Clinical trial NCT03094195: Dose Response Study of EMA401 in Patients With Post-herpetic Neuralgia (PHN)
Official title: A Double-blind, Placebo-controlled, Randomized Dose Ranging Trial to Determine the Safety and Efficacy of Three Dose Levels of EMA401 in Reducing 24-hour Average Pain Intensity Score in Patients With Post-herpetic Neuralgia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Post-herpetic Neuralgia
Keywords: post-herpetic neuralgia
neuropathic pain
angiotensin II type 2 receptor antagonist
dose ranging
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-03-29
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to characterize dose response, and evaluate safety and efficacy of three different doses of EMA401 compared to placebo in patients with post-herpetic neuralgia (PHN).

Detailed description: This was an interventional, randomized, parallel, placebo-controlled, dose ranging, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. The study was planned in two cohorts. The initial cohort had three treatment arms i.e. Placebo b.i.d., EMA401 25 mg b.i.d., or EMA401 100 mg b.i.d. Following an unblinded safety review by an independent DMC, the second cohort was to have been initiated with an additional treatment arm i.e. EMA401 300 mg b.i.d.. Due to the premature study termination, the second cohort was not initiated. At the end of treatment period the 25mg BID and 100mg BID arms were re-randomized (1:1) to the same treatment or placebo. Placebo arm stayed on placebo. The planned duration of treatment period was 12 weeks and 1 week of treatment withdrawal at the end of treatment period. The study was terminated early due to pre-clinical toxicity data that became available after start of trial. Novartis implemented a Urgent Safety Measure (USM) which instructed sites to discontinue study treatment immediately and to have all patients return for additional laboratory assessments (full hematology including coagulation and clinical chemistry panel). Safety data from the USM was presented as a separate outcome measure table and not included in the Adverse Event section.

Eligibility criteria: Inclusion Criteria:

* At the time of Screening, must have had 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.
* Assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS ≥ 4).
* Patients must have had 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 commonly used to treat and considered effective by the Investigator for the treatment of PHN.
* Patient must have been willing to complete daily eDiary

Exclusion Criteria:

* History or had current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study
* Had a 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
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
* Had evidence of significant renal insufficiency or pre-existing liver condition
* Had platelets ≤ 100 x 10\^9/L, or neutrophil count \< 1.2 x 10\^9/L (or equivalent), hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men.
* Patients who had a known diagnosis of diabetes and are stable on medication with a hemoglobin A1c \> 8%. Those who did not have a known diagnosis of diabetes with a hemoglobin A1c \> 7%.

Primary outcomes:
measure: 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
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
timeFrame: Baseline up to Week 12
measure: Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
timeFrame: Baseline up to Week 12
measure: Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12
timeFrame: Baseline up to Week 12
measure: Number of Participants Per Patient Global Impression of Change Category at Week 12
timeFrame: Baseline up to Week 12
measure: Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
timeFrame: Baseline up to Week 12
measure: Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
timeFrame: Baseline up to Week 12
measure: Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
timeFrame: Baseline up to Week 12
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
timeFrame: Baseline up to Week 12
measure: Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
timeFrame: Week 8, Week 12
measure: Exposure-response (Decrease in Pain Intensity) Via Evaluation of Effect of EMA401 Exposure on Efficacy Variables (e.g. Change From Baseline of Pain Score), Via Descriptive Pharmacokinetics/ Pharmacodynamics (PK/PD)
timeFrame: Baseline, Week 8, Week 12
measure: Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
timeFrame: Approximately from 3 weeks after end of study up to 16 weeks
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Klagenfurt
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Pellenberg
country: Belgium
facility: Novartis Investigative Site
city: Ontario
country: Canada
facility: Novartis Investigative Site
state: CAN
city: Levis
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Chocen
country: Czechia
facility: Novartis Investigative Site
city: Plzen-Bory
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Boulogne Billancourt
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: LILLE Cédex
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein Westfalen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Haar
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Esztergom
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Kistarcsa
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Rome
country: Italy
facility: Novartis Investigative Site
city: Nishinomiya
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Yokohama-shi
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sakai
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kawaguchi-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Shizuoka-shi
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Kasukabe-shi
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Oita
country: Japan
facility: Novartis Investigative Site
city: Seongnam-si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi-do
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Almada
country: Portugal
facility: Novartis Investigative Site
city: Aveiro
country: Portugal
facility: Novartis Investigative Site
city: Leiria
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Dubnica nad Vahom
country: Slovakia
facility: Novartis Investigative Site
state: SVK
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Presov
country: Slovakia
facility: Novartis Investigative Site
city: Spisska Nova Ves
country: Slovakia
facility: Novartis Investigative Site
city: L Hospitalet De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Darlington
country: United Kingdom
facility: Novartis Investigative Site
state: Durham
city: London
country: United Kingdom
facility: Novartis Investigative Site
state: GBR
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Rice ASC, Dworkin RH, Finnerup NB, Attal N, Anand P, Freeman R, Piaia A, Callegari F, Doerr C, Mondal S, Narayanan N, Ecochard L, Flossbach Y, Pandhi S. Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy. Pain. 2021 Oct 1;162(10):2578-2589. doi: 10.1097/j.pain.0000000000002252.