Systemic administration of the antisense oligonucleotide NS ‐089/ NCNP ‐02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/ II clinical trial

Figures

• 

  FIGURE 1. Study design and flow. In Part 1, the dose of NS‐089/NCNP‐02 will be escalated in a stepwise manner from Level 1 (1.62 mg/kg QW) to Level 4 (80 mg/kg QW). A total of four doses will be intravenously administered to two cohorts consisting of three subjects each, and each cohort will receive two doses. In Part 2, two doses of NS‐089/NCNP‐02 (determined from the results of Part 1) will be intravenously administered once weekly for 24 weeks. QW, once weekly.

• 

  FIGURE 2. Study observations and examinations: implementation schedules. (A) Part 1; (B) Part 2. aPatients who complete Level 1 or 2 and proceed to Level 3 or 4 will not have a pre‐treatment observation period prior to the administration at Level 3 or 4 but will have their height/weight measured during the period between Days −7 and −1 before administration of NS‐089/NCNP‐02. bConsent may be obtained before the day of interim enrollment. cInterim enrollment. After obtaining informed consent, the investigator or sub‐investigator will confirm that the patient is a candidate for exon 44 skipping treatment and enroll the patient. The results of exon 44 sequence analysis shall be confirmed before formal enrollment. dFormal enrollment. Patients will be enrolled after confirming examination results obtained within 14 days before the start of administration of NS‐089/NCNP‐02. Formal enrollment on the day before the first administration may be accepted. eTo be performed at the end of administration and at 2 h after the end of administration. fTo be performed at the following times: 30 min after the start of administration on Day 1; at the end of administration on Day 1; at 1, 2, 4, and 6 h after…