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

NCT ID: NCT03094195

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-27
• Study Completion Date: 2019-03-07

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.

Conditions

Post-herpetic Neuralgia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EMA401 25mg BID

Ema401 25 mg was administered orally twice a day

Group Type: EXPERIMENTAL

EMA401

Intervention Type: DRUG

EMA401

EMA401 100mg BID

Ema401 100 mg was administered orally twice a day

Group Type: EXPERIMENTAL

EMA401

Intervention Type: DRUG

EMA401

Placebo BID

Matching placebo capsules administered orally twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

EMA401

EMA401

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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%.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Klagenfurt, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Pellenberg, , Belgium

Novartis Investigative Site

Ontario, CAN, Canada

Novartis Investigative Site

Lévis, Quebec, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Brno, , Czechia

Novartis Investigative Site

Choceň, , Czechia

Novartis Investigative Site

Plzen-Bory, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Odense C, , Denmark

Novartis Investigative Site

Boulogne-Billancourt, , France

Novartis Investigative Site

Clermont-Ferrand, , France

Novartis Investigative Site

Lille Cédex, , France

Novartis Investigative Site

Nice, , France

Novartis Investigative Site

Essen, North Rhine-Westphalia, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Haar, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Wiesbaden, , Germany

Novartis Investigative Site

Esztergom, HUN, Hungary

Novartis Investigative Site

Kistarcsa, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Rome, , Italy

Novartis Investigative Site

Nishinomiya, Hyōgo, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Sakai, Osaka, Japan

Novartis Investigative Site

Kawaguchi, Saitama, Japan

Novartis Investigative Site

Shizuoka, Shizuoka, Japan

Novartis Investigative Site

Kasukabe-shi, Tokyo, Japan

Novartis Investigative Site

Setagaya Ku, Tokyo, Japan

Novartis Investigative Site

Ōita, , Japan

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Olsztyn, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Almada, , Portugal

Novartis Investigative Site

Aveiro, , Portugal

Novartis Investigative Site

Leiria, , Portugal

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Dubnica nad Váhom, SVK, Slovakia

Novartis Investigative Site

Banská Bystrica, , Slovakia

Novartis Investigative Site

Prešov, , Slovakia

Novartis Investigative Site

Spišská Nová Ves, , Slovakia

Novartis Investigative Site

Seongnam-si, Gyeonggi-do, South Korea

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Tainan City, , Taiwan

Novartis Investigative Site

Darlington, Durham, United Kingdom

Novartis Investigative Site

London, GBR, United Kingdom

Novartis Investigative Site

Liverpool, , United Kingdom

Countries

Australia; Austria; Belgium; Canada; Czechia; Denmark; France; Germany; Hungary; Italy; Japan; Norway; Poland; Portugal; Slovakia; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33675631 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=623

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

CEMA401A2201

Identifier Type: -

Identifier Source: org_study_id