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The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.
BMN 190 is a recombinant form of human tripeptidyl peptidase 1 (TPP1), the enzyme deficient in patients with CLN2 disease (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. The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1) | Experimental | All 190-202 study subjects administered BMN 190 300 mg by continuous Intracerebroventricular (ICV) infusion at a rate of 2.5 mL/hour for approximately 4 hours) every 14 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMN 190 | Biological | 300 mg Intracerebroventricular (ICV) infusion administered every other week for up to 240 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Probability of Unreversed 2-point Decline in Motor-language (ML) Score or Score of 0 | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function. In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (i.e., baseline ML score and age as continuous covariates, and genotype [common alleles] and sex as categorical covariates). | Up to Week 289 |
| Probability of Unreversed Motor-language (ML) Score of Zero. | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function. In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (baseline ML score, age, genotype [common alleles], and sex). | Up to Week 289 |
| Measure | Description | Time Frame |
|---|---|---|
| Whole Brain Volume | Percentage change from Baseline to Last Observation: Whole Brain volume | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
| Volume of Cerebrospinal Fluid | Percentage Change from Baseline to last observation: Volume of cerebrospinal fluid |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor, MD | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States | ||
| Universitaetsklinikum Hamburg-Eppendorf |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38776275 | Derived | Specchio N, Gissen P, de Los Reyes E, Olaye A, Camp C, Curteis T, Griffiths A, Butt T, Cohen-Pfeffer J, Slasor P, Sisic Z, Jain M, Schulz A. Exploring concurrent validity of the CLN2 Clinical Rating Scale: Comparison to PedsQL using cerliponase alfa clinical trial data. PLoS One. 2024 May 22;19(5):e0302382. doi: 10.1371/journal.pone.0302382. eCollection 2024. | |
| 38101904 |
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190-202 is the extension of treatment & follow-up for subjects enrolled in Study 190-201. The ITT analysis population was comprised of the 23 subjects who completed the 190-201 study and enrolled in the 190-202 study (completed 48 weeks in 190-201, met all other 190-202 study inclusion criteria and to whom none of the 190-202 study exclusion criteria applied). The safety analysis population in Study 190-202 was comprised of the 24 subjects in Study 190-201 who had an ICV access device implanted.
190-201 was conducted at 5 clinic sites in Germany, Italy, the United Kingdom and the United States. One subject from one of the two 190-201 sites in the United Kingdom withdrew after 1 dose of BMN 190 and therefore this site was not activated in 190-202.
The comparator group for determination of the primary efficacy outcome measures in this study was comprised of 42 Natural History (NH) subjects with CLN2 disease selected from the DEM-CHILD database (NCT04613089).
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| ID | Title | Description |
|---|---|---|
| FG000 | 190-202 (300 mg) | 190-202 Intent to Treat (ITT)/Efficacy Population (n = 23): The 23 subjects who completed the 190-201 study and enrolled in the 190-202 study (i.e., completed 48 weeks in Study 190-201, met all other 190-202 study inclusion criteria and to whom none of the 190-202 study exclusion criteria applied). 190-202 Safety Population (n = 24): All study subjects who had an ICV access device implanted in Study 190-201. |
| 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 | Dec 17, 2018 | Dec 9, 2021 |
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Because of practical (limited number of available patients) and ethical (neurosurgery in children with fatal neurologic disease) concerns, this study design could not involve contemporaneous, matched, randomized, blinded, or untreated control subjects. As such, data from the DEM-CHILD Multi-Center Clinical NCL Database at the University Medical Center in Hamburg, Germany (NCT04613089) was used as a control group (i.e., Natural History [NH] comparator) to determine the primary efficacy outcome measures for this study. The NH comparator was comprised of subjects from the DEM-CHILD database who satisfied the 190-201 inclusion criterion: Age ≥ 3, and at least one ML score ≥ 3 at age ≥ 3 years and further, who had at least two CLN2 assessments with values within the range 1 - 5 and at least 6 months apart.
