Gene Transfer for Cancer Pain

Cancer Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00804076
• Other study ID #: NP2/P1/07/1
• Status: Completed
• Phase: Phase 1
• First received: December 3, 2008
• Last updated: February 18, 2014
• Start date: February 2008
• Est. completion date: July 2013

Study information

• Verified date: February 2014
• Source: Diamyd Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 2013
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer Pain

Intervention

Biological:
• NP2
Intradermal injection of NP2 at doses ranging from 10e7 to 10e9 pfu at the site of pain.

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Pain Research of Oregon, LLC	Eugene	Oregon
United States	Advanced Pharma CR	Miami	Florida
United States	Louisiana Research Associates	New Orleans	Louisiana
United States	Center for Clinical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Diamyd Inc

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety measured by vital signs, physical exam findings, clinical laboratory analyses and treatment related Adverse Events (AE).		4 Months	Yes
Secondary	Evaluate changes in cancer-related pain		4 Months	No