Clinical trial NCT04410809: Study Of Safety, Tolerability And Pharmacokinetics Of Subcutaneous Doses Of TA-46
Official title: A SINGLE-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY INVESTIGATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF SINGLE- AND MULTIPLE-ASCENDING SUBCUTANEOUS DOSES OF TA-46 IN HEALTHY VOLUNTEERS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-06-01
Enrollment: 78
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Bsseline to Day 43 after last dose of study medication
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Baseline up to Day 43 after last dose of study medication
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Baselin up to Day 43 after last dose of study medication
measure: Number of Participants With Change From Baseline in Physical Examinations and Vital Signs
timeFrame: Baseline up to Day 43 after last dose study medication
measure: Number of Participants With Abnormal Electrocardiogram (ECG)
timeFrame: Baseline up to Day 22 after last dose of study medication
Secondary outcomes:
measure: Area under the Concentration-Time Curve (AUC)
timeFrame: BaselineDay 1, Day , Day 15, Day 22 & Day 25, Day 29 post dose
measure: Cmax
timeFrame: Baseline, Day 1, Day , Day 15, Day 22 & Day 25, Day 29 post dose
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: