Phase 1 Single Dose Study of ALXN1101 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Phase 1 single dose study of ALXN1101 in healthy volunteers.

Detailed Description
-----------------
This is a first-in-human (FIH), randomized, blinded, placebo-controlled, single-dose, sequential-cohort, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single dose of ALXN1101 in healthy adult subjects.

Official Title
-----------------
A Phase 1, Randomized, Blinded, Placebo-Controlled, Single-Dose, Sequential-Cohort, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ALXN1101 in Healthy Adult Subjects

Conditions
-----------------
Molybdenum Cofactor Deficiency (MoCD), Rare Autosomal Recessive Disorder, Deficiency of Activity of Molybdenum-dependent Enzymes (Sulfite Oxidase [SOX], Xanthine Dehydrogenase, and Aldehyde Oxidase)

Intervention / Treatment
-----------------
* Drug: ALXN1101
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Male or female subjects ≥ 18 and ≤ 60 years of age and weight ≥ 55 kg and ≤ 100 kg Willing and able to give written informed consent Female subjects of child bearing potential must have a negative serum pregnancy test or must be practicing an approved contraceptive regimen for the duration of the study Male subjects must be practicing an acceptable barrier method of contraception Key Exclusion Criteria: Pregnant or nursing female subjects QTcF > 450 msec for males and > 470 msec for females, or a family history of Long QT Syndrome. CrCl < 80 mL/min CBC in acceptable range; SGOT or SGPT above the ULN HIV, Hepatitis B or Hepatitis C virus infection Other active systemic infection or malignancy Investigational drug study within 60 days Major surgery within the prior 90 days History of illicit drug use or chronic alcohol dependence within 2 years prior to this study Positive urine drug toxicology screen or serum alcohol test Alcohol consumption within 48 hours prior to study drug administration Recently donated or lost ≥ 499 mL of blood Recent hormone replacement therapy or use of prescription medications

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1101<br>Four cohorts planned. Within each cohort, healthy volunteers are randomized to ALXN1101 IV single dose or placebo IV single dose. Each subsequent cohort is testing an increased dose of ALXN1101 IV or placebo IV. | Drug: ALXN1101<br>* Randomized to receive a single dose of ALXN1101 or placebo as per assigned cohort dose level.<br>|
| Placebo Comparator: Placebo<br>Four cohorts planned. Within each cohort, healthy volunteers are randomized to ALXN1101 IV single dose or placebo IV single dose. Each subsequent cohort is testing an increased dose of ALXN1101 IV or placebo IV. | Drug: Placebo<br>* Randomized to receive a single dose of ALXN1101 or placebo as per assigned cohort dose level.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single dose of ALXN1101 in healthy adult subjects | Physical examination, vital signs, ECGs, laboratory evaluations, and Adverse Events. | following the Day 30 visit for the last study subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of ALXN1101 | PK parameters of ALXN1101 will be estimated including, but not limited to,maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (tmax), terminal elimination halflife (t½), area under the plasma concentration-time curve (AUC), total body clearance (CL), and volume of distribution (Vd). | following the Day 5 visit for the last study subject | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
molybdenum cofactor deficiency (MoCD), deficiency of activity of molybdenum-dependent enzymes