E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Viral meningitis caused by Herpes simplex virus 2 |
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E.1.1.1 | Medical condition in easily understood language |
Meningitis caused by Herpes simplex virus type 2. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047469 |
E.1.2 | Term | Viral meningitis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To examine if active treatment with intravenous aciclovir or tablet valaciclovir is superior to placebo in treatment of HSV-2 meningitis |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adults ≥18 years of age admitted on suspicion of viral meningitis defined as:
1. A clinical presentation consistent with viral meningitis (e.g. headache, nuchal rigidity, photophobia, or fever) AND
2. Cerebrospinal fluid (CSF) pleocytosis (>4 leukocytes x 106/L) AND
3. Glasgow Coma Scale score of 15 AND
4. Ability to absorb oral medications |
|
E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria will be excluded:
1. Encephalitis as defined by the International Encephalitis Consortium if diagnosed during standard care.
2. Transverse myelitis as defined by the Transverse Myelitis Consortium Working Group if diagnosed during standard care.
3. Severe immuno-compromise defined as an ongoing need for biological- or chemotherapy (e.g. natalizumab), prednisolone >20 mg/day for ≥14 days, uncontrolled HIV/AIDS (see glossary), haematological malignancies, and organ transplant recipients.
4. Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)
5. Hepatic impairment (aspartate aminotransferase or alanine aminotransferase levels >5 times the upper limit of normal)
6. Impaired renal function (estimated glomerular filtration rate <25 mL/min)
7. Intolerance to (val)aciclovir
8. Probenecid treatment
9. Systemic antiviral therapy with an antiherpetic effect for >24 hours
10. Previous enrolment into this trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Total morbidity score (TMS) >6.
The TMS is calculated as the sum of scores for the following symptoms:
1. Headache (0=none to 6=incapacitating) 2. Nuchal rigidity (0 to 4) 3. Photophobia (0 to 4) 4. Myalgia (0 to 4) 5. Fever (0 to 4) 6. Nausea (0 to 4)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
10 days after randomisation |
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E.5.2 | Secondary end point(s) |
Proportion of patients with <50% reduction in TMS score after 10 days compared with TMS score at randomisation.
Extended Glasgow Outcome Scale score at 10 days, 3 months and 12 months since randomisation.
Quality of life scores and cognitive evaluations at 10 days, 3 months and 12 months since randomisation.
Persisting neurological symptoms at 10 days, 3 months and 12 months since randomisation.
Completion of assigned treatment.
Peripheral venous line associated complicatoins.
Severe adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Plese see specification above under secondary endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
France |
Netherlands |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject undergoing the trial, expected 31.12.2024. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |