Post-herpetic Neuralgia

Primary Objective(s)  To characterize dose-response for change in the weekly mean of 24-hour average pain intensity scores at Week 12 Secondary Objective(s)  To compare the efficacy of EMA401 vs. placebo in 24-hour average pain intensity score at Week 12, using an 11 point Numeric Rating Scale (NRS) by testing the superiority of at least one active dose of EMA401 vs. placebo  To evaluate the efficacy of EMA401 compared to placebo, as measured by the Brief Pain Inventory-Short Form (BPI-SF) interference total score at Week 12  To evaluate the efficacy of EMA401 compared to placebo, as measured by the weekly mean of the 24-hour worst pain intensity score, using an 11-point Numeric Rating Scale (NRS) at Week 12  To evaluate the efficacy of EMA401 compared to placebo, on the Patient Global Impression of Change (PGIC) at Week 12  To evaluate the proportion of EMA401 patients achieving a ≥ 30% and a ≥ 50% reduction in weekly mean 24-hour average pain intensity score using the NRS compared to placebo (i.e., responder rates) at Week 12  To evaluate the effect of EMA401 compared to placebo on the Insomnia Severity Index (ISI) at Week 12  To evaluate the effect of EMA401 compared to placebo on the Neuropathic Pain Symptom Inventory (NPSI) at Week 12  To evaluate the safety and tolerability of EMA401 compared to placebo in PHN patients, as measured by treatment emergent adverse events (TEAEs),adverse events (AEs) leading to study drug discontinuation and serious adverse events (SAEs) throughout the study  To evaluate the pharmacokinetics (PK) of EMA401 and exposure-response (decrease in pain intensity) relationship for EMA401 throughout the study

EMA401 (Olodanrigan)

EMA401 (Olodanrigan)

Capsule

12.5 mg, 50 mg, 150mg

Primary:
 Dose-response in change in weekly mean of the 24-hour average pain score, using an 11-point Numeric
Rating Scale (NRS), from Baseline to Week 12

Secondary:
 Change in weekly mean 24-hour average pain score (using the 11 point NRS) from Baseline to Week 12
 Change in BPI-SF interference total score from Baseline to Week 12
 Change in weekly mean of the 24-hour worst pain score, using an 11-point NRS, from Baseline to Week 12
 PGIC at Week 12
 Proportion of patients meeting responder criteria from Baseline to Week 12
 Change in ISI from Baseline to Week 12
 Change in NPSI from Baseline to Week 12
 Number and severity of treatment emergent adverse events and the frequency of adverse events leading to
discontinuation. Number of serious adverse events.
 Plasma pharmacokinetics of EMA401 will be characterized by population non-linear mixed effects modeling
techniques

1. Written informed consent must be obtained before any assessment is performed.
2. Males and females, 18 years and older.
3. At the time of Screening, have documented diagnosis of PHN (ICD-10 code B02.29),
defined as pain in the region of the rash persisting for more than 6 months after onset of
herpes zoster rash.
4a. Be assessed as suffering from moderate to severe neuropathic pain across the Screening
epoch (NRS ≥ 4). The assessment of moderate and severe pain will be made using a
proprietary screening algorithm (as described in Section 3.1). The designated investigator
site staff will be informed immediately as to whether the patient is eligible or ineligible on
the electronic tablet based on the patient entering all relevant pain scores in the eDiary
device.
5a. Patients must have documented past and/or ongoing inadequate treatment response
(having insufficient pain relief with treatment or inability to tolerate) to at least 2 different
prescribed therapies / analgesics commonly used to treat and considered effective for the
treatment of PHN.
6. Patient must be willing to complete daily eDiary

1. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days,
whichever is longer.
2. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar
chemical classes.
3a. Electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients
participating in the study such as:
 Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular
tachycardia, and clinically significant second or third degree Atrioventricular block
(AV block) without a pacemaker.
 History of familial long QT syndrome or known family history of Torsades de
Pointes.
4. Patients taking medications prohibited by the protocol (see Section 5.5.8,
Table 5-2).
5. Skin conditions in the affected dermatome that in the Investigator’s opinion could alter
sensation or active herpes zoster upon physical examination at Screening.
6a. History of malignancy of any organ system (other than localized basal cell carcinoma of
the skin or in situ cervical cancer), treated or untreated, within the past 2 years, regardless
of whether there is evidence of local recurrence or metastases.
7. Major depressive episode within 6 months prior to Screening and/or a history of
diagnosed recurrent major depressive disorder according to Diagnostic and Statistical
Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria (see Appendix 6).
8. Score “yes” on item 4 or item 5 of the Suicidal Ideation section of the Columbia Suicide
Severity Rating Scale (C-SSRS), if this ideation occurred in the past 6 months, or “yes” on
any item of the Suicidal Behavior section, except for the “Non-Suicidal Self-Injurious
Behavior” (item also included in the Suicidal Behavior section), if this behavior occurred
in the past 2 years.
9. Pregnant or nursing (lactating) women.
10a. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant unless they are using highly effective methods of contraception during
dosing and for 3 days after stopping of study medication. Highly effective contraception
methods include:
 Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
 Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking
investigational drug. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment.
 Male sterilization (at least 6 months prior to screening). For female subjects on the
study, the vasectomized male partner should be the sole partner for that subject.
 Placement of an intrauterine device (IUD) or intrauterine system (IUS).
In case local regulations deviate from the contraception methods listed above, local regulations
apply and will be described in the Informed Consent Form (ICF)
Women are considered post-menopausal and not of child bearing potential if they have had 12
months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age
appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy
(with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In
the case of oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment is she considered not of child bearing
potential.
11. This criterion has been removed in this amendment.
12. Have evidence of significant renal insufficiency, indicated by an estimated glomerular
filtration rate (eGFR) using the modification of diet in renal disease (MDRD) equation of
< 40 mL/min/1.73 m2
at Screening (as calculated by the central laboratory).
13. Alcohol Use Disorder or other Substance-use disorders (other than nicotine or caffeine) in
accordance with DSM-V criteria within 12 months of screening (see Appendix 7).
14a. Positive urine drug screen at Screening. (See section 6.5.4.5).
15a. Evidence of pre-existing liver condition as defined as any of the following:
 Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 1.5 X ULN
(upper limit of normal), or total bilirubin or alkaline phosphatase >ULN for the
central laboratory at Screening.
 Known history of or active hepatitis B virus (HBV), hepatitis C virus (HCV), or
human immunodeficiency virus (HIV).
 Hepatitis A or B vaccination within 3 months of Screening.
 Active gallbladder or bile duct disease.
 Acute or chronic pancreatitis.
16. Have platelets ≤ 100 x 109
/L, or neutrophil count < 1.2 x 109
/L (or equivalent), or
hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men.
17. Patients who have a known diagnosis of diabetes and are stable on medication with a
hemoglobin A1c > 8%. Those who do not have a known diagnosis of diabetes with a
hemoglobin A1c > 7%.
18a. Other conditions :
 Have an active, uncontrolled medical condition (e.g., neurological, gastrointestinal,
renal, hepatic, cardiovascular, pulmonary, metabolic, endocrine, hematological,
genitourinary or other major disorder), psychotic disorder or any other uncontrolled
psychiatric illness (patients who are not stable on medication for at least two months
prior are excluded), or any other significant clinical disorder or laboratory finding.
 Had a clinically significant illness or operative procedure within four weeks of
Screening (e.g., influenza, myocardial infarction).
 Have, any other pain in the region of the herpes zoster rash or any other moderate to
severe pain that can be confused with the patient’s PHN, or other chronic pain
conditions including osteoarthritis, that may confound evaluation of treatment
response.
19. Have undergone neurolytic or neurosurgical therapy or use a neuro stimulating device for
PHN within 3 months of Screening or are using/ plan to use Transcutaneous Electrical
Nerve Stimulation (TENS).
20a. Subjects with an ongoing litigation related to their pain disorder.
21. This criterion has been removed in this amendment
22. This criterion has been removed in this amendment.