Study Of Safety, Tolerability And Pharmacokinetics Of Subcutaneous Doses Of TA-46
Study Of Safety, Tolerability And Pharmacokinetics Of Subcutaneous Doses Of TA-46
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
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.
Inclusion Criteria:-

 -  Age : 21-55 years, inclusive, at screening

 -  Weight : maximum weight of 100 kg

 -  Normal height without any growth complications during childhood

 -  Healthy as determined by screening assessments

 Exclusion Criteria:

 -  Concomitant disease or condition that could interfere with, or for which the treatment
 might interfere with, the conduct of the study, or that would, in the opinion of the
 PI, pose an unacceptable risk to the subject in this study

 -  Clinically significant abnormalities in laboratory test results (including hepatic and
 renal panels, complete blood count, chemistry panel and urinalysis)

 -  Participation in an investigational drug or device study within 3 months prior to (the
 first) drug administration in the current study