A Study of PRA023 in Healthy Volunteers

Study Overview
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Brief Summary
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This is randomized, double-blind, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRA023 in healthy volunteers.

Official Title
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A Phase 1, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetics Study of PRA023 in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: PRA023
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (of non-childbearing potential only) between minimum adult legal age (according to local laws for signing the informed consent document) and 55 years of age. Females must be of non-childbearing potential and must have undergone one of the following sterilization procedures, and have official documentation, at least 6 months prior to the first dose: hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy, or; be postmenopausal with amenorrhea for at least 1 year prior to the first dose and have FSH serum levels consistent with postmenopausal status as per investigator judgment. Male subjects must use reliable forms of contraception during sexual intercourse with female partners from screening to 30 days after the end of dosing. Good general health as determined by medical history, and by results of physical examination, chest x-ray, vital signs, ECG, and clinical laboratory tests obtained within 28 days (4 weeks) prior to study drug administration. Exclusion Criteria: History or presence of any clinically significant organ system disease that could interfere with the objectives of the study or the safety of the subjects. Blood pressure and heart rate are outside the ranges 90-140 mmHg systolic, 60-90 mmHg diastolic, heart rate 60-100 beats/min. 12-lead ECG with any abnormality judged by the Investigator to be clinically significant, QRS >= 120 milliseconds (msec), or QTcF interval of > 450 msec for men or >470 msec for women. Presence or history of any abnormality or illness, which in the opinion of the Investigator may affect absorption, distribution, metabolism or elimination of the study drug. Any screening laboratory evaluation outside the laboratory reference range that is judged by the Investigator to be clinically significant. History of or current active tuberculosis (TB) infection; history of latent TB that has not been fully treated or current latent TB infection as indicated by a positive QuantiFERON-TB test. History of significant allergy to any medication as judged by the Investigator. History of alcohol or drug abuse within the past 24 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD Cohorts 1-6 Experimental Arm<br>Subjects will receive single intravenous doses of PRA023 in a dose escalation format | Drug: PRA023<br>* PRA023<br>|
| Placebo Comparator: SAD Cohorts 1-6 Placebo Arm<br>Subjects will receive intravenous doses of placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: MAD Cohorts 1-5 Experimental Arm<br>Subjects will receive three intravenous doses of PRA023, one dose every 2 weeks, in a dose escalation format | Drug: PRA023<br>* PRA023<br>|
| Placebo Comparator: MAD Cohorts 1-5 Placebo Arm<br>Subjects will receive three intravenous doses of placebo, one dose every 2 weeks, | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events | Incidence, severity, and causal relationship of TEAEs | Up to 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration after single and multiple ascending doses | Up to 22 weeks | 
| Tmax | Time to reach maximum concentration after single and multiple ascending doses | Up to 22 weeks | 
| t1/2 | Half life after single and multiple ascending doses | Up to 22 weeks | 
| AUC | Area under the curve after single and multiple ascending doses | Up to 22 weeks | 
| ADA | Incidence of anti-drug antibody after single and multiple ascending doses | Up to 22 weeks |