Safety Study of Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Traumatic Brain Injury: Dosing Tier 1

Study Overview
=================
Brief Summary
-----------------
Prospective, Open Label, Cohort Study in Traumatic Brain Injury Patients. The goal of this study is to assess the safety of NTx®-265. NTx®-265 will be administered over 9 days, and patients will be followed for an additional 6 months.

Official Title
-----------------
A Phase IIa, Single Centre, Open Label Study to Characterize the Safety of Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Traumatic Brain Injury: Dosing Tier 1

Conditions
-----------------
Traumatic Brain Injury

Intervention / Treatment
-----------------
* Drug: NTx 265


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients age 18-65 Written and informed consent from a legally acceptable representative Moderate to severe traumatic brain injury (TBI) defined as Glasgow Coma motor (GCSm) score ≤5, post resuscitation. Patient is <48hours from time of injury when the first dose of NTx™-265 is administered. Reasonable expectation of availability to receive the full 9 day course of therapy and be available for follow up evaluations Female patient is either: Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral oophorectomy or hysterectomy) or If of childbearing potential, would agree to use two of the following reliable methods of birth control throughout the study, including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device A vasectomised partner Abstinence Note: Hormonal Based contraceptives are NOT permissible as one of the two forms of contraceptives for this study. Exclusion Criteria: Women who have been tested positive for pregnancy, or are breast-feeding or are not using a highly effective method of birth control that can be maintained for the duration of the study. Bilaterally fixed pupils Serum hemoglobin >160g/L (males) or >140g/L (female); or platelet count > 400,000/mm3 Advanced cardiac, pulmonary, hepatic or liver disease; the former will be operationally defined using NCI Toxicity Criteria (Grade 2 or higher). Suspected anoxic or ischemic brain injury Known endocrine or germ cell tumor Serum billirubin > 1.5 x upper limit of normal (ULN). Alkaline Phosphatase > 2.5 x ULN AST and/or ALT > 2.5 x ULN Creatinine > 2.0 x ULN Patients with known or documented transferrin saturation < 20% or ferritin < 100ng/mL. Male patients with known and documented elevated PSA levels, or a PSA level of ≥4ng/mL at screening. Patients with known history or hypercoagulability, including known cardiolipin/antiphospholipid antibody syndrome. Allergy or other contraindication to hCG including: Prior hypersensitivity to hCG preparations or one of their excipients. Primary ovarian failure. Uncontrolled thyroid or adrenal dysfunction. An uncontrolled organic intracranial lesion such as a pituitary tumor. Abnormal uterine bleeding of undetermined origin. Ovarian cyst or ovarian enlargement of undetermined origin. Sex hormone dependent tumors of the reproductive organs, accessory sex glands, and breasts. Allergy or other contraindication to epoetin alfa: Who developed pure red cell aplasia following treatment with any erythropoiesis regulating hormones. With uncontrolled hypertension With known hypersensitivity to mammalian cell-derived products, albumin (human) or any component of the product Who for any reason cannot receive adequate antithrombotic treatment A known diagnosis of cancer (except basal cell cancer). Uncontrolled hypertension, defined as blood pressure persistently above 220 mm Hg systolic or 120 mm Hg diastolic despite antihypertensive therapy. Use of either hCG or epoetin alfa within the previous 90 days. Any condition known to elevate hCG, active in the prior 24 months e.g., choriocarcinoma or germ cell tumor. Any patients living in a nursing home or supervised living center. Patients must be historically fully independent in all activities of daily living including banking, shopping, cooking, toileting, showering and dressing. Any other medical condition, in the investigator's opinion, the patient should not be included in the trial. Patients who cannot take anti-platelet or anti-coagulant therapy. Pre-existing and active major psychiatric or other chronic Neurological disease. Patients who have a history of substance abuse or dependency within 12 months prior to the study. Currently participating in another investigational study Polytrauma defined as an Abbreviated Injury Severity Score >3 in any area other than head. Patients with evidence of an active or previous thrombotic event. Patients with contraindications to MRI scans Patients who are currently taking hormonal based contraceptives or hormonal replacement therapy in the past three (3) months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTx 265<br> | Drug: NTx 265<br>* 10,000IU of hCG, every other day for three doses followed by 4000IU once daily for three days of erythropoietin<br>* Other names: Ovidrel, Serono;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The primary endpoint for this study is safety. The following safety endpoints will be assessed: Type, incidence, severity, timing, seriousness, and relatedness of adverse events. Lower extremity deep vein ultrasound will be performed to identify and localize deep or superficial venous thrombosis. Vital signs Laboratory assessments. Particular attention will be paid to serial hemoglobin and hematocrit measurements. DVT, PE, thromboembolism, MI and stroke. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | The following secondary endpoints will also be assessed in order to measure various aspects of neurological status: GOSE at hospital discharge, 3, and 6 months post-TBI Neurobehavioral Rating Score at hospital discharge, 3, and 6 months post TBI Disability Rating Score at hospital discharge, 3, and 6 months post TBI | 6 months |