Aciclovir for HSV-2 MENingitis: A double-blinded randomised controlled trial (AMEN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-01-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-520042-31-00

EudraCT number

2020-000033-41

ClinicalTrials.gov

NCT05452928

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To determine whether active treatment with (val)acyclovir is superior for treatment of viral meningitis compared with placebo assessed by number of patients with a Total Morbidity Score (TMS) >6 at 7 days after randomisation

Secondary objectives 1

1. To determine the proportions of patients with favourable outcome during 3 months of follow-up, completion of allocated treatment (oral or IV), safety, and quality of life assessed by secondary endpoints

Conditions and MedDRA coding

HSV-2 meningitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. A clinical presentation consistent with viral meningitis (e.g. headache, nuchal rigidity, photophobia, or fever)
2. Cerebrospinal fluid (CSF) pleocytosis (>4 leukocytes x 106/L)
3. HSV-2 positive by PCR of the CSF
4. Glasgow Coma Scale score of 15
5. Ability to absorb oral medications

Exclusion criteria 11

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, haematological malignancies, and organ transplant recipients
4. Moderate to severe concomitant genital herpes requiring systemic aciclovir
5. Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)
6. Hepatic impairment (aspartate aminotransferase or alanine aminotransferase levels >5 times the upper limit of normal)
7. Impaired renal function (estimated glomerular filtration rate <25 mL/min)
8. Intolerance to (val)aciclovir
9. Probenecid treatment
10. Systemic antiviral therapy with an antiherpetic effect for >24 hours
11. Previous enrolment into this trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome in the current study is the proportion of patients with a TMS >6 at 7 days since randomisation.

Secondary endpoints 9

1. Proportion of patients with ≤50% reduction in TMS score after 7 days compared with TMS score at randomisation
2. Unfavourable outcome (E-GOS <7) and all-cause mortality at 7 days, 3 and 12 months since randomisation
3. Proportion with a headache score of >2 at 7 days since randomisation
4. Persisting neurological symptoms (sensory or motor nerve) at 7 days, 3 and 12 months since randomisation
5. Completion of assigned treatment strategy
6. Peripheral venous line complications (infection or superficial venous thrombosis) during treatment
7. Duration of admission
8. Severe adverse events during treatment
9. Quality of life scores and cognitive evaluations (SF-36, EQ-5D-5L, Mental fatigue Scale) at 7 days as well as 3- and 12-months since randomisation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Moelleparkvej 4

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Jacob Bodilsen

Public contact point

Organisation

Aalborg University Hospital

Contact name

Jacob Bodilsen

Third parties 1

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications