Clinical trial NCT00804076: Gene Transfer for Cancer Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer Pain
Keywords: gene therapy
replication defective HSV vector
pain
enkephalin
intradermal
Lead sponsor: Diamyd Inc
Sponsor class: INDUSTRY
First posted: 2008-12-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety measured by vital signs, physical exam findings, clinical laboratory analyses and treatment related Adverse Events (AE).
timeFrame: 4 Months
Secondary outcomes:
measure: Evaluate changes in cancer-related pain
timeFrame: 4 Months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Advanced Pharma CR
state: Florida
city: New Orleans
country: United States
facility: Louisiana Research Associates
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Winston-Salem
country: United States
facility: Center for Clinical Research
state: North Carolina
city: Eugene
country: United States
facility: Pain Research of Oregon, LLC
state: Oregon
Study officials:
affiliation: University of Michigan Department of Neurology
name: David J Fink, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.