REGENESIS (CA): A Study of NTx™-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Acute Ischemic Stroke Patients

Stroke Clinical Trial

— REGENESIS  

Official title:

A Phase IIb Prospective, Randomized, Double-blind, Placebo Controlled Study of NTx™-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Acute Ischemic Stroke Patients (REGENESIS)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00663416
• Other study ID #: NTx™-265-CP-201-IS (CA)
• Status: Terminated
• Phase: Phase 2
• First received: April 18, 2008
• Last updated: August 10, 2009
• Start date: March 2008
• Est. completion date: January 2009

Study information

• Verified date: August 2009
• Source: Stem Cell Therapeutics Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Ethics Review CommitteeIndia: Drugs Controller General of IndiaIndia: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Primary objective: To assess the neurological outcome in acute ischemic stroke patients treated with NTx™-265, when compared with patients given a placebo control.

Secondary objective: To assess the safety and tolerability of NTx™-265 when given to acute ischemic stroke patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 134
• Est. completion date: January 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Age 18-85.

• NIHSS score 6-24 within 24-48 hours after stroke onset and enrolment.

• Stroke is ischemic in origin, supratentorial, and radiologically confirmed (CT scan or diagnostic MRI) prior to enrolment.

• Patient is 24-48 hours from time of stroke onset when the first dose of NTxTM-265 therapy is administered. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when patient was last seen or was self-reported to be normal.

• Reasonable expectation of availability to receive the full 9 day NTxTM-265 course of therapy, and to be available for subsequent follow-up visits.

• Reasonable expectation that patient will receive standard post-stroke physical, occupational and speech therapy as indicated.

• Female patient is either:

1. Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral oophorectomy or hysterectomy) or

2. If of childbearing potential, agrees to use two of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits:

• Condoms, sponge, foams, jellies, diaphragm or intrauterine device, contraceptives (e.g., implants, injectables, combined oral, etc) OR

• A vasectomised partner OR

• Abstinence

Exclusion Criteria

• Patients presenting with lacunar, hemorrhagic and/or brain stem stroke.

• Patients who have received thrombolytic treatment with tPA following the index stroke.

• Patients classified as comatose, defined as a patient who required repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (NIHSS 1A score must be <2)

• Women who have 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.

• Serum hemoglobin > 16 g/dL (males) or > 14 g/dL (females); or platelet count > 400,000/mm3.

• Advanced liver,kidney, cardiac or pulmonary disease; the former will be operationally defined using NCI Toxicity Criteria (Grade 2 or higher)

• Serum bilirubin > 1.5 x upper limit of normal (ULN).

• Alkaline phosphatase > 2.5 x ULN.

• AST>2.5xULN.

• ALT > 2.5 x ULN.

• Creatinine > 2.0 x ULN.

• Patients with known and documented transferrin saturation < 20%.

• Patients with known and documented ferritin < 100 ng/mL.

• Patients with known and documented elevated PSA levels, or a PSA level of = 4 ng/mL at screening.

• Patients with a known or current history of abnormal hypercoagulability parameters , including known cardiolipin/antiphospholipid antibody syndrome.

• Expected survival < 1 year.

• Allergy or other contraindication to hCG including:

1. Prior hypersensitivity to hCG preparations or one of their excipients.

2. Primary ovarian failure.

3. Uncontrolled thyroid or adrenal dysfunction.

4. An uncontrolled organic intracranial lesion such as a pituitary tumor.

5. Abnormal uterine bleeding of undetermined origin.

6. Ovarian cyst or ovarian enlargement of undetermined origin.

7. Sex hormone dependent tumors of the reproductive organs, accessory sex glands, and breasts.

• Allergy or other contraindication to epoetin alfa:

1. Who developed pure red cell aplasia following treatment with any erythropoiesis regulating hormones

2. With uncontrolled hypertension

3. With known hypersensitivity to mammalian cell-derived products, albumin (human) or any component of the product

4. Who for any reason cannot receive adequate antithrombotic treatment

• A known diagnosis of cancer (except non-malignant skin cancer).

• Uncontrolled hypertension, defined in the context of acute stroke 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.

• Patients with a pre-stroke/pre-morbid modified Rankin Score (mRS) = 2.

• 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 or degree of stroke such that, in the investigator's opinion, the patient should not be included in the trial.

• With the exception of the qualifying stroke, any other stroke within the previous 6 months.

• Patients who cannot take anti-platelet therapy for the duration of the study.

• Patients who cannot take low molecular weight or unfractionated heparin during hospitalization.

• Pre-existing and active major psychiatric or other chronic neurological disease.

• Consume, on average, greater than 14 alcoholic drinks per week, or have a history of substance abuse or dependency within 12 months prior to the study.

• Currently participating in another investigational study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• NTx™-265: rhCG, then rEPO
rhCG 10,000 IU, SC, on Day 1, 3, and 5 of study participation, then rEPO 30,000 IU, IV, on Day 7, 8, and 9 of study participation
• Saline placebo
Saline SC, on Day 1, 3, and 5 of study participation, then Saline IV, on Day 7, 8, and 9 of study participation

Locations

Country	Name	City	State
Canada	Brandon Regional Health Centre	Brandon	Manitoba
Canada	Department of Clinical Neurosciences, Univeristy of Calgary	Calgary	Alberta
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Canada	Walter Mackenzie Health Sciences Centre	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	McMaster Clinic	Hamilton	Ontario
Canada	Chinook Regional Hospital	Lethbridge	Alberta
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	Montreal Neurological Institute	Montreal	Quebec
Canada	Penticton Regional Hospital	Penticton	British Columbia
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	Department of Neurology, St. Michael's Hospital	Toronto	Ontario
Canada	Division of Neurology , Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Vancouver Island Health Research Centre	Victoria	British Columbia
India	M S Ramaiah Memorial Hospital	Bangalore	Karnataka
India	Department of Neurology, Apollo Hospitals	Hyderabad	Andhra Pradesh
India	Department of Neurology, Care Hospital	Hyderabad	Andhra Pradesh
India	Department of Neurology, Nizam's Institute of Medical Science	Hyderabad	Andhra Pradesh
India	Krishna Institute of Medical Sciences	Hyderabad	Andhra Pradesh
India	AMRI Hospital	Kolkata	West Bengal
India	Department of Neurology, B.P.Poddar Hospital & Medical Research Ltd	Kolkata	West Bengal
India	Christian Medical College & Hospital	Ludhiana	Punjab
India	Max Super Speciality Hospital	New Delhi	Delhi
India	Department of Neurology, Christian Medical College	Vellore	Tamilnadu

Sponsors (1)

Lead Sponsor	Collaborator
Stem Cell Therapeutics Corp.

Countries where clinical trial is conducted

Canada,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Score (mRS)		Day 90	No
Primary	NIHSS response		Day 90	No
Secondary	NIHSS		Day 90	No
Secondary	mRS		Day 90	No
Secondary	Barthel Index		Day 90	No
Secondary	Action Research Arm Test		Day 90	No
Secondary	Gait Velocity Test		Day 90	No
Secondary	Boston Naming Test		Day 90	No
Secondary	Line Cancellation Test		Day 90	No
Secondary	Trails A & B Test		Day 90	No