 / 72 | 0 / 148 | 1 / 35 | 8 / 214 | 0 / 33 |
Outcome results
Primary
Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4
This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.
Time frame: Baseline and Week 4
Population: The full analysis set (FAS) is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4 | -0.07 gram per minute (g/min) | Standard Error 0.015 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4 | -0.14 gram per minute (g/min) | Standard Error 0.012 |
Comparison: Least square mean (LS-Mean) is from a mixed model repeated measurement (MMRM) analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.p-value: =0.001295% CI: [-0.1, -0.03]MMRM
Primary
Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)
This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
Time frame: Week 4
Population: The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s) | 0.63 units on a scale | Standard Error 0.104 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s) | 0.91 units on a scale | Standard Error 0.075 |
Comparison: LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline Modified Teacher Drooling Scale (mTDS) score as covariate.p-value: =0.03295% CI: [0.02, 0.53]MMRM
Primary
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
Time frame: Baseline up to Week 64
Population: SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. n is number of participants evaluable for this measure at a given time period and who were included in the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | First injection cycle (MP) | 11 Participants |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall | 11 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | First injection cycle (MP) | 27 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall | 27 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | First injection cycle (MP) | 5 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall | 5 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Third injection cycle (OLEX) | 35 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Second injection cycle (OLEX) | 44 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Fourth injection cycle (OLEX) | 40 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall | 92 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Fourth injection cycle (OLEX) | 11 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Second injection cycle (OLEX) | 7 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Third injection cycle (OLEX) | 5 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall | 15 Participants |
Secondary
Change From Baseline in uSFR at Weeks 8 and 12
This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.
Time frame: Baseline and Weeks 8 and 12
Population: The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Change From Baseline in uSFR at Weeks 8 and 12 | Change at Week 8 | -0.07 g/min | Standard Error 0.015 |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Change From Baseline in uSFR at Weeks 8 and 12 | Change at Week 12 | -0.06 g/min | Standard Error 0.016 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Change From Baseline in uSFR at Weeks 8 and 12 | Change at Week 8 | -0.16 g/min | Standard Error 0.012 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Change From Baseline in uSFR at Weeks 8 and 12 | Change at Week 12 | -0.16 g/min | Standard Error 0.013 |
Comparison: Statistical analysis at Week 8: LS-Mean is from a MMRM analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.p-value: <0.000195% CI: [-0.12, -0.05]MMRM
Comparison: Statistical analysis at Week 12: LS-Mean is from a MMRM analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.p-value: <0.000195% CI: [-0.14, -0.06]MMRM
Secondary
GICS at Weeks 8 and 12
This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
Time frame: Weeks 8 and 12
Population: The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | GICS at Weeks 8 and 12 | Week 12 | 0.47 units on a scale | Standard Error 0.111 |
| Double-blind MP: Placebo (Age 6 to 17 Years) | GICS at Weeks 8 and 12 | Week 8 | 0.54 units on a scale | Standard Error 0.096 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | GICS at Weeks 8 and 12 | Week 12 | 0.87 units on a scale | Standard Error 0.073 |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | GICS at Weeks 8 and 12 | Week 8 | 0.94 units on a scale | Standard Error 0.068 |
Comparison: Statistical analysis at Week 8: LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline mTDS score as covariate.p-value: =0.000895% CI: [0.17, 0.63]MMRM
Comparison: Statistical analysis at Week 12: LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit\*treatment as interaction term, visit as repeated factor, and baseline mTDS score as covariate.p-value: =0.002695% CI: [0.14, 0.66]MMRM
Secondary
Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle
Time frame: Baseline up to Week 64
Population: SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. n is number of participants evaluable for this measure at a given time period and who were included in the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Overall | 1 Participants |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Overall | 1 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Overall | 1 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Second injection cycle (OLEX) | 2 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Overall | 4 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Third injection cycle (OLEX) | 2 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Overall | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Third injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle | Second injection cycle (OLEX) | 0 Participants |
Secondary
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle
Time frame: Baseline up to Week 64
Population: SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. n is number of participants evaluable for this measure at a given time period and who were included in the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | First injection cycle (MP) | 0 Participants |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Overall | 0 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | First injection cycle (MP) | 2 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Overall | 2 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Overall | 1 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Overall | 10 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Second injection cycle (OLEX) | 5 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Third injection cycle (OLEX) | 5 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 1 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Second injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Third injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle | Overall | 0 Participants |
Secondary
Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle
Time frame: Baseline up to Week 64
Population: SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. n is number of participants evaluable for this measure at a given time period and who were included in the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | First injection cycle (MP) | 0 Participants |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Overall | 0 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Overall | 1 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | First injection cycle (MP) | 0 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Overall | 0 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Third injection cycle (OLEX) | 1 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Second injection cycle (OLEX) | 3 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Overall | 4 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Second injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Third injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle | Overall | 0 Participants |
Secondary
Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle
Time frame: Baseline up to Week 64
Population: SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. n is number of participants evaluable for this measure at a given time period and who were included in the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| Double-blind MP: Placebo (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Overall | 1 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | First injection cycle (MP) | 0 Participants |
| Double-blind, MP: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Overall | 0 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | First injection cycle (MP) | 1 Participants |
| Open-label, MP: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Overall | 1 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Third injection cycle (OLEX) | 5 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Second injection cycle (OLEX) | 3 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 6 to 17 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Overall | 8 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Fourth injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Second injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Third injection cycle (OLEX) | 0 Participants |
| OLEX: NT 201 (Age 2 to 5 Years) | Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle | Overall | 0 Participants |