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

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

The purpose of this study is:

• To assess the neurological outcome in acute ischemic stroke patients treated with NTx®-265, when compared with patients given a placebo control.
• To assess the safety and tolerability of NTx®-265 when given to acute ischemic stroke patients.

Study Overview

• Status: Terminated
• Conditions: Stroke
• Intervention / Treatment: Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); Drug: Saline Placebo

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Center , University of Calgary
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute
• India
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Lalitha Super Specialty Hospitals Pvt.Ltd
    • Hyderabad, Andhra Pradesh, India, 500001
      • Care Hospital
    • Hyderabad, Andhra Pradesh, India, 500003
      • Krishna Institute of Medical Sciences
    • Hyderabad, Andhra Pradesh, India, 500018
      • St.Theresa's General Hospital
    • Hyderabad, Andhra Pradesh, India, 500023
      • Apollo Hospitals
    • Hyderabad, Andhra Pradesh, India, 500059
      • Owaisi Hospital and Research Centre
    • Hyderabad, Andhra Pradesh, India, 500063
      • Mediciti Hospital
    • Hyderabad, Andhra Pradesh, India, 500068
      • Kamineni Hospital
    • Tirupati, Andhra Pradesh, India, 517501
      • DBR & SK Super Speciality Hospital
    • Vijayawada, Andhra Pradesh, India, 520002
      • Latha Superspecialities Hospital
    • Vijayawada, Andhra Pradesh, India, 520002
      • Suraksha Neuro Centre
  • Delhi
    • New Delhi, Delhi, India, 110017
      • Max Super Speciality Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • M S Ramaiah Memorial Hospital
    • Bangalore, Karnataka, India, 570004
      • J.S.S Medical College & Hospital
  • Kerala
    • Thiruvananthapuram, Kerala, India, 695024
      • Ananthapuri Hospitals and Research Institute
  • Punjab
    • Ludhiana, Punjab, India, 141008
      • Christian Medical College and Hospital
  • Tamilnadu
    • Chennai, Tamilnadu, India, 600026
      • Vijaya Health Center
    • Vellore, Tamilnadu, India, 632004
      • Christian Medical College Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-85
• NIHSS score 8-20
• Stroke is ischemic in origin, supratentorial, and radiologically confirmed
• Patient is 24-48 hours from time of stroke onset when the first dose of NTx®-265 therapy is administered
• Reasonable expectation of availability to receive the full 9 day NTx®- 265 therapy and subsequent follow-up visits
• Reasonable expectation that patient will receive standard post-stroke physical, occupational, speech, and cognitive therapy as indicated
• Female patient is either not of childbearing potential or agrees to use two of the effective separate non-hormonal forms of contraception throughout the study

Exclusion Criteria:

• Patients presenting with lacunar, hemorrhagic and/or brain stem stroke
• Patients who have received tissue plasminogen activator (tPA)following the index stroke
• Patients classified as comatose
• Women who have tested positive for pregnancy, or are breast-feeding, or are not using a birth control
• Serum hemoglobin > 16 grams(g)/deciliter (dL)(males) or > 14 g/dL (females); or platelet count > 400,000/cubic millimeters(mm3)
• Advanced liver, kidney, cardiac, or pulmonary disease
• Elevated serum bilirubin,alkaline phosphatase, aspartate aminotransferase (AST) or alanine transaminase (ALT),creatinine, or prostate-specific antigen (PSA) levels
• Patients with a known history of hypercoagulability
• Expected survival < 1 year
• Allergy or other contraindication to hCG or EPO
• A known diagnosis of cancer in the previous 5 years
• Uncontrolled hypertension
• Use of either hCG or epoetin alfa within the previous 90 days
• Any condition known to elevate hCG
• Patients with a pre-stroke/pre-morbid modified Rankin Score (mRS)≥ 2
• Any patients not living independently
• 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 3 months
• Patients who cannot take anti-platelet or anti-coagulant therapy
• Pre-existing and active major psychiatric or other chronic neurological disease
• Alcohol abuse or have a history of substance abuse or dependency within 12 months prior to the study
• Currently participating in another investigational study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NTx®-265 Low Dose; hCG 385 µg (10,000 international unit [IU]), subcutaneously (SC), on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, intravenously (IV), on Day 7, 8, and 9 of study participation	Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 12,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 20,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle
Experimental: NTx®-265 Medium Dose; hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 12,000 IU, IV, on Day 7, 8, and 9 of study participation	Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 12,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 20,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle
Experimental: NTx®-265 High Dose; hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 20,000 IU, IV, on Day 7, 8, and 9 of study participation	Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 12,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle; Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO); hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 20,000 IU, IV, on Day 7, 8, and 9 of study participation; Other Names: Epogen; Eprex; Ovidrel; Ovitrelle
Placebo Comparator: Saline Placebo	Drug: 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; Other Names: Sodium Chloride 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90	The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead).	Baseline and Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIHSS Response >=4 at Day 90	The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead). NIHSS Response >=4 is defined as a >=4 change from baseline at Day 90.	Baseline and Day 90
NIHSS Change From Baseline at Day 30	The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead).	Baseline and Day 30
Modified Rankin Scale (mRS) Response <=2 at Day 90	The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0 (perfect health without symptoms) to 6 (dead). mRS response <=2 is defined as the mRS score <=2 at Day 90.	Day 90
Barthel Index at Day 90	The Barthel Index measures 10 activities of daily living and mobility. A score of 100 = is best (able to live at home with a degree of independence), 0 is worst.	Day 90
Action Research Arm Test (ARAT) Change From Baseline at Day 90	The ARAT assesses recovery of arm function following stroke through a series of subtests judging ability to grasp, grip, pinch, or move the arm; scores are on a scale; The total maximum (best) score is 57 and the total minimum (worst) score is 0.	Baseline and Day 90
Gait Velocity Test Change From Baseline at Day 90	The Gait Velocity Test assesses ability to walk as measured by the time (seconds) it takes a patient to walk 10 meters.	Baseline and Day 90
Boston Naming Test (BNT) Change From Baseline at Day 90	The BNT assesses impairment of language ability by asking patients to identify 20 different pictures each time the test is taken. A score of 20 is best, 0 is worst.	Baseline and Day 90
Line Cancellation Test Change From Baseline at Day 90	The Line Cancellation Test detects the loss of awareness of one side of the body. A score of 0.00 (no units) is normal (patient favors neither right nor left side). A score of +1.00 indicates severe unawareness of the left side. A score of -1.00 indicates severe unawareness of the right side.	Baseline and Day 90
Trails A Test Change From Baseline at Day 90	The Trails A test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 numbers (e.g., 1, 2, 3, 4…)	Baseline and Day 90
Trails B Test Change From Baseline at Day 90	The Trails B test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 alpha numeric circles (e.g., 1, A, 2, B, 3, C, 4, D)	Baseline and Day 90
Geriatric Depression Scale at Day 90	The Geriatric Depression Scale is commonly used to assess depression in stroke patients of any age by asking 15 yes/no questions, and then scored. A score of 0 - 5 is normal, whereas a score of 6 -15 suggests depression.	Day 90

Collaborators and Investigators

• Sponsor: Stem Cell Therapeutics Corp.
• Investigators: Principal Investigator: Steven C Cramer, MD, Department of Neurology, University of California, Irvine Medical Center; Principal Investigator: Michael D Hill, MD, Department of Clinical Neurosciences, University of Calgary

Publications and helpful links

General Publications

• Cramer SC, Hill MD; REGENESIS-LED Investigators. Human choriogonadotropin and epoetin alfa in acute ischemic stroke patients (REGENESIS-LED trial). Int J Stroke. 2014 Apr;9(3):321-7. doi: 10.1111/ijs.12260. Epub 2014 Mar 3.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: July 9, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): November 29, 2011
• Last Update Submitted That Met QC Criteria: November 24, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Reproductive Control Agents; Hematinics; Epoetin Alfa; Chorionic Gonadotropin
• Other Study ID Numbers: NTx®-265-CP-202-IS