Jansky-Bielschowsky DiseasePhase 1/2NCT01907087

A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease

A Phase 1/2 study testing BMN 190 in people with Jansky-Bielschowsky Disease and Batten Disease, run by BioMarin Pharmaceutical at 5 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 15 years
Conditions the study is for: Jansky-Bielschowsky Disease, Batten Disease, Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
What is being tested?: BMN 190
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 5 sitesin 4 countries
Study dates: Sep 2013to Nov 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 15 years
All sexes
No healthy volunteers
Child

Who may be able to join

Has a diagnosis of CLN2 determined by TPP1 enzyme activity (dried blood spot) available at study entry. If no genotype information is available, blood will be collected for CLN2 gene analysis at baseline. In addition, blood for TPP1 enzyme activity (dried blood spot) will be collected at baseline to be analyzed centrally
Has mild to moderate disease documented by a two-domain score of 3- 6 on motor and language domains of the Hamburg Scale, with a score of at least 1 in each of these two domains
Written informed consent from parent or legal guardian and assent from subject, if appropriate
Has the ability to comply with protocol requirements, in the opinion of the investigator
Seizures are stable in the judgement of the investigator

Who cannot join

Is less than 3 years old at enrollment
Is 16 years old or older at enrollement
Has another inherited neurologic disease, e.g. other forms of CLN or seizures unrelated to CLN2 (patients with febrile seizures may be eligible)
Has another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) before study entry
Requires ventilation support, except for noninvasive support at night
Has received stem cell, gene therapy, or ERT for CLN2

Show all 15Show fewer

Has contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)
Has contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
Has generalized motor status epilepticus within 4 weeks before the First Dose visit, taking care that status epilepticus is on clinical examination and not only electroencephalogram (EEG) (enrollment may be postponed)
Has severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed)
Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts
Has known hypersensitivity to any of the components of BMN 190
Has received any investigational medication within 30 days before the first infusion of study drug or is scheduled to receive any investigational drug other than BMN 190 during the course of the study
Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's well being, safety, or clinical interpretability
Pregnancy any time during the study

Trial locations and contacts

5 sites in 4 countries.

Country

City, postcode or hospital

5 sites in 4 countries

United Kingdom2 sites

Guy's & St. Thomas NHS Foundation Trust
London, SE1 7EH
Great Ormond Street Hospital for NHS Foundation Trust
London, WC1N 3JH

Other trials in United Kingdom

United States1 site

Nationwide Children's Hospital
Columbus, Ohio, 43205

Other trials in United States

Germany1 site

University Hamburg-Eppendorf
Hamburg, 20246

Other trials in Germany

Italy1 site

Bambino Gesù Children's Hospital
Rome, 00165

Other trials in Italy

About this study

Official title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease

The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease.

Read the detailed description

The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease. This is an open label Phase 1/2 study conducted in patients with CLN2 disease. Efficacy measures (disease rating scale and MRI) will be compared to a natural history control.

The study will be conducted under cGCP and patients will be closely monitored.

Conditions: Jansky-Bielschowsky Disease, Batten Disease, Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2, CLN2 Disease
Being tested: BMN 190
Keywords: Late infantile Neuronal Ceroid Lipofuscinosis Type 2, LINCL, NCL2, CLN2, Jansky-Bielschowsky disease
Medical subject headings: Neuronal Ceroid-Lipofuscinoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BMN 190Biological
Also called recombinant human tripeptidyl peptidase-1 (rhTPP1), cerliponase alfa
30-300 mg ICV infusion administered every other week for at least 48 weeks.

Study groups in NCT01907087
Study group	Role	What they receive
BMN190	Experimental	recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa) Receives: Biological: BMN 190

What is being measured

The primary outcome is the main question the study is designed to answer.

Motor-Language (ML) Scale Score During 300 mg Dosing Period
The progression of ceroid lipofuscinosis (CLN2) disease was assessed using adapted motor and language domains of the Hamburg rating scale (ML scale score). Motor and Language are each 0 - 3 point subscales in which 3 represents best function and 0 represents loss of function. The sum of the motor and language scores (ML score, 0-6 points) was used to evaluate the loss of function.
Measured: Baseline, Week 49/Last Assessment

Secondary outcomes (5)

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Volume
Percentage changes in whole brain volume from the ITT population for the 300 mg dosing period
Measured: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Total Grey Matter
Percentage changes in volume of total grey matter from the ITT population for the 300 mg dosing period
Measured: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Total White Matter Volume
Percentage changes in total white matter volume from the ITT population for the 300 mg dosing period
Measured: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Cerebrospinal Fluid
Percentage changes in volume of cerebrospinal fluid from the ITT population for the 300 mg dosing period
Measured: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Apparent Diffusion Coefficient
Percentage changes in whole brain apparent diffusion coefficient from the ITT population for the 300 mg dosing period
Measured: Baseline, Week 49

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2013Nov 2015

First posted24 Jul 2013 (estimated)
Study startSep 2013
Primary completionNov 2015
Study completionNov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Jansky-Bielschowsky DiseaseStudies of the same condition, open and under way.
More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01907087
Sponsor's protocol ID: 190-201
Status last verified: Mar 2019
First submitted: 19 Jul 2013
Last updated: 8 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 38776275
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.
PubMed 38101904
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.
PubMed 33980287
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.
PubMed 29688815

