An Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
Condition: Jansky-Bielschowsky Disease; Batten Disease; Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2; CLN2 Disease; CLN2 Disorder
MeSH terms: Neuronal Ceroid-Lipofuscinoses
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): BMN 190; Intracerebroventricular (ICV) access device
Intervention type(s): Biological; Device
Intervention description(s): 300 mg Intracerebroventricular (ICV) infusion administered every other week for up to 240 weeks; Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.
Other intervention name(s): recombinant human tripeptidyl peptidase-1 (rhTPP1); cerliponase alfa
Intervention model: Single Group Assignment
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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Late infantile Neuronal Ceroid Lipofuscinosis Type 2; LINCL; NCL2; CLN2; Jansky-Bielschowsky disease