Gene Transfer for Cancer Pain

Tracking Information
First Submitted Date ICMJE	December 3, 2008
First Posted Date ICMJE	December 8, 2008
Last Update Posted Date	February 19, 2014
Study Start Date ICMJE	February 2008
Actual Primary Completion Date	November 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 5, 2008)	Safety measured by vital signs, physical exam findings, clinical laboratory analyses and treatment related Adverse Events (AE). [ Time Frame: 4 Months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00804076 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 5, 2008)	Evaluate changes in cancer-related pain [ Time Frame: 4 Months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Gene Transfer for Cancer Pain
Official Title ICMJE	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
Brief Summary	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.
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 ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Cancer Pain
Intervention ICMJE	Biological: NP2; Intradermal injection of NP2 at doses ranging from 10e7 to 10e9 pfu at the site of pain.
Study Arms	Experimental: NP2; Intradermal injection; Intervention: Biological: NP2
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.; 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.; 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.; 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. Review.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 18, 2014)	10
Original Estimated Enrollment ICMJE; (submitted: December 5, 2008)	12
Actual Study Completion Date	July 2013
Actual Primary Completion Date	November 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients with intractable pain from malignant disease with a 5 year projected survival of less than 25%.; Female patients of childbearing potential who have a negative pregnancy test and using birth control.; 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.; Patients who have not had surgical stabilization/resection within 4 weeks of Screening and have no plans for additional surgical procedures.; Patients with adequate bone marrow function, IgG levels greater than 565 mg% and CD4 count greater than 500. . Exclusion Criteria: Patients with serious uncontrolled medical conditions other than malignancy.; Patients with severe liver or renal impairment; Patients currently or previously with positive serology for HIV, Hepatitis B or Hepatitis C.; Patients with a hemoglobin <9 gm% or uncontrolled coagulopathy or bleeding diathesis.; Patients with a clinical diagnosis of any active herpes infection within the past 6 months.; Patients who have been vaccinated to prevent HSV infection or a history of shingles or the presence of active shingles.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00804076
Other Study ID Numbers ICMJE	NP2/P1/07/1
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Diamyd Inc
Study Sponsor ICMJE	Diamyd Inc
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: David J Fink, MD University of Michigan Department of Neurology
PRS Account	Diamyd Inc
Verification Date	February 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP