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This Phase 2 open-label, multicenter study will evaluate the safety, tolerability, and efficacy of BMN 190 intracerebroventricular (ICV) administration every other week (qow) for a period of 144 weeks, in patients with CLN2. The study is designed to assess disease progression in CLN2 patients treated with BMN 190 compared to natural history data from untreated historical controls.
BMN 190 is a recombinant form of human tripeptidyl peptidase 1 (TPP1), the enzyme deficient in patients with CLN2 diseases (also known as classical late-infantile CLN2, cLINCL, or Jansky-Bielschowsky disease), a form of Batten Disease. As an enzyme replacement therapy (ERT), BMN 190 is designed to help restore TPP1 enzyme activity. BMN 190 is designed to reduce the progressive, pathologic accumulation of lysosomal storage material. 190-203 is a Phase 2 open-label, multicenter study that will evaluate the safety, tolerability, and efficacy of BMN 190 in pediatric patients < 18 years of age with CLN2 disease. Study drug dosing will be determined by the patient's age and administered via intracerebroventricular (ICV) infusion every other week (qow), for a duration of 144 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) | Experimental | An age-appropriate dose of BMN 190 administered via intracerebroventricular (ICV) infusion every other week (qow) for a duration of 144 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) | Biological |
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| Measure | Description | Time Frame |
|---|---|---|
| Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score. | Rate of decline in 0 to 6-point ML score, & primary analysis was based on up to 3-1 matching of Study 190-901 evaluable participants with Study 190-203 ITT participants. Rate of decline =(-1)x(48x7)x(Ending score - Starting score)/(Ending date - Starting date) A positive rate of decline means that subject declined, a negative rate of decline means that subject improved. The combined motor/gait and language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. The combined ML score is determined as sum of 0-3 point motor(M) & language(L) subscales where 0 represents no function, & 3 represents normal function, & can range from 0(severely impaired) to 6(normal). Thus,high scores describe better function & low scores describe poor function. The starting assessment is baseline ML assessment & ending assessment is last ML score >0. Note for Study 190-901, baseline ML assessment is defined as assessment of matching to Study 190-203 subj. | Baseline to Last assessment (Week 169) |
| Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0 | An unreversed 2-point decline is any decline of 2 points or more that had not reversed to a 1-point decline (or better) at last recorded observation. An unreversed score of 0 is a decline to 0 that had not increased to a score >0 at last recorded observation ML score decline is measured by motor & language domains on CLN2 rating scale. Combined motor/gait &language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. Combined ML score is determined as sum of the 0-3 point motor(M)&language(L) where 0 represents no function, & 3 represents normal function, & can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function & low scores describe poor function Model includes data up to week 169. Estimates from the model are presented for Wks 49, 97 & 145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed 2-point decline/score of 0 at given time points. | Baseline to Last assessment (Week 169) |
| Probability of Decline of Unreversed Motor-language (ML) Score of 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Probability of Decline of Disease Manifestation at Week 49 & 97 | Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores<3, measured atleast 22days apart. Combined motor-language-vision-seizure(MLVS)score as derived from Hamburg CLN2 rating scale, is determined as sum of 0-3 point motor(M)language(L)visio(V)&seizure(S) subscales where 0 represents no function,&3 represents normal function,&can range from 0(severely impaired)to12(normal).Thus, high scores describe better function & low scores describe poor function. 901 subj weighted according to no.of matches:weights for 3,2,&1 study 901 subj matched to a given study 203 subj are 1/3,1/2, &1 times N901/N203 respectively. N901 is no.of 901 subj matched to 203 subj(ie.18)&N203 is no.203 subj who had matches (i.e.7).203 subj who had matches were assigned weight of 1. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time points |
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Enrollment is complete.
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director, MD | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States | ||
| Universitaetsklinikum Hamburg-Eppendorf |
A total of 14 participants were enrolled and treated in study 190-203. 13 participants completed the study, and 1 participant withdrew to receive treatment commercially.
The 190-203 study required enrollment of at least 10 participants, including at least 5 participants with a combined ML score >= 5 points (mild or pre-symptomatic disease), at least 5 participants with a ML score < 5points (moderate disease), and at least 5 participants < 2 years of age.
Study 190-203 was conducted at 4 clinic sites:One each in Germany, Italy, the United Kingdom and the United States.
The comparator group for determination of the primary efficacy outcome measures in this study was comprised of 29 Natural History (NH) subjects with late-infantile neuronal ceroid lipofuscinosis disease, also known as classical late-infantile CLN2, cLINCL, or Jansky-Bielschowsky disease, a form of Batten Disease (CLN2) disease selected from the DEM-CHILD database (NCT04613089).
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| ID | Title | Description |
|---|---|---|
| FG000 | BMN 190-203 | BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to < 6 months: 100 mg, 6 months to < 1 year: 150 mg, 1 year to < 2 years: 200 mg (first four doses), 300 mg (subsequent doses) >=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 5, 2019 | Jun 14, 2024 |
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| Intracerebroventricular access device | Device | Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug. |
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The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function.
Model includes data up to week 169. Estimates from the model are presented for Weeks 49, 97 and 145.
No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed decline/score of 0 at given time points
| Baseline to Last assessment (Week 169) |
| Rate of Decline in Individual Motor Domains | Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point motor (M) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function, and low scores describe poor function. | Baseline to Last assessment (Week 169) |
| Rate of Decline in Individual Language Domains | Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point language (L) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function and low scores describe poor function. Patients with baseline score of 0 are excluded. | Baseline to Last assessment (Week 169) |
| Baseline to Last assessment (Week 169) |
| Probability of Decline of Disease Manifestation at Week 145 | Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores<3,measured atleast 22days apart Combined MLVS score,as derived from Hamburg CLN2 rating scale,is determined as sum of 0-3 point motor(M)language(L)vision(V)&seizure(S) subscales where 0 represents no function,&3 represents normal function,&can range from 0(severely impaired) to 12(normal).Thus,high scores describe better function&low scores describe poor function 901 subj weighted according to no.of matches:weights for 3,2,&1 study 901 subj matched to given study 203 subj are 1/3,1/2, &1 times N901/N203 respectively.N901 is no.of 901 subj matched to 203 subj(ie.18)&N203 is no.203 subj who had matches(i.e.7).203 subj who had matches were assigned weight of 1 Model includes data upto wk169.Estimates from model are presented for Wk145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time point | Baseline to Week 145 |
| Change From Baseline in ML Scale Score | The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | Baseline to Week 49, Week 97, Week 145, & Week 169 |
| Changes From Baseline in MLV Scale Score | The combined motor-language-vision (MLV) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M), language (L) & vision (V) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 9 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | Baseline to Week 49, Week 97, Week 145, & Week 169 |
| Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. | The combined motor-language-vision-seizure (MLVS) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M) and language (L) vision (V) and seizure (S) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 12 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | Baseline to Week 49, Week 97, Week 145, & Week 169 |
| Percentage Change From Baseline to Last Assessment: Volume of Cerebrospinal Fluid (mL) | Baseline to Last assessment (Week 169) |
| Percentage Change From Baseline to Last Assessment: Volume of Total Cortical Gray Matter (mL) | Baseline to Last assessment (Week 169) |
| Percentage Change From Baseline to Last Assessment: Volume of Total White Matter (mL) | Baseline to Last assessment (Week 169) |
| Change From Baseline to Last Assessment: Whole Brain Apparent Diffusion Coefficient Value | The apparent diffusion coefficient (ADC) represents the calculated diffusion coefficient of water molecules in the direction of the applied gradients measured during diffusion MRI, a technique used to explore the architecture and microstructural properties of both the white and gray matter of the brain. | Baseline to Last assessment (Week 169) |
| Hamburg |
| 20246 |
| Germany |
| Children's Hospital Bambino Gesù,IRCCS | Rome | Piazza | 00165 | Italy |
| Great Ormond Street Childrens Hospital | London | WC1N 3JH | United Kingdom |
| FG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| COMPLETED |
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| NOT COMPLETED |
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The 901 subjects weighted according to number of matches: weights for 3, 2, and 1 study 901 subject matched to a given study 203 subject are 1/3,1/2, and 1 times N901/N203 respectively. N901 is the number of 901 subjects matched to 203 subjects (i.e. 29) and N203 is the number of 203 subjects who had matches (i.e. 12). The 203 subjects who had matches were assigned the weight of 1. The common alleles are c.509-1G and c.622C>T
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| ID | Title | Description |
|---|---|---|
| BG000 | BMN 190-203 | BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to < 6 months: 100 mg, 6 months to < 1 year: 150 mg, 1 year to < 2 years: 200 mg (first four doses), 300 mg (subsequent doses) >=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug. |
| BG001 | Natural History Comparator:190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The 901 subjects weighted according to number of matches: weights for 3, 2, and 1 study 901 subject matched to a given study 203 subject are 1/3,1/2, and 1 times N901/N203 respectively. N901 is the number of 901 subjects matched to 203 subjects (i.e. 29) and N203 is the number of 203 subjects who had matches (i.e. 12). The 203 subjects who had matches were assigned the weight of 1. The common alleles are c.509-1G and c.622C>T | Mean | Standard Deviation | years |
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| Sex/Gender, Customized | Percentages were calculated using total no. subjects in ITT Population & in matched subjects as denominators separately Number of subjects for Natural history study was rounded to nearest whole no. The 901 subjects weighted according to no. of matches: weights for 3, 2,&1 study 901 subject matched to a given study 203 subject are 1/3,1/2, & 1 times N901/N203 respectively. N901 is number of 901 subjects matched to 203 subjects (i.e. 29) & N203 is number of 203 subjects who had matches (i.e. 12). 203 subjects who had matches were assigned weight of 1. Common alleles are c.509-1G & c.622C>T | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | The 901 subjects weighted according to number of matches: weights for 3, 2, and 1 study 901 subject matched to a given study 203 subject are 1/3,1/2, and 1 times N901/N203 respectively. N901 is the number of 901 subjects matched to 203 subjects (i.e. 29) and N203 is the number of 203 subjects who had matches (i.e. 12). The 203 subjects who had matches were assigned the weight of 1. The common alleles are c.509-1G and c.622C>T | Count of Participants | Participants |
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| Race/Ethnicity, Customized | The 901 subjects weighted according to number of matches: weights for 3, 2, and 1 study 901 subject matched to a given study 203 subject are 1/3,1/2, and 1 times N901/N203 respectively. N901 is the number of 901 subjects matched to 203 subjects (i.e. 29) and N203 is the number of 203 subjects who had matches (i.e. 12). The 203 subjects who had matches were assigned the weight of 1. The common alleles are c.509-1G and c.622C>T | Count of Participants | Participants |
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| CLN2 motor-language (ML) score | The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function & low scores describe poor function | Mean | Standard Deviation | score on a scale |
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| CLN2 motor scale score at Baseline | The 901 subjects weighted according to No.of matches:weights for 3,2,&1 study 901 subject matched to a given study 203 subject are 1/3,1/2,&1 times N901/N203 respectively. N901 is No. of 901 subjects matched to 203 subjects(ie 29)& N203 is No.of 203 subjects who had matches(ie12)203 subjects who had matches were assigned weight of 1. Common alleles are c.509-1G & c.622C>T The 0-3 point motor(M) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function,& 3 represents normal function.Thus,high scores describe better function & low scores describe poor function | Mean | Standard Deviation | score on a scale |
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| CLN2 language scale score at Baseline | The 901 subjects weighted according to No.of matches:weights for 3,2,&1 study 901 subject matched to a given study 203 subject are 1/3,1/2,&1 times N901/N203 respectively.N901 is No.of 901 subjects matched to 203 subjects(ie 29)& N203 is No.of 203 subjects who had matches(ie12). 203 subjects who had matches were assigned weight of 1. Common alleles are c.509-1G & c.622C>T 0-3 point language (L) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, & 3 represents normal function.Thus, high scores describe better function & low scores describe poor function | Mean | Standard Deviation | Score on a scale |
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| CLN2 motor-language-vision-seizure (MLVS) score | The combined motor-language-vision-seizure (MLVS) score as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M) and language (L) vision (V) and seizure (S) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 12 (normal). Thus, high scores describe better function & low scores describe poor function. | One subject in the natural history group had missing baseline values for the vision and seizure domains. Therefore MLVS score could not be calculated. | Mean | Standard Deviation | Score on a scale |
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| Age at disease onset (years) | The 901 subjects weighted according to number of matches: weights for 3, 2, and 1 study 901 subject matched to a given study 203 subject are 1/3,1/2, and 1 times N901/N203 respectively. N901 is the number of 901 subjects matched to 203 subjects (i.e. 29) and N203 is the number of 203 subjects who had matches (i.e. 12). The 203 subjects who had matches were assigned the weight of 1. The common alleles are c.509-1G and c.622C>T | Age at disease onset was missing for several subjects in both 190-203 and the natural history comparator. | Mean | Standard Deviation | years |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score. | Rate of decline in 0 to 6-point ML score, & primary analysis was based on up to 3-1 matching of Study 190-901 evaluable participants with Study 190-203 ITT participants. Rate of decline =(-1)x(48x7)x(Ending score - Starting score)/(Ending date - Starting date) A positive rate of decline means that subject declined, a negative rate of decline means that subject improved. The combined motor/gait and language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. The combined ML score is determined as sum of 0-3 point motor(M) & language(L) subscales where 0 represents no function, & 3 represents normal function, & can range from 0(severely impaired) to 6(normal). Thus,high scores describe better function & low scores describe poor function. The starting assessment is baseline ML assessment & ending assessment is last ML score >0. Note for Study 190-901, baseline ML assessment is defined as assessment of matching to Study 190-203 subj. | Matched ITT BMN 190-203: Two subjects in 190-203 ITT population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: • Equal ML score • Age within 3 months • Genome: equal number of common alleles (c.622C→T, c.509.1G→C) Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description. | Posted | Mean | Standard Deviation | change in score/48 wk | Baseline to Last assessment (Week 169) |
