Clinical trial NCT02485899: An Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
Official title: A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Jansky-Bielschowsky Disease
Batten Disease
Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
CLN2 Disease
CLN2 Disorder
Keywords: Late infantile Neuronal Ceroid Lipofuscinosis Type 2
LINCL
NCL2
CLN2
Jansky-Bielschowsky disease
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 23
Sex: ALL
Minimum age (years): 3
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Must have completed 48 weeks in Study 190-201.
* Is willing and able to provide written, signed informed consent. Or, in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
* Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study.
* If female, of childbearing potential, must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests done during the study.

Exclusion Criteria:

* Has had a loss of 3 or more points in the combined motor and language components of the Hamburg CLN2 rating scale between Baseline of Study 190-201 and the Study Completion visit in Study 190-201 and would not benefit from enrolling in the study in the Investigator's discretion.
* Has a score of 0 points on the combined motor and language components of the Hamburg CLN2 rating scale.
* Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
* Has used any investigational product (other than BMN 190 in 190-201), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
* Has a concurrent disease or condition that would interfere with study participation, or pose a safety risk, as determined by the Investigator.
* Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Primary outcomes:
measure: Probability of Unreversed 2-point Decline in Motor-language (ML) Score or Score of 0
timeFrame: Up to Week 289
measure: Probability of Unreversed Motor-language (ML) Score of Zero.
timeFrame: Up to Week 289
Secondary outcomes:
measure: Whole Brain Volume
timeFrame: Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
measure: Volume of Cerebrospinal Fluid
timeFrame: Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
measure: Volume of Total Cortical Gray Matter
timeFrame: Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
measure: Total White Matter Volume
timeFrame: Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
measure: Whole Brain Apparent Diffusion Coefficient
timeFrame: Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Rome
country: Italy
facility: Children's Hospital Bambino Gesù,IRCCS
state: Piazza
city: London
country: United Kingdom
facility: Great Ormond Street Childrens Hospital
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.