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|
| Intracerebroventricular (ICV) 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. |
|
| Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
| Volume of Total Cortical Gray Matter | Percentage Change from Baseline to last observation: Volume of total cortical gray matter | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
| Total White Matter Volume | Percentage Change from Baseline to last observation: Total white matter volume | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
| Whole Brain Apparent Diffusion Coefficient | Change from Baseline to last observation Whole brain apparent diffusion coefficient | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
| Hamburg |
| 20246 |
| Germany |
| Children's Hospital Bambino Gesù,IRCCS | Rome | Piazza | 00165 | Italy |
| Great Ormond Street Childrens Hospital | London | WC1N 3JH | United Kingdom |
| Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J. Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study. Lancet Neurol. 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. |
| 33980287 | Derived | Gissen P, Specchio N, Olaye A, Jain M, Butt T, Ghosh W, Ruban-Fell B, Griffiths A, Camp C, Sisic Z, Schwering C, Wibbeler E, Trivisano M, Lee L, Nickel M, Mortensen A, Schulz A. Investigating health-related quality of life in rare diseases: a case study in utility value determination for patients with CLN2 disease (neuronal ceroid lipofuscinosis type 2). Orphanet J Rare Dis. 2021 May 12;16(1):217. doi: 10.1186/s13023-021-01829-x. |
| 29688815 | Derived | Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschutter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24. |
| FG001 | Natural History Comparator | The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-201 inclusion criterion: Age ≥ 3 years; and at least one ML score ≥3 points at age ≥3 years and further, who had at least two CLN2 assessments with values within the range 1 to 5 points and at least 6 months apart. |
| COMPLETED |
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| NOT COMPLETED |
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The demographic characteristics of the enrolled population are summarized for the 190-201/202 study (24 subjects). The demographic characteristics of the control group (NH comparator) which were necessary to determine the primary efficacy outcome measures, are also included (42 subjects).
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| ID | Title | Description |
|---|---|---|
| BG000 | 190-202 (300 mg) | 190-202 Intent to Treat (ITT)/Efficacy Population (n = 23): The 23 subjects who completed the 190-201 study and enrolled in the 190-202 study (i.e., completed 48 weeks in Study 190-201, met all other 190-202 study inclusion criteria and to whom none of the 190-202 study exclusion criteria applied). 190-202 Safety Population (n = 24): All study subjects who had an ICV access device implanted in Study 190-201. |
| BG001 | Natural History Comparator | Because of practical (limited number of available patients) and ethical (neurosurgery in children with fatal neurologic disease) concerns, this study design could not involve contemporaneous, matched, randomized, blinded, or untreated control subjects. As such, data from the DEM-CHILD Multi-Center Clinical NCL Database at the University Medical Center in Hamburg, Germany (NCT04613089) was used as a control group (i.e., Natural History [NH] comparator) to determine the primary efficacy outcome measures for this study. The control group (NH comparator) was comprised of subjects from the DEM-CHILD database who satisfied the 190-201 inclusion criterion: Age ≥ 3, and at least one ML score ≥ 3 at age ≥ 3 years and further, who had at least two CLN2 assessments with values within the range 1 - 5 and at least 6 months apart. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age immediately preceding the first 300 mg infusion. Data for Study 190-201, was recorded as the number of complete (integer) years lived at the time of study enrollment. Data presented for 190-201/202 is based on derived age (continuous variable) using the baseline date compared to the date of birth considering both month and year of birth. The change from reporting "age at enrollment" for 190-201 to reporting "age at baseline" for 190-201/202 was made to align with the reported outcome measure of baseline ML score. | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| 300 mg Baseline ML Score | The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first 300 mg 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). | Mean | Standard Deviation | units on a scale |
|
| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Probability of Unreversed 2-point Decline in Motor-language (ML) Score or Score of 0 | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function. In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (i.e., baseline ML score and age as continuous covariates, and genotype [common alleles] and sex as categorical covariates). | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). NH: 42 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description below. | Posted | Number | 95% Confidence Interval | Probability of decline | Up to Week 289 |
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| Primary | Probability of Unreversed Motor-language (ML) Score of Zero. | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function. In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (baseline ML score, age, genotype [common alleles], and sex). | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). NH: 42 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description below. | Posted | Number | 95% Confidence Interval | Probability of decline | Up to Week 289 |
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| Secondary | Whole Brain Volume | Percentage change from Baseline to Last Observation: Whole Brain volume | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). | Posted | Mean | Standard Deviation | percentage change | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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| Secondary | Volume of Cerebrospinal Fluid | Percentage Change from Baseline to last observation: Volume of cerebrospinal fluid | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). | Posted | Mean | Standard Deviation | percentage change | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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| Secondary | Volume of Total Cortical Gray Matter | Percentage Change from Baseline to last observation: Volume of total cortical gray matter | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). | Posted | Mean | Standard Deviation | percentage change | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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| Secondary | Total White Matter Volume | Percentage Change from Baseline to last observation: Total white matter volume | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). | Posted | Mean | Standard Deviation | percentage change | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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| Secondary | Whole Brain Apparent Diffusion Coefficient | Change from Baseline to last observation Whole brain apparent diffusion coefficient | BMN 190-202: 24 subjects were enrolled in 190-201 at 5 clinic sites worldwide. One subject terminated from 190-201 after a single infusion and is not included in the Intent-to-Treat (ITT) population for 190-202. Study 190-202 final efficacy results include pooled data from the complete dataset from Study 190-201 & Study 190-202 for all subjects who received >1 dose (N=23). | Posted | Mean | Standard Deviation | mm^2/s | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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Summaries of safety data were descriptive and designed to be inclusive of all adverse events reported in both the 190-201 and 190-202 studies. For each subject, adverse event (AE) data were collected from ICV access device implantation in Study 190-201, prior to any dose administration, to either 6 months after the last administration of study drug or the early termination visit in Study 190-202.
190-202 is the extension of treatment and follow-up for patients who enrolled in 190-201. Pooled data are presented since AE data for 190-202 were collected starting with ICV access device implantation in 190-201 (prior to any dose administration). Subjects who experienced more than 1 AE within a given MedDRA system organ class or preferred term were counted once within that system organ class or preferred term. Adverse events and deaths were not collected for Natural History participants.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BMN 190-202 (300 mg) | Study 190-202 is the extension of treatment and follow-up for patients who enrolled in Study 190-201. Pooled data (Study 190-201/202; 24 subjects) are presented since adverse event data for Study 190-202 were collected starting with ICV access device implantation in Study 190-201 (prior to any dose administration). | 0 | 24 | 21 | 24 | 24 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Device related infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngitis bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Adenoviral upper respiratory infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Mycoplasma infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngotonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Propionibacterium infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Device end of service | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device leakage | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device malfunction | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Pleocytosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Motor dysfunction | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Status epilepticus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Device deployment issue | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Adenoidal hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Blindness | Eye disorders | MedDRA 20.0 | Systematic Assessment |
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| CSF culture positive | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Acidosis | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
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| Tooth extraction | Surgical and medical procedures | MedDRA 20.0 | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abasia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Complication associated with device | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Developmental delay | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Feeling jittery | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Device deployment issue | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Device difficult to use | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Stoma site reaction | Injury, poisoning and procedural complications | 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 |
| |
| Oxygen saturation decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| CSF test abnormal | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Extensor plantar response | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myoclonus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Petit mal epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pleocytosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Speech disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Language disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyskinesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Athetosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Atonic seizures | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myoclonic epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Movement disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure cluster | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Clonus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chorea | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Drop attacks | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypotonia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Blindness | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Teething | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Device end of service | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device leakage | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Needle issue | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device malfunction | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Device issue | Product Issues | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Epstein-Barr virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pharyngitis bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillitis bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Varicella | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Otitis media | 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 | |
|---|---|---|---|---|
| Trial Specialist | BioMarin Pharmaceutical, Inc. | 1-800-983-4587 | medinfo@bmrn.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 10, 2021 | Dec 9, 2021 | 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 |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Probability of decline: Week 145 |
|
| Probability of decline: Week 193 |
|
| Probability of decline: Week 241 |
|
| Probability of decline: Week 289 |
|
| OG001 | Natural History Comparator | The control group (NH comparator) was comprised of subjects from the DEM-CHILD database who satisfied the 190-201 inclusion criterion: Age ≥ 3, and at least one ML score ≥ 3 at age ≥ 3 years and further, who had at least two CLN2 assessments with values within the range 1 - 5 and at least 6 months apart. |
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