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| Primary | Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0 | An unreversed 2-point decline is any decline of 2 points or more that had not reversed to a 1-point decline (or better) at last recorded observation. An unreversed score of 0 is a decline to 0 that had not increased to a score >0 at last recorded observation ML score decline is measured by motor & language domains on CLN2 rating scale. Combined motor/gait &language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. Combined ML score is determined as sum of the 0-3 point motor(M)&language(L) where 0 represents no function, & 3 represents normal function, & can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function & low scores describe poor function Model includes data up to week 169. Estimates from the model are presented for Wks 49, 97 & 145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed 2-point decline/score of 0 at given time points. | Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population(N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles(c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description. | Posted | Number | 95% Confidence Interval | Probability of decline | Baseline to Last assessment (Week 169) |
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| Primary | Probability of Decline of Unreversed Motor-language (ML) Score of 0 | The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Model includes data up to week 169. Estimates from the model are presented for Weeks 49, 97 and 145. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed decline/score of 0 at given time points | Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description | Posted | Number | 95% Confidence Interval | Probability of decline | Baseline to Last assessment (Week 169) |
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| Primary | Rate of Decline in Individual Motor Domains | Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point motor (M) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function, and low scores describe poor function. | Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description. | Posted | Mean | Standard Deviation | change in score/48 wk | Baseline to Last assessment (Week 169) |
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| Primary | Rate of Decline in Individual Language Domains | Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point language (L) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function and low scores describe poor function. Patients with baseline score of 0 are excluded. | Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description. | Posted | Mean | Standard Deviation | change in score/48 wk | Baseline to Last assessment (Week 169) |
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| Secondary | Probability of Decline of Disease Manifestation at Week 49 & 97 | Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores<3, measured atleast 22days apart. Combined motor-language-vision-seizure(MLVS)score as derived from Hamburg CLN2 rating scale, is determined as sum of 0-3 point motor(M)language(L)visio(V)&seizure(S) subscales where 0 represents no function,&3 represents normal function,&can range from 0(severely impaired)to12(normal).Thus, high scores describe better function & low scores describe poor function. 901 subj weighted according to no.of matches:weights for 3,2,&1 study 901 subj matched to a given study 203 subj are 1/3,1/2, &1 times N901/N203 respectively. N901 is no.of 901 subj matched to 203 subj(ie.18)&N203 is no.203 subj who had matches (i.e.7).203 subj who had matches were assigned weight of 1. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time points | Matched ITT BMN190-203:2 subj in190-203 ITT Population(N=14)were excluded from 190-203 ITT analysis with matching(N=12)who did not match with any190-901 subj on matching criteria.Matching criteria at baseline were:Equal ML score,age<3 months&genome with equal no.of common alleles(c.622C→T,c.509.1G→C). Matched190-901 Natural history population:29 subj from DEM-CHILD database satisfying criteria listed in Arm descp Model includes data upto wk169.Estimates from model are presented for Wks 49&97 | Posted | Number | 95% Confidence Interval | Probability of decline | Baseline to Last assessment (Week 169) |
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| Secondary | Probability of Decline of Disease Manifestation at Week 145 | Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores<3,measured atleast 22days apart Combined MLVS score,as derived from Hamburg CLN2 rating scale,is determined as sum of 0-3 point motor(M)language(L)vision(V)&seizure(S) subscales where 0 represents no function,&3 represents normal function,&can range from 0(severely impaired) to 12(normal).Thus,high scores describe better function&low scores describe poor function 901 subj weighted according to no.of matches:weights for 3,2,&1 study 901 subj matched to given study 203 subj are 1/3,1/2, &1 times N901/N203 respectively.N901 is no.of 901 subj matched to 203 subj(ie.18)&N203 is no.203 subj who had matches(i.e.7).203 subj who had matches were assigned weight of 1 Model includes data upto wk169.Estimates from model are presented for Wk145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time point | Matched ITT BMN190-203:2 subj in 190-203 ITT Pop(N=14) were excluded from 190-203 ITT analysis with matching(N=12) who did not match with any 190-901 subj on matching criteria. Matching criteria at baseline were:Equal ML score, age within 3 months & genome with equal no. of common alleles(c.622C→T, c.509.1G→C). Matched 190-901 Natural history pop:29 subj from DEM-CHILD database satisfying criteria listed in Arm/Group descp. No.of subj analyzed for 190-901=0 & hence this arm is not included | Posted | Number | 95% Confidence Interval | Probability of decline | Baseline to Week 145 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in ML Scale Score | The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | 190-901 participants weighted according to no. of matches: weights for 3,2,&1 study 190-901 participant matched to a given Study190-203 participant were1/3,1/2,&1 times N901/N203, respectively. N901 was no. of 190-901 participants matched to 190-203 participants (ie,29) &N203 was no. of 190-203 participants who had matches (ie,12).190-203 participants who had matches were assigned weight of 1. Each participant in Study 190-901 had their scores imputed to time points using linear interpolation | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 49, Week 97, Week 145, & Week 169 |
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| Secondary | Changes From Baseline in MLV Scale Score | The combined motor-language-vision (MLV) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M), language (L) & vision (V) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 9 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | 190-901 participants weighted according to no. of matches: weights for 3,2,&1 study 190-901 participant matched to a given Study190-203 participant were1/3,1/2,&1 times N901/N203, respectively. N901 was no. of 190-901 participants matched to 190-203 participants (ie,29) &N203 was no. of 190-203 participants who had matches (ie,12).190-203 participants who had matches were assigned weight of 1. Each participant in Study 190-901 had their scores imputed to time points using linear interpolation | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 49, Week 97, Week 145, & Week 169 |
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| Secondary | Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. | The combined motor-language-vision-seizure (MLVS) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M) and language (L) vision (V) and seizure (S) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 12 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points. | 190-901 participants weighted according to no. of matches: weights for 3,2,&1 study 190-901 participant matched to a given Study190-203 participant were1/3,1/2,&1 times N901/N203, respectively. N901 was no. of 190-901 participants matched to 190-203 participants (ie,29) &N203 was no. of 190-203 participants who had matches (ie,12).190-203 participants who had matches were assigned weight of 1. Each participant in Study 190-901 had their scores imputed to time points using linear interpolation | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 49, Week 97, Week 145, & Week 169 |
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| Secondary | Percentage Change From Baseline to Last Assessment: Volume of Cerebrospinal Fluid (mL) | Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available. | Posted | Mean | Standard Deviation | Percentage | Baseline to Last assessment (Week 169) |
|
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| Secondary | Percentage Change From Baseline to Last Assessment: Volume of Total Cortical Gray Matter (mL) | Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available. | Posted | Mean | Standard Deviation | Percentage | Baseline to Last assessment (Week 169) |
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| Secondary | Percentage Change From Baseline to Last Assessment: Volume of Total White Matter (mL) | Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available. | Posted | Mean | Standard Deviation | Percentage | Baseline to Last assessment (Week 169) |
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| Secondary | Change From Baseline to Last Assessment: Whole Brain Apparent Diffusion Coefficient Value | The apparent diffusion coefficient (ADC) represents the calculated diffusion coefficient of water molecules in the direction of the applied gradients measured during diffusion MRI, a technique used to explore the architecture and microstructural properties of both the white and gray matter of the brain. | Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available. | Posted | Mean | Standard Deviation | mm^2/s | Baseline to Last assessment (Week 169) |
|
|
Up-to Safety Follow-Up (6 months after last dose).
Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR)
