Trial of Oral Valproic Acid for Retinitis Pigmentosa

Retinitis Pigmentosa (RP) is an incurable and untreatable group of heterogeneous retinal
degenerative diseases that cause severe visual loss. There is currently no therapeutic that
substantially slows the progression of this disease, and certainly none that can restore
vision in RP patients. The Valproic Acid (VPA) study is designed as a six-site,
interventional, prospective, randomized, placebo controlled, double-blinded study of 90
participants to evaluate the efficacy of oral Valproic Acid to both slow the progression of
visual function loss and/or to restore visual function in patients with an Autosomal Dominant
RP genetic mutation and to collect safety and tolerability information. Patients that
participate in the study will be randomized to either placebo or VPA in a 1:1 ratio.

Inclusion Criteria:

1. Understand/sign the IRB-approved study informed consent document.

2. Age greater than or equal to 18 years, no upper age limit

3. Males and non-child bearing females must weigh ≥40 Kg and ≤158.9 Kg; Females of child
bearing potential must weigh ≥40 Kg and ≤74.9 Kg.

4. Diagnosis of Retinitis Pigmentosa (RP).

5. Visual acuity of greater than or equal to 35 letters in at least one eye as measured
by the EVA-ETDRS (equivalent to 20/200 on a Snellen chart).

6. Genotyped as autosomal dominant form of RP.

7. Female subjects of childbearing potential and male subjects able to father children
must have (or have a partner who has) had a hysterectomy or vasectomy, be completely
abstinent from intercourse or must commit to practice at least two acceptable methods
of contraception to minimize the chance of pregnancy during the study and for the 13
week period after stopping the study drug.

8. Female subjects of childbearing potential must have a negative urine pregnancy test at
study entry and throughout the duration of the study.

9. Willingness to comply with the protocol.

Exclusion Criteria:

1. Medical problems that make consistent follow-up over the treatment period unlikely
(e.g. stroke, severe MI, end stage malignancy), or in general a poor medical risk
because of other systemic diseases or active uncontrolled infections.

2. Other retinal diseases: Glaucoma, retinal inflammatory disease (CME is allowable),
cataract worse than +2 NS, or herpes simplex virus of the eye.

3. Intact visual field of 5⁰ or less.

4. Subject unable to provide reliable perimetry measurements in both eyes for both static
and kinetic visual field, as determined by the Reading Center.

5. Diabetes.

6. History of cancer (other than non-melanoma skin cancer) diagnosed, or requiring
treatment within the past 2 years.

7. A hemoglobin concentration, a platelet count or an absolute neutrophil count below the
lower limit of normal at study entry.

8. Suspected liver dysfunction determined by having liver function values elevated above
the upper limit of normal.

9. History of pancreatitis by clinical features and/or laboratory abnormalities in the
last 12 months.

10. Renal dysfunction based on serum creatinine,(MDRD) equation.

11. Urea cycle disorders.

12. History of neurological conditions including epilepsy, history of brain injury,
encephalitis, or any organic brain syndrome.

13. History of schizophrenia, schizoaffective disorder, bipolar disorder, suicidality or
organic mental disorders.

14. Currently receiving valproic acid or other anti-convulsants.

15. Sensitive to or have ever had an allergic reaction to valproic Acid.

16. Sensitive to or have ever had an allergic reaction to peanuts as peanut oil is an
inactive ingredient in valproic acid capsules and the placebo.

17. Has taken one of the disallowed drugs at least 2 weeks prior to randomization.

18. Pregnant women.

19. Lactating mothers who are breast feeding their babies.

20. RP patients involved in other clinical trials within the last 3 months.

21. Require enrollment by consent of a legally authorized representative.

22. Persons who are unable to read are not allowed to consent for themselves or others to
participate in this study.

23. The potential participant lives in the same household as a current participant in this
protocol.