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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03094195
Other study ID # CEMA401A2201
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date June 27, 2017
Est. completion date March 7, 2019

Study information

Verified date October 2021
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 130
Est. completion date March 7, 2019
Est. primary completion date March 7, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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%.

Study Design


Intervention

Drug:
EMA401
EMA401
Placebo
Placebo

Locations

Country Name City State
Australia Novartis Investigative Site Melbourne Victoria
Austria Novartis Investigative Site Klagenfurt
Austria Novartis Investigative Site Vienna
Belgium Novartis Investigative Site Pellenberg
Canada Novartis Investigative Site Levis Quebec
Canada Novartis Investigative Site Ontario CAN
Canada Novartis Investigative Site Quebec
Czechia Novartis Investigative Site Brno
Czechia Novartis Investigative Site Chocen
Czechia Novartis Investigative Site Plzen-Bory
Czechia Novartis Investigative Site Praha 10
Denmark Novartis Investigative Site Odense C
France Novartis Investigative Site Boulogne Billancourt
France Novartis Investigative Site Clermont-Ferrand
France Novartis Investigative Site LILLE Cédex
France Novartis Investigative Site Nice
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Dresden
Germany Novartis Investigative Site Erlangen
Germany Novartis Investigative Site Essen Nordrhein Westfalen
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
Hungary Novartis Investigative Site Esztergom HUN
Hungary Novartis Investigative Site Kistarcsa
Hungary Novartis Investigative Site Szeged
Italy Novartis Investigative Site Rome
Japan Novartis Investigative Site Kasukabe-shi Tokyo
Japan Novartis Investigative Site Kawaguchi-city Saitama
Japan Novartis Investigative Site Nishinomiya Hyogo
Japan Novartis Investigative Site Oita
Japan Novartis Investigative Site Sakai Osaka
Japan Novartis Investigative Site Setagaya ku Tokyo
Japan Novartis Investigative Site Shizuoka-shi Shizuoka
Japan Novartis Investigative Site Yokohama Kanagawa
Japan Novartis Investigative Site Yokohama Kanagawa
Japan Novartis Investigative Site Yokohama-shi Kanagawa
Korea, Republic of Novartis Investigative Site Seongnam-si Gyeonggi-do
Norway Novartis Investigative Site Oslo
Poland Novartis Investigative Site Olsztyn
Poland Novartis Investigative Site Warszawa
Portugal Novartis Investigative Site Almada
Portugal Novartis Investigative Site Aveiro
Portugal Novartis Investigative Site Leiria
Portugal Novartis Investigative Site Lisboa
Portugal Novartis Investigative Site Porto
Slovakia Novartis Investigative Site Banska Bystrica
Slovakia Novartis Investigative Site Dubnica nad Vahom SVK
Slovakia Novartis Investigative Site Presov
Slovakia Novartis Investigative Site Spisska Nova Ves
Spain Novartis Investigative Site Barcelona
Spain Novartis Investigative Site L Hospitalet De Llobregat Barcelona
Taiwan Novartis Investigative Site Tainan
United Kingdom Novartis Investigative Site Darlington Durham
United Kingdom Novartis Investigative Site Liverpool
United Kingdom Novartis Investigative Site London GBR

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
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 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. Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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 Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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 Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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. Baseline up to Week 12
Secondary 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 Week 8, Week 12
Secondary 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 Baseline, Week 8, Week 12
Secondary 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 Approximately from 3 weeks after end of study up to 16 weeks
See also
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