Gene Transfer for Cancer Pain

Gene Transfer for Intractable Pain: A Phase I Clinical Trial to Determine the Maximum Tolerable Dose of a Replication-Defective Herpes Simplex Virus Type I (HSV-1) Vector Expressing Human Preproenkephalin (NP2) in Patients With Malignancies

The primary purpose of this study is to examine the safety of NP2 (a nonreplicating HSV-based vector expressing enkephalin) in patients with cancer pain. The secondary purpose is to evaluate efficacy.

Study Overview

• Status: Completed
• Conditions: Cancer Pain
• Intervention / Treatment: Biological: NP2

Detailed Description

Therapeutic HSV-based vectors deliver genes from skin inoculation to sensory neurons to interrupt pain signaling at the spinal level. Side effects may be limited by the focal distribution of vector delivery and preproenkephalin expression. Preproenkephalin is a natural human gene that produces peptides that bind to opioid receptors in the body. The therapeutic being evaluated, NP2, is a replication defective herpes simplex type 1 virus (HSV-1) modified to express the human preproenkephalin gene that has demonstrated efficacy in numerous model of pain, including pain caused by cancer.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33175
      • Advanced Pharma Cr
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates
  • Michigan
    • Ann Arbor, Michigan, United States, 49109
      • University of Michigan Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Center for Clinical Research
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pain Research of Oregon, LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with intractable pain from malignant disease with a 5 year projected survival of less than 25%.
2. Female patients of childbearing potential who have a negative pregnancy test and using birth control.
3. Patients who have not received recent treatment with a radiation, chemotherapeutic or immunotherapeutic agent and are not expected to undergo such treatment 28 days after injection of NP2.
4. Patients who have not had surgical stabilization/resection within 4 weeks of Screening and have no plans for additional surgical procedures.
5. Patients with adequate bone marrow function, IgG levels greater than 565 mg% and CD4 count greater than 500. .

Exclusion Criteria:

1. Patients with serious uncontrolled medical conditions other than malignancy.
2. Patients with severe liver or renal impairment
3. Patients currently or previously with positive serology for HIV, Hepatitis B or Hepatitis C.
4. Patients with a hemoglobin <9 gm% or uncontrolled coagulopathy or bleeding diathesis.
5. Patients with a clinical diagnosis of any active herpes infection within the past 6 months.
6. Patients who have been vaccinated to prevent HSV infection or a history of shingles or the presence of active shingles.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NP2; Intradermal injection	Biological: NP2; Intradermal injection of NP2 at doses ranging from 10e7 to 10e9 pfu at the site of pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety measured by vital signs, physical exam findings, clinical laboratory analyses and treatment related Adverse Events (AE).	4 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate changes in cancer-related pain	4 Months

Collaborators and Investigators

• Sponsor: Diamyd Inc
• Investigators: Principal Investigator: David J Fink, MD, University of Michigan Department of Neurology

Publications and helpful links

General Publications

• Goss JR, Mata M, Goins WF, Wu HH, Glorioso JC, Fink DJ. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther. 2001 Apr;8(7):551-6. doi: 10.1038/sj.gt.3301430.
• Hao S, Mata M, Goins W, Glorioso JC, Fink DJ. Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain. Pain. 2003 Mar;102(1-2):135-42. doi: 10.1016/s0304-3959(02)00346-9.
• Goss JR, Harley CF, Mata M, O'Malley ME, Goins WF, Hu X, Glorioso JC, Fink DJ. Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann Neurol. 2002 Nov;52(5):662-5. doi: 10.1002/ana.10343.
• Glorioso JC, Fink DJ. Herpes vector-mediated gene transfer in the treatment of chronic pain. Mol Ther. 2009 Jan;17(1):13-8. doi: 10.1038/mt.2008.213. Epub 2008 Oct 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: December 3, 2008
• First Submitted That Met QC Criteria: December 5, 2008
• First Posted (Estimate): December 8, 2008

Study Record Updates

• Last Update Posted (Estimate): February 19, 2014
• Last Update Submitted That Met QC Criteria: February 18, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: pain; gene therapy; intradermal; replication defective HSV vector; enkephalin
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain
• Other Study ID Numbers: NP2/P1/07/1