AEs&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BMN 190 Recombinant Human Tripeptidyl Peptidase-1 (rhTPP1) | BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to < 6 months: 100 mg, 6 months to < 1 year: 150 mg, 1 year to < 2 years: 200 mg (first four doses), 300 mg (subsequent doses) >=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug. | 0 | 14 | 12 | 14 | 14 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deafness unilateral | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Mycoplasma infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrointestinal fistula | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Adenoidal hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Complication of device insertion | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Medical device site haematoma | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Medical device site irritation | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pleocytosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Propionibacterium test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Device leakage | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Extensor plantar response | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Medication monitoring error | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Atonic seizures | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Device leakage | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Speech disorder developmental | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Adenoidal hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyskinesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Foreign body | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Needle issue | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Parainfluenzae virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Viral test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Athetosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Atrioventricular block second degree | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Attention deficit/hyperactivity disorder | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bicuspid aortic valve | Congenital, familial and genetic disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| CSF red blood cell count positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Complication of device insertion | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Deafness unilateral | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Device breakage | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device malfunction | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ear haemorrhage | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Electroencephalogram abnormal | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Exanthema subitum | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Eye movement disorder | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Eyelid contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Febrile convulsion | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrointestinal fistula | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Human rhinovirus test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Language disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Medical device site haematoma | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Medical device site irritation | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Medical device site swelling | General disorders | MedDRA | Systematic Assessment |
| |
| Mycoplasma infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Myoclonic epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Otitis externa | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Partial seizures with secondary generalisation | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Periorbital haemorrhage | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Petit mal epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngotonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pleocytosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia chlamydial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Propionibacterium test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyuria | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory syncytial virus test | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respirovirus test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rotavirus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure cluster | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Talipes | Congenital, familial and genetic disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
The only disclosure restrictions on the PI are that (i) they cannot publish results communications until after the multicenter dataset is published, (ii) the sponsor has an opportunity to review results communications prior to public release, and (iii) the sponsor can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pascal Reisewitz, Global Medical Director, PhD | BioMarin Pharmaceutical Inc | 1-800-983-4587 | medinfo@bmrn.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 18, 2022 | Apr 23, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009472 | Neuronal Ceroid-Lipofuscinoses |
| ID | Term |
|---|---|
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000621431 | cerliponase alfa |
Not provided
Not provided
Not provided
|
| Male |
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| Unknown or Not Reported |
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BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to < 6 months: 100 mg, 6 months to < 1 year: 150 mg, 1 year to < 2 years: 200 mg (first four doses), 300 mg (subsequent doses) >=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study.
BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)
Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.
| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| OG001 | Natural History Comparator: 190-901 Participants | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have:
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| Participants |
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