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Registrational Study of TTX-381 to Treat Vision Loss in CLN2 Disease
Neuronal Ceroid Lipofuscinosis Type 2
Active, not recruitingObservational study
Cerliponase Alfa Observational Study in the US
Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
Not yet recruitingPhase 1/2
Gene Therapy Trial for CLN6 Batten Disease
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Active, not recruitingPhase 1/2
Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
Neuronal Ceroid Lipofuscinosis Type 2
Active, not recruitingObservational study
Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients
Neuronal Ceroid-Lipofuscinoses, Neuronal Ceroid Lipofuscinosis CLN2

All Jansky-Bielschowsky Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease
ClinicalTrials.gov ID: NCT01907087
Acronym / sponsor ID: 190-201
Conditions: Jansky-Bielschowsky Disease, Batten Disease, Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2, CLN2 Disease
Keywords: Late infantile Neuronal Ceroid Lipofuscinosis Type 2, LINCL, NCL2, CLN2, Jansky-Bielschowsky disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
Study start: Sep 2013
Primary completion: Nov 2015 (actual)
Study completion: Nov 2015 (actual)
First posted: 24 Jul 2013 (estimated)
Results: Posted 11 Jun 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease.

Detailed description

The study will be conducted under cGCP and patients will be closely monitored.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BMN190	Experimental	Biological: BMN 190recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa)

Who may qualify

Ages: 3 to 15 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Has a diagnosis of CLN2 determined by TPP1 enzyme activity (dried blood spot) available at study entry. If no genotype information is available, blood will be collected for CLN2 gene analysis at baseline. In addition, blood for TPP1 enzyme activity (dried blood spot) will be collected at baseline to be analyzed centrally
Has mild to moderate disease documented by a two-domain score of 3- 6 on motor and language domains of the Hamburg Scale, with a score of at least 1 in each of these two domains
Written informed consent from parent or legal guardian and assent from subject, if appropriate
Has the ability to comply with protocol requirements, in the opinion of the investigator
Seizures are stable in the judgement of the investigator

Key exclusion criteria (15 listed)

Is less than 3 years old at enrollment
Is 16 years old or older at enrollement
Has another inherited neurologic disease, e.g. other forms of CLN or seizures unrelated to CLN2 (patients with febrile seizures may be eligible)
Has another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) before study entry
Requires ventilation support, except for noninvasive support at night

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BMN 190Also: recombinant human tripeptidyl peptidase-1 (rhTPP1), cerliponase alfa30-300 mg ICV infusion administered every other week for at least 48 weeks.	Biological	BMN190

Primary outcome

Motor-Language (ML) Scale Score During 300 mg Dosing Period
Time frame: Baseline, Week 49/Last Assessment
The progression of ceroid lipofuscinosis (CLN2) disease was assessed using adapted motor and language domains of the Hamburg rating scale (ML scale score). Motor and Language are each 0 - 3 point subscales in which 3 represents best function and 0 represents loss of function. The sum of the motor and language scores (ML score, 0-6 points) was used to evaluate the loss of function.

5 secondary outcomes

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Volume
Time frame: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Total Grey Matter
Time frame: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Total White Matter Volume
Time frame: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Cerebrospinal Fluid
Time frame: Baseline, Week 49
Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Apparent Diffusion Coefficient
Time frame: Baseline, Week 49

Results and safety

Results posted to the registry on 11 Jun 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
300 mg BMN 190	24	23

Primary outcome: Motor-Language (ML) Scale Score During 300 mg Dosing Period

Time frame: Baseline, Week 49/Last Assessment. Mean (Standard Deviation). Unit: units on a scale

Measure	300 mg BMN 190 n = 23
Baseline	3.5 (1.2)
Last Recorded Observation	3.1 (1.41)
Change from Baseline to Last Recorded Observation	-0.4 (0.84)

300 mg BMN 190: Proportion of responders: 0.87 (95% CI 0.66 to 0.97), p = 0.0002, exact binomial test
300 mg BMN 190: Slope: 0.4 (95% CI 0.05 to 0.75), p <0.0001, t-test, 2 sided

Population analysed: Intent to Treat (ITT) Population : all study subjects receiving \> 1 dose

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Full study period, a mean of 49 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
300 mg BMN 190	16 of 24 (66.7%)	24 of 24 (100%)	0 of 24

Limitations and caveats (from the sponsor): 10 subjects were assigned in 1 of 3 cohorts in Dose Escalation Period for a 4-22 weeks treatment of 30, 100, and/or 300 mg. 9 subjects completing the Dose Escalation Period, plus 14 new subjects, were administered a stable dose of 300mg for 48 weeks.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38776275Specchio 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.
Derived from this study: PubMed 38101904Schulz 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.
Derived from this study: PubMed 33980287Gissen 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.
Derived from this study: PubMed 29688815Schulz 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.

Related trials for Jansky-Bielschowsky Disease

RecruitingPhase 1/2
A Registrational Study of TTX-381 to Treat Vision Loss in CLN2 Disease
Neuronal Ceroid Lipofuscinosis Type 2
Active, not recruitingObservational study
Cerliponase Alfa Observational Study in the US
Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
Not yet recruitingPhase 1/2
Gene Therapy Trial for CLN6 Batten Disease
CLN6, Batten Disease
Active, not recruitingPhase 1/2
Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
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Active, not recruitingObservational study
Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients
Neuronal Ceroid-Lipofuscinoses, Neuronal Ceroid Lipofuscinosis CLN2

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Jacoby study director

BioMarin Pharmaceutical

5 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BMN 190 in people with Jansky-Bielschowsky Disease and Batten Disease, run by BioMarin Pharmaceutical at 5 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom, United States, Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Motor-Language (ML) Scale Score During 300 mg Dosing Period (time frame: Baseline, Week 49/Last Assessment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01907087, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2019.