Study of 2LHERP® in Genital Herpes Infections

Study Overview
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Brief Summary
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Herpes simplex virus (HSV) infection is very common, as most people will experience herpetic infection during their lifetime. The most common manifestation of HSV infection is sores which may appear at any age. No specific antiviral therapy is available to totally cure herpetic infections and today, there is no treatment that allows the definitive eradication of the virus. The 2LHERP® has been available for more than 20 years, and has received a marketing authorization in Belgium by the FAMHP. It is used as an immune regulator in the treatment of herpetic infections. Since 2LHERP® has been made available, clinical observational data collected on treated patients have shown the beneficial effect on the disappearance of herpetic recurrences. The purpose of this placebo-controlled trial is to evaluate the efficacy of 2LHERP® on the treatment of herpetic infections in adults.

Detailed Description
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The study duration will be maximum 45 months with 33 months of inclusion and 12 months of follow-up. Patients aged between 18 and 80 years who present recurrent genital herpes infections (4 or more episodes within the 12-months' period prior to their study entry). The total number of patients to include will be 100 with 50 patients per group. Primary objective: Evaluation of the efficacy of 2LHERP® on the reduction of the number of recurrent genital herpes infections at 12 months compare to placebo. Secondary objectives: Comparison of the efficacy of 2LHERP® vs placebo, according to the following aspects: number of episodes at 6 months, remaining herpes infection recurrence free 6 and 12 months after the treatment initiation, time to first episode during the treatment, duration of episodes, symptomatology during the entire relapse time, use of Rescue Medication (RM), evaluation of impact on the quality of life, safety issues. Treatment phase: Group n°1 = 2LHERP® (6 months of treatment) Group n°2 = Placebo (6 months of treatment) Post-treatment follow-up phase: 6 months. Treatment will be considered successful if the number of herpetic episodes is reduced.

Official Title
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Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy of 2LHERP® in Patients With Recurrent Genital Herpes Infections

Conditions
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Herpes Simplex, Genital

Intervention / Treatment
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* Drug: 2LHERP®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman aged 18-80 years, Patient presenting 4 or more episodes of genital herpes infections during the preceding 12-months' period (prior to the study entry), Woman of childbearing age under effective contraception, Patient reporting a current stable sexual relationship (steady sexual partner during study duration), Patient having faculties to understand and respect the constraints of the study, Signature of the Informed Consent Form. Exclusion Criteria: Pregnant or breastfeeding woman, Patient under immunotherapy (including immunosuppressive treatment) or micro-immunotherapy received during last previous 6 months, Patient who had a suppressive antiviral therapy during last month, Patient who wishes to continue his/her suppressive antiviral therapy, Patient with known lactose intolerance, Patient who participated in a clinical study in the previous 3-month period, Patient who is not sufficiently motivated to engage in a follow-up period of 12 months, or likely to travel or to move before the end of the study, Patient with severe immunodeficiency disease requiring long term treatment (*) or under chemotherapy or radiotherapy or corticoid therapy, Patient under listed homeopathic or phytotherapy treatment, Patient using or addicted to recreational drugs. (*) important renal or respiratory insufficiency, transplanted or grafted patients, HIV/AIDS, terminal cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2LHERP® arm<br>2LHERP® treatment (6 months of treatment) | Drug: 2LHERP®<br>* The treatment schema consists in taking the content of one capsule a day, 15-30 minutes before breakfast, on an empty stomach, sequentially, according to capsules' numerical order: 1 through 10. When capsule number 10 is taken, capsule 1 of the next blister should be taken on the next day to continue the treatment. The duration of treatment will be 6 months of continuous intake of the content of 1 capsule/day.<br>* Other names: 2LHERP;|
| Placebo Comparator: Placebo arm<br>Placebo treatment (6 months of treatment) | Drug: Placebo<br>* The treatment schema consists in taking the content of one capsule a day, 15-30 minutes before breakfast, on an empty stomach, sequentially, according to capsules' numerical order: 1 through 10. When capsule number 10 is taken, capsule 1 of the next blister should be taken on the next day to continue the treatment. The duration of treatment will be 6 months of continuous intake of the content of 1 capsule/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of 2LHERP® on the reduction of the number of recurrent genital herpes infections at 12 months compare to placebo. | Change from baseline within the number of episodes of genital herpes infection observed for 12 months, where the baseline value is the number of episodes experienced within the 12 months preceeding study enrolment. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the efficacy of 2LHERP® versus placebo according to the number of episodes at 6 months. | Number of episodes of herpes infections observed at month 6 | 6 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to - remaining herpes infection recurrence free 6 and 12 months after the treatment initiation | Patient remaining herpes infection recurrence free 6 months and 12 months after the treatment initiation | 6 and 12 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to the time to first episode during the treatment | Time to first recurrence of herpes infection during the treatment | 6 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to the duration of episodes | Mean duration of episodes, the duration for a given episode being defined as the number of days between the start of the episode and the last day before all symptoms recorded as 'none' for 2 consecutive days, in the patient diary | 6 and 12 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to the symptomatology during the entire relapse time | Level of pain recorded daily on a visual analogue scale (100mm), as well as other associated symptomatology for genital (genital lesions/craks, difficulties to urinate, genital pruritus/burn, fever, QoL), which will be consequently measured as area under the curve (AUC) | 6 and 12 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to the use of Rescue Medication | Use of daily rescue medicine (RM), expressed with the cumulative number of days for the treatment period, the follow-up period and the entire study period | 6 and 12 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to the evaluation of impact on the quality of life | 6-items questionnaire of quality of life | 6 and 12 months | 
| Comparison of the efficacy of 2LHERP® versus placebo according to safety issues | Adverse events (AEs) and severe adverse events (SAEs), considered as related or not to the study drug | 6 months |