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Post-herpetic NeuralgiaPhase 2EMPHENENCT03094195

Dose Response Study of EMA401 in Patients With Post-herpetic Neuralgia (PHN)

A Phase 2 study testing EMA401 in people with Post-herpetic Neuralgia, run by Novartis Pharmaceuticals at 58 sites in 19 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Post-herpetic Neuralgia
What is being tested?
EMA401
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
130 participants
Where
58 sitesin 19 countries
Study dates
27 Jun 2017to 7 Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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%.

Trial locations and contacts

58 sites in 19 countries.

58 sites in 19 countries

Japan10 sites
  • Novartis Investigative Site

    Kasukabe-shi, Tokyo, 343-0012

  • Novartis Investigative Site

    Kawaguchi, Saitama

  • Novartis Investigative Site

    Nishinomiya, Hyōgo, 663 8014

  • Novartis Investigative Site

    Ōita

  • Novartis Investigative Site

    Sakai, Osaka, 593-8324

  • Novartis Investigative Site

    Setagaya Ku, Tokyo, 154-0015

  • Novartis Investigative Site

    Shizuoka, Shizuoka, 420-0839

  • Novartis Investigative Site

    Yokohama, Kanagawa, 241-0022

  • Novartis Investigative Site

    Yokohama, Kanagawa, 244-0816

  • Novartis Investigative Site

    Yokohama, Kanagawa, 245-8575

Other trials in Japan

Germany9 sites
  • Novartis Investigative Site

    Berlin, 10435

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Essen, North Rhine-Westphalia, 45147

  • Novartis Investigative Site

    Haar, 85540

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Kiel, 24119

  • Novartis Investigative Site

    Leipzig, 04109

  • Novartis Investigative Site

    Wiesbaden, 65191

Other trials in Germany

Portugal5 sites
  • Novartis Investigative Site

    Almada, 2801 951

  • Novartis Investigative Site

    Aveiro, 3814-501

  • Novartis Investigative Site

    Leiria, 2410-187

  • Novartis Investigative Site

    Lisbon, 1500 650

  • Novartis Investigative Site

    Porto, 4099-001

Other trials in Portugal

Czechia4 sites
  • Novartis Investigative Site

    Brno, 615 00

  • Novartis Investigative Site

    Choceň, 56501

  • Novartis Investigative Site

    Plzen-Bory, 305 99

  • Novartis Investigative Site

    Prague, 100 00

Other trials in Czechia

France4 sites
  • Novartis Investigative Site

    Boulogne-Billancourt, 92104

  • Novartis Investigative Site

    Clermont-Ferrand, 63000

  • Novartis Investigative Site

    Lille Cédex, 59037

  • Novartis Investigative Site

    Nice, 06003

Other trials in France

Slovakia4 sites
  • Novartis Investigative Site

    Banská Bystrica, 974 04

  • Novartis Investigative Site

    Dubnica nad Váhom, SVK, 018 41

  • Novartis Investigative Site

    Prešov, 08001

  • Novartis Investigative Site

    Spišská Nová Ves, 05201

Other trials in Slovakia

Canada3 sites
  • Novartis Investigative Site

    Lévis, Quebec, G6W 5M6

  • Novartis Investigative Site

    Ontario, CAN, L4J 1W3

  • Novartis Investigative Site

    Québec, Quebec, G3K 2P8

Other trials in Canada

Hungary3 sites
  • Novartis Investigative Site

    Esztergom, HUN, 2500

  • Novartis Investigative Site

    Kistarcsa, 2143

  • Novartis Investigative Site

    Szeged, 6725

Other trials in Hungary

United Kingdom3 sites
  • Novartis Investigative Site

    Darlington, Durham, DL3 6HX

  • Novartis Investigative Site

    Liverpool, L9 7LJ

  • Novartis Investigative Site

    London, GBR, SW10 9NH

Other trials in United Kingdom

Austria2 sites
  • Novartis Investigative Site

    Klagenfurt, 9020

  • Novartis Investigative Site

    Vienna, A-1160

Other trials in Austria

Poland2 sites
  • Novartis Investigative Site

    Olsztyn, 10 561

  • Novartis Investigative Site

    Warsaw, 00 144

Other trials in Poland

Spain2 sites
  • Novartis Investigative Site

    Barcelona, 08025

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

Other trials in Spain

Australia1 site
  • Novartis Investigative Site

    Melbourne, Victoria, 3000

Other trials in Australia

Belgium1 site
  • Novartis Investigative Site

    Pellenberg, 3212

Other trials in Belgium

Denmark1 site
  • Novartis Investigative Site

    Odense C, DK 5000

Other trials in Denmark

Italy1 site
  • Novartis Investigative Site

    Rome, 00185

Other trials in Italy

Norway1 site
  • Novartis Investigative Site

    Oslo, 0450

Other trials in Norway

South Korea1 site
  • Novartis Investigative Site

    Seongnam-si, Gyeonggi-do, 463-712

Other trials in South Korea

Taiwan1 site
  • Novartis Investigative Site

    Tainan, 70403

Other trials in Taiwan

About this study

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

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).

Read the 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.

Being tested
EMA401, Placebo
Keywords
post-herpetic neuralgia, neuropathic pain, angiotensin II type 2 receptor antagonist, dose ranging
Medical subject headings
Neuralgia, Postherpetic, Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EMA401Drug

    EMA401

  • PlaceboDrug

    Placebo

Study groups in NCT03094195
Study groupRoleWhat they receive
EMA401 25mg BIDExperimentalEma401 25 mg was administered orally twice a day
Receives: Drug: EMA401
EMA401 100mg BIDExperimentalEma401 100 mg was administered orally twice a day
Receives: Drug: EMA401
Placebo BIDPlacebo comparatorMatching placebo capsules administered orally twice a day
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Since the 300 mg b.i.d. dose of EMA401 could not be initiated in the study due to premature study termination, the dose-response characterization was not performed. Specifically, only the trend test deduced from the set of candidate models was performed but the dose response estimation was not conducted.

    Measured: Baseline up to Week 12

Secondary outcomes (11)
  1. Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12

    The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.

    Measured: Baseline up to Week 12

  2. Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12

    The BPI-SF is a validated, self-administered (at clinic) questionnaire that assesses pain severity and its mpact on daily functions. Patients were asked to complete the 7-item pain interference scale that assessed the degree to which pain interfered with walking and other physical activity, work, mood, relations with others and sleep using a zero to ten numeric rating scale (NRS) with zero being "does not interfere" and ten being "completely interferes". A reduction in mean indicates improvement

    Measured: Baseline up to Week 12

  3. Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12

    The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.

    Measured: Baseline up to Week 12

  4. Number of Participants Per Patient Global Impression of Change Category at Week 12

    The Patient Global Impression of Change (PGIC) is a patient-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse"). The PGIC is based on the validated Clinical Global Impression of Change scale. The PGIC was to be completed by patients using the electronic tablet at the site

    Measured: Baseline up to Week 12

  5. Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale

    The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The number of patients with observed response, i.e. a decrease of 30% /50% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio >1 = higher chance of a clinically important improvement.

    Measured: Baseline up to Week 12

  6. Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale

    The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The number of patients with observed response, i.e. a decrease of 50% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio >1 = higher chance of a clinically important improvement.

    Measured: Baseline up to Week 12

  7. Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12

    Patients were asked to complete the ISI using five-point Likert-style scale as a measure of perceived sleep difficulties. Scores ranged from zero to 28, with a cut-off score of eight suggesting the presence of sub-threshold insomnia. The questionnaire assessed the severity of insomnia, satisfaction with current sleep pattern, sleep interference, "noticeability" of sleeping problem to others and concern about sleeping problems.

    Measured: Baseline up to Week 12

  8. Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12

    The Neuropathic Pain Symptom Inventory (NPSI) is a 12 item patient reported outcome measure that contains 10 descriptors representing 5 dimensions of pain (burning pain, deep/pressing pain, paroxysmal pain, evoked pain and paraesthesia/dysesthesia) and 2 temporal items designed to assess pain duration and the number of pain paroxysms. The sum of the responses to the 10 questions (all except temporal questions) was regarded as the total score and was divided by 10 (10 questions). The range of the total score and of the 5 dimensional scores is 0 to 10. Lower values represent better outcomes.

    Measured: Baseline up to Week 12

  9. Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12

    Due to the premature termination of the study, the number of patients and observations providing PK data was much smaller than planned, and no PK model was developed. As a consequence, no PK parameters (Cmax, Tmax, AUC) were derived for this study. Only, summary statistics of the plasma concentrations were calculated

    Measured: Week 8, Week 12

  10. 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)

    Due to the premature termination of the study, the number of patients providing data for PKPD analysis data was much smaller than planned and no model to correlate drug exposure (PK) with the change in the pain score (PD) was developed

    Measured: Baseline, Week 8, Week 12

  11. Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up

    Participants were instructed to stop taking drug immediately upon termination of study and asked to come in for two unscheduled visits for follow up safety assessments

    Measured: Approximately from 3 weeks after end of study up to 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2017
  2. Study start27 Jun 2017
  3. Primary completion7 Mar 2019
  4. Study completion7 Mar 2019

Why it stopped: The study was terminated early due to pre-clinical toxicity data that became available after start of trial

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03094195
Sponsor's protocol ID
CEMA401A2201
Acronym
EMPHENE
Status last verified
Oct 2021
First submitted
23 Mar 2017
Last updated
8 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • 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.

    PubMed 33675631

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing EMA401 in people with Post-herpetic Neuralgia, run by Novartis Pharmaceuticals at 58 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in Japan, Germany, Portugal, Czechia, France and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Baseline up to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03094195, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.

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