3VM1001 Cream for the Treatment of Pain Associated With Post Herpetic Neuralgia (PHN)

Post-herpetic neuralgia (PHN) is defined as pain following acute herpes zoster (AHZ) lasting
>3 months. PHN develops in about 10% of patients following an episode of AHZ. 95% of adults
ate seropositive for varicella zoster virus antibodies, and are, therefore, at risk for AHZ
and PHN. Wider use of AHZ vaccine approved in 2006 may reduce the incidence of PHN.
Nevertheless, PHN may be severe and frequently interferes with daily activities and with
sleep.

First line management of PHN pain currently is tricyclic anti-depressants and
anti-convulsants such as gabapentin and pregabalin, and use of a 5% lidocaine patch. second
line therapies include opioid analgesia and topical capsaicin: combinations of topical and
systemic therapies may be used as well. These therapies have common side effects of dry
mouth, constipation, sedation, urinary retention, nausea, somnolence, dizziness, weight gain
and peripheral edema.

there is an unmet medial need for topical therapies that demonstrate efficacy without the
significant side effects o the therapies mentioned above. 3VM cream, a low concentration of
copper in a cream vehicle may b such a therapy.

Inclusion Criteria:

- Diagnosis of PHN for >3 months;

- Persistent pain for more than 6 months from appearance of herpes zoster rash that is
not located above the scalp hairline, or in immediate proximity to mucous membranes
(given the low toxicity of copper, PHN affecting the face and neck will be included,
but subjects will be trained on avoidance of contact with the eyes or mouth);

- Age 18 years or older;

- Males or females of non-childbearing potential (i.e., 12 months or more of spontaneous
amenorrhea, bilateral oophorectomy at least 6 months prior to randomization,
hysterectomy with bilateral oophorectomy at least 6 months prior to randomization, or
for females over 50 years of age, hysterectomy without bilateral oophorectomy at least
6 months prior to randomization); female subjects of childbearing potential must agree
to use contraception (abstinence, birth control pills, rings or patches, diaphragm and
spermicide, intrauterine device, condom and vaginal spermicide, surgical
sterilization, vasectomy, progestin implant or injection); female partners of
childbearing potential of male subjects must agree to use contraception as defined
above;

- Persistent neuropathic pain that involves at least 1 dermatome and covering no more
than 400 cm2 (the target area);

- Pain intensity in the target area of > 40mm on a 100mm VAS at screening;

- Intact skin over the target area to be treated;

- Subject agrees to take only the protocol-defined rescue medication as prescribed;

- All concurrent medications taken for any reason except for the treatment of PHN must
be stable (dose, frequency) for 14 days;

- Ability to follow protocol with reference to cognitive and situational factors (eg.
stable housing, ability to attend visits);

- Ability to read and write English;

- Ability to apply cream without assistance;

- Able to provide written informed consent.

Exclusion Criteria:

- Subject with systemic disease that would put him/her at an additional risk or limit
his/her ability to participate in the study in the opinion of the investigator;

- Subject with known history of human immunodeficiency virus, hepatitis C, or hepatitis
B;

- Malignancy other than basal cell carcinoma and carcinoma in situ within the past 2
years;

- Subject who has an active history of alcohol or drug abuse;

- Wilson's disease or other known disorder of copper metabolism;

- Known hypersensitivity or allergy to any component of the product, or to acetaminophen

- Pregnant and breastfeeding women.

- Subject with active herpes zoster lesions;

- Subject with open skin lesions or skin infections in the target area, or conditions
over the target area such as eczema or psoriasis;

- Mild pain in the target area, characterized by VAS score of < 40 mm

- Pain in any other part of the body that could interfere with the patient's assessment
of pain in the target area

- Subject who has taken concomitant medications for the treatment of PHN (except
acetaminophen or gabapentin) in the last four weeks. If taking gabapentin the dose
must have been stable for at least four weeks;

- Treatment with local anesthetic or steroids (including lidocaine patch, transcutaneous
electrical nerve stimulation, etc.) in the last 2 weeks or nerve blocks within the
last 30 days;

- Subject who has used capsaicin preparations on a regular basis in the 90 days prior to
screening and at all in the past two weeks;

- Use of prohibited concomitant medications/therapies;

1. Devices or therapeutic treatments for pain apart from acetaminophen as a rescue
medication

2. Systemic corticosteroids

3. Other Investigational Drugs

4. Chemotherapeutic drugs

5. Immunotherapy

6. Topical products applied to the target skin area

- Subject with history of serious mental illness or psychiatric illness such as
dementia, depression, or schizophrenia, that will limit his/her ability to comply with
study procedures;

- Subject who is unable to apply, or have a care giver apply, study ointment to the area
of most painful skin segments, three times daily, once within 2 hours of waking, once
mid-afternoon, and once prior to bedtime;

- Subject who has participated in any other investigational study within 60 days prior
to screening;

- Subject who is employed by the Sponsor, study staff, and their families; or

- Subject who has any condition that would make him/her, in the opinion of the
investigator or Sponsor, unsuitable for the study.