Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Painful Diabetic Neuropathy Clinical Trial

Official title:

A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of VM202 in Participants With Painful Diabetic Peripheral Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02427464
• Other study ID #: VMDN-003
• Status: Completed
• Phase: Phase 3
• Start date: April 2016
• Est. completion date: April 2019

Study information

• Verified date: July 2022
• Source: Helixmith Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of bilateral intramuscular injections of VM202 versus placebo in the treatment of painful diabetic peripheral neuropathy.

A total of 507 of 477 planned participants were randomized in a 2:1 ratio to one of two treatment groups. Note that 500 participants received IP treatment, whereas 7 participants did not receive IP treatment.

Treatments - Engensis (VM202) - 336 Engensis of 318 planned participants

Control - Placebo (VM202 vehicle) - 164 Placebo of 159 planned participants

Randomization were stratified by current use of gabapentin and/or pregabalin.

Description:

Peripheral neuropathy is a serious complication of diabetes. This form of neuropathy carries a high risk of pain, trophic changes, and autonomic dysfunction. Current treatments of diabetic peripheral neuropathy (DPN) are based on either pathogenetic mechanisms or symptomatic relief. A number of clinical trials have established symptomatic treatment but for pathogenetic mechanisms, the only proven treatment strategy is strict glycemic control. Clearly, it would be desirable to prevent, impede, or reverse the disrupting and often life-threatening manifestations of peripheral neuropathy by stimulating growth or regeneration of peripheral nerve axons.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age = 18 years to = 75 years

2. Documented history of type I or II diabetes with current treatment control (HbA1c of = 10.0% at Screening) and currently on medication for diabetes (oral, injectable, and/or insulin)

3. No significant changes anticipated in diabetes medication regimen

4. No new symptoms associated with diabetes within the last 3 months prior to study entry

5. Diagnosis of painful diabetic peripheral neuropathy in both lower extremities

6. Lower extremity pain for at least 6 months

7. Visual analog scale (VAS) score of = 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)

8. Symptoms from the Brief Pain Neuropathy Screening (BPNS) is = 5 point difference between legs at Initial Screening

9. The average daily pain intensity score of the Daily Pain and Sleep Interference Diary completed after medication wash-out is = 4 with a standard deviation = 2

10. The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is = 3 at Screening

11. Subjects on gabapentin (Neurontin), pregabalin (Lyrica), duloxetine (Cymbalta) for painful DPN at study entry must be on stable regimen of these treatments for at least 3 months prior to study entry

12. If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study

Exclusion Criteria:

1. Peripheral neuropathy caused by condition other than diabetes

2. Other pain more severe than neuropathic pain that would prevent assessment of DPN

3. Progressive or degenerative neurological disorder

4. Myopathy

5. Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)

6. Active infection

7. Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)

8. Positive HIV or HTLV at Screening

9. Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAb), antibody to Hepatitis B surface antigen (IgG and IgM; HBsAb), Hepatitis B surface antigen (HBsAg), and Hepatitis C antibodies (Anti HCV) at Screening

10. Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy, or radiation therapy

11. Stroke or myocardial infarction within last 3 months

12. Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, Creatinine > 2.0 mg/dL; AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary

13. Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination

14. Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at Screening

15. Subjects with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence for one year); subjects with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings

16. Use of the following drugs / therapeutics is prohibited. Subjects may participate in the study if they are willing to discontinue use of these drugs / therapeutics 7 days prior to starting the 7 Day Daily Pain and Sleep Interference Diary. Subjects must refrain from taking these drugs or undergoing these therapies for the duration of the study

• skeletal muscle relaxants, opioids, benzodiazepines (except for stable bedtime dose),

• capsaicin, local anesthetic creams (except for lidocaine cream prior to IM injection) and patches, isosorbide dinitrate (ISDN) spray,

• transcutaneous electrical nerve stimulation (TENS), acupuncture

17. If not using gabapentin (Neurontin) or pregabalin (Lyrica), subjects must agree not to start these drugs for the first 180 days of the study. Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study;

18. If not using duloxetine (Cymbalta), any antidepressants (e.g., amitriptyline and venlafaxine), any other antiepileptics (e.g., valproic acid, carbamazepine, vigabatrin), subjects must agree not to start these drugs for the first 6 months of the study.

Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study

19. Subjects requiring > 81 mg daily of acetylsalicylic acid; subjects may be enrolled if willing/able to switch to = 81 mg daily of acetylsalicylic acid or to another medication

20. Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (except inhaled steroids or ocular steroids) subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs until Day 180 of the study

21. Major psychiatric disorder within the last 180 days that would interfere with study participation

22. Body mass index (BMI) > 45 kg/m2 at Screening

23. Any lower extremity amputation due to diabetic complications

24. Use of an investigational drug or treatment in past 6 months, or prior participation in any study of Engensis (VM202)

25. Unable or unwilling to give informed consent

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Neuropathy, Painful
• Pain
• Painful Diabetic Neuropathy
• Peripheral Nervous System Diseases

Intervention

Biological:
• Engensis (VM202)
gene therapy

Other:
• placebo

Locations

Country	Name	City	State
United States	The Brigham and Women's Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Innovative Research of West Florida	Clearwater	Florida
United States	Western Washington Medical Group	Everett	Washington
United States	Associated Neurologists of Southern Connecticut, PC	Fairfield	Connecticut
United States	University of Florida McKnight Brain Institute	Gainesville	Florida
United States	Nerve and Muscle Center of Texas	Houston	Texas
United States	UF Health College of Med, Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Richard S. Cherlin, MD	Los Gatos	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center Department of Neurology	New York	New York
United States	EVMS (Eastern Virginia Medical School)	Norfolk	Virginia
United States	Compass Research, LLC	Orlando	Florida
United States	Arizona Research Center	Phoenix	Arizona
United States	Raleigh Neurology Associates, P.A.	Raleigh	North Carolina
United States	Rainier Clinical Research Center, Inc.	Renton	Washington
United States	Northern California Research	Sacramento	California
United States	University of Utah -Neurology	Salt Lake City	Utah
United States	Center for Clinical Research	San Francisco	California
United States	Neurological Research Institute	Santa Monica	California
United States	Clinical Research of West Florida	Tampa	Florida
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Martin Foot and Ankle	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Helixmith Co., Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kessler JA, Shaibani A, Sang CN, Christiansen M, Kudrow D, Vinik A, Shin N; VM202 study group. Gene therapy for diabetic peripheral neuropathy: A randomized, placebo-controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth facto — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Average 24 Hour Pain Score From Baseline to Day 90	Participants rated their 24-hour average daily pain intensity score using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in a Daily Pain and Sleep Interference Diary	The Pain and Sleep Interference diary was completed by participants for at least 5 assessments during a 7-day period at Screening (the mean 24-hour score was the reference/baseline score) and within 14 days prior to Day 90 visit.
Primary	Participants With at Least at 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 90	Number of participants with at least a 50 percent reduction in average 24-hour pain score, using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in the Daily Pain and Sleep Interference Diary	Baseline to Day 90
Primary	Number of Participants With Treatment-emergent Adverse Events.	Number of Participants with at least one treatment-emergent adverse events.	Baseline to Day 270
Secondary	Change in the Average 24-hour Pain Score From Baseline to Day 180	Participants rated their 24-hour average daily pain intensity score using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in the Daily Pain and Sleep Interference Diary	Baseline to Day 180
Secondary	Participants With at Least a 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 180	The number of participants with at least a 50% reduction in average 24-hour pain score using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in the Daily Pain and Sleep Interference Diary	Baseline to Day 180

External Links

•   Clin Transl Sci. 2021;00:1-9