Study Of Safety, Tolerability And Pharmacokinetics Of Subcutaneous Doses Of TA-46
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      TA-46 single- and multiple-ascending dose study in healthy volunteers to investigate safety
      and PK. The protocol is conducted in four parts; Part A - Single Ascending doses of TA46 Part
      B - Multiple Ascending doses of TA-46 Part C - Comparing 2 formulations 50mg/ml vs 120mg/ml
      TA-46 Part D - Single Ascending dose of TA46 120mg/ml formulation

      The subjects will be in the clinic for 1 period. The subjects will be admitted to the
      clinical research center in the afternoon of Day -1. They will be discharged on Day 4 (72
      hours post-dose) after completion of the assessments. After discharge, the subjects will
      return to the clinical research center for ambulatory visits on Days 5, 8, 10, 12, 14 and 22
    

Detailed description: 
      This is a single-center, 34-part clinical study in healthy subjects.

      Part A This is a single-center, double-blind, randomized, placebo-controlled, single
      ascending dose study in healthy subjects. The dose escalation is adaptive in nature. An
      estimated number of 5 dose levels will be administered in Part A of the study, with at each
      dose level 6 subjects randomized to receive TA-46 and 2 to receive placebo. Depending on
      evaluation of the data the number of subjects may be adjusted and/or additional group(s) may
      be added.

      In this first-in-human study, the subjects participating at all dose levels of Part A (Groups
      A1-A5), will be dosed according to a sentinel dosing design to ensure optimal safety. This
      means that initially 2 subjects will be dosed: 1 subject with TA-46 and 1 subject with
      placebo. If the safety and tolerability results of the first 24 hours following dosing for
      the initial subjects are acceptable to the Principal Investigator (PI), the other 6 subjects
      (5 active and 1 placebo) of that dose level may be dosed.

      For Groups A1 and A2, TA-46 and placebo will be administered as a sc injection (bolus) and
      for Groups A3-A5, TA-46 and placebo will be administered as a sc infusion. When TA-46 and
      placebo will be administered as sc infusion, the duration of the sc infusion will be
      dependent on the volume to be administered, but will not exceed a period of 1 hour. The dose
      levels of TA-46 can be increased or decreased based on the results of the previous group(s).

      Part B This is a single-center, double-blind, randomized, placebo-controlled, multiple
      ascending dose study in healthy subjects. The dose escalation is adaptive in nature. TA-46
      will be administered twice weekly for4 weeks. An estimated number of 3 dose levels will be
      administered in Part B of the study, with at each dose level 6 subjects randomized to receive
      TA-46 and 2 to receive placebo. Depending on evaluation of the data the number of subjects
      may be adjusted and/or additional group(s) may be added. Based on the results of Groups B1
      and B2 of Part B, which followed a twice weekly dosing scheme for 4 weeks, the dosing scheme
      of Group B3 will be adapted to once weekly administration for 4 weeks and 31 additional
      groups (Groups B4 to B6) with the same dosing frequency will be added to Part B of the study.
      Depending on evaluation of the data, additional group(s) may be added or planned group(s) may
      be skipped.

      For Group B1, TA-46 and placebo will be administered as a sc injection (bolus) and for Groups
      B2 to B64, TA-46 and placebo will be administered as a sc infusion. When TA-46 and placebo
      will be administered as a sc infusion, the duration of the sc infusion will be dependent on
      the volume to be administered, but will not exceed a period of 1 hour. The dose levels of
      TA-46 can be increased or decreased based on the results of the previous group(s).

      Administration of a dose level in Part B can be started after completion and review of the
      corresponding or higher dose level in Part A of the study.

      Part C This is a single-center, single-dose, open-label, cross-over study in healthy subjects
      comparing 2 formulations of TA-46 (50 mg/mL and 120 mg/mL). A total of 6 subjects will
      receive Treatment A (TA-46 formulation 1) and Treatment B (TA-46 formulation 2) randomly
      assigned over 2 periods with 2 treatment sequences (Treatment A/B and Treatment B/A) with 3
      subjects per treatment in each sequence.

      The following treatments are planned to be administered according to the randomization code:

      Group C1 Treatment A: sc administration of 3 mg/kg TA-46 formulation 1 Treatment B: sc
      administration of 3 mg/kg TA-46 formulation 2TA-46 formulation 1 will be administered as a a
      sc infusion. The duration of the sc infusion will be dependent on the volume to be
      administered, but will not exceed a period of 1 hour. TA-46 formulation 2 will be
      administered as 1-2 sc injection(s) (bolus).

      The subjects will be in the clinic for 2 periods. Each period the subjects will be admitted
      to the clinical research center in the afternoon of Day -1 and they will be discharged on Day
      4 (72 hours post-dose) after completion of the assessments. After discharge, the subjects
      will return to the clinical research center for ambulatory visits on Days 6, 9, 12, 16, and
      22 of each period.

      Part D This is a single-center, open-label, single-dose study in healthy subjects with the
      TA-46 formulation of 120 mg/mL.

      TA-46 and placebo will be administered as a sc infusion. The duration of the sc infusion will
      be dependent on the volume to be administered, but will not exceed a period of 1 hour.
      Depending on evaluation of the data, additional group(s) may be added or planned group(s) may
      be skipped.
    

Intervention name(s): TA-46; Placebo
Intervention type(s): Biological; Other
Intervention description(s): Decoy protein of the fibroblast growth factor receptor 3, 50 mg/mL (Parts A, B and C) and 120 mg/mL (Part C and Part D), sc solution for injection/infusion; The same composition as the active medication but without the active substance TA-46
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment