an efficacy and safety study of hgt-1110 in participants with metachromatic leukodystrophy

Conditions: Metachromatic Leukodystrophy (MLD)

Summary: the purpose of this study is to collect long-term safety data in participants with metachromatic leukodystrophy (mld) who are receiving hgt-1110 and have participated in study hgt-mld-070 (nct01510028) through week 40.

mld is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase a (asa). mld is a rare orphan disease that occurs in most parts of the world. the estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births that varies by geographic location. there are no approved therapies for mld. this study is a multicenter open-label study designed to evaluate safety and efficacy outcomes of hgt-1110 administered intrathecally in children with mld who have participated in the dose escalation study, hgt-mld-070 (nct01510028), through week 40 and are receiving study drug every other week (eow). treatment groups will be identical to those in hgt-mld-070 (nct01510028), ie, participants assigned to cohort 1 in study hgt-mld-070 (nct01510028) will continue to receive a dose of 10 milligrams (mg), participants assigned to cohort 2 in study hgt-mld-070 (nct01510028) will continue to receive a dose of 30 mg, and participants assigned to cohorts 3 and 4 in study hgt-mld-070 (nct01510028) will continue to receive a dose of 100 mg. participants in cohort 4 are to exclusively receive drug product produced with process b in study hgt-mld-070 (nct01510028) and will continue receiving this drug product in this study. participants enrolled in this study from cohorts 1 to 3 in study hgt-mld-070 (nct01510028) were transitioned to process b after all necessary approvals were obtained. in hgt-mld-071, all participants in the 10 mg dose cohort who experienced disease progression, as determined by the investigator, increased to the 30 mg dose after agreement by the medical monitor. based on the interim analysis results from hgt-mld-070 (nct01510028 \[cohorts 1-3\]), the dose of hgt-1110 will be increased to 100 mg for all participants in hgt-mld-071 after all necessary approvals were obtained.

Eligibility criteria:
inclusion criteria: 1. participant has participated in study hgt-mld-070 (nct01510028) through week 40. 2. participant must have no safety or medical issues that contraindicate participation. 3. the participant, participant's parent(s), or legally authorized representative(s) must provide written informed consent and/or assent (if applicable) prior to performing any study-related activities. exclusion criteria: 1. the participant is unable to comply with the protocol (example, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the investigator. 2. undergoes bone marrow transplant (bmt), hematopoietic stem cell transplantation (hsct), or gene therapy at any point during the study. 3. the participant has any known or suspected hypersensitivity to agents used for anesthesia or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions. 4. the participant is pregnant or breastfeeding. 5. the participant is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or drug delivery device) other than those used in hgt-mld-070 (nct01510028) within 6 months prior to study enrollment or at any time during the study. 6. the participant has a condition that is contraindicated as described in the soph-a-port mini siddd instructions for use (ifu), including: 1. the participant has had, or may have, an allergic reaction to the materials of construction of the soph-a-port mini s device. 2. the participant's body size is too small to support the size of the soph-a-port mini s access port, as judged by the investigator. 3. the participant has a known or suspected local or general infection. 4. the participant is at risk of abnormal bleeding due to a medical condition or therapy. 5. the participant has one or more spinal abnormalities that could complicate safe implantation or fixation. 6. the participant has a functioning csf shunt device. 7. the participant has shown an intolerance to an implanted device.