This is a phase II, double-blind, randomised, controlled, multicentre trial of topical HDIT101 versus placebo.
Approximately 138 eligible patients will be randomised at a ratio of 2:1 to topical HDIT or corresponding placebo.
The trial consists of 3 parts: An observation phase (up to 9 months), a treatment phase of 12 months, and a post-trial follow-up phase of additional 12 months: The observation phase ensures that the patient develops a minimum number of lesions during the trial. In the 12 months treatment phase, blinded study treatment consisting of topical HDIT101 or placebo is applied to the patients at the first and second lesion episode. After completion of the treatment phase, patients are followed for additional 12 months for assessment of the development of further lesions (post-trial follow-up phase).
Observation phase (max. 9 months):
Eligible patients suffering from chronic recurrent herpes orolabialis for at least 12 months and reporting ≥ 6 lesions in the last 12 months can enter the observation phase. This part of the study serves for confirmation that patients develop a minimum number of 3 lesions within the 9 months observation period. No study treatment is applied in the observation phase, but standard-of-care treatment (SoC) can optionally be applied. Single swabs should additionally be taken from the lesion for confirmation of HSV-1 positivity.
Patients not developing 3 lesions with an HSV lesion score 3-7 during the 9 months observation phase are considered screening failures and will not be randomised into the treatment part of the trial.
Randomised, double-blind treatment phase (12 months):
This phase consists of four scheduled visits (day 30/120/240/365) and unscheduled visits for treatment of lesion 3 and 4, respectively.
Patients who have developed 3 outbreaks within the observational phase will enter the treatment phase. The third of these lesions will already be treated. Notably, patients do not have to complete the 9 months observation phase if they develop the 3rd lesion earlier - treatment starts with occurrence of a 3rd lesion.
With the occurrence of lesion 3 within the 9 months observation phase, patients need to schedule a visit at the study site when a vesicle is present. If the patient meets all inclusion criteria, randomisation takes place. An electronic patient reported outcome (ePRO) tool will be installed on the patients' devices and questionnaires will be answered. The lesion will be documented in the ePRO app with a photo. A swab of the lesion will be taken which preferably should contain fluid from the vesicular lesion. Subsequently, blinded IMP will be applied to the lesion. The investigator will determine the lesion start and end date based on information provided by the patient. 3 additional vials of study IMP for further treatment of this lesion will be handed over to the patient for self-application.
Upon occurrence of a fourth lesion in the treatment phase, the same procedure will be repeated at another unscheduled visit at the site when a vesicle is present. Again, IMP will be handed over to the patient for further treatment of this lesion.
All subsequent lesions occurring during the 12 months treatment phase need to be documented by the patient by photos and questionnaires. At each lesion episode, single swabs will be taken, but no further IMP will be applied and no unscheduled visit is necessary, but phone calls. The investigator will assess and medically confirm the lesion to be herpes-related and will determine the lesion start and end date based on information and photos provided by the patient and patient entries in the ePRO. Standard-of-care treatment (SoC) can optionally be applied.
Treatments and Examinations during the Study:
During all phases of the trial, patients need to report disease-specific symptoms and outbreak impact upon recognition of first symptoms during the study.
Orolabial viral shedding of patients is assessed by quantitative real time polymerase chain reaction (qRT-PCR) derived from swabs. These will be taken daily for 28 days in the orolabial region during the 9 months observation period starting after lesion 2, at occurrence of lesion 3 at visit 3 and 4 months after randomisation (starting at visit 5), respectively.
Each lesion recurrence has to be documented by the patient in the patient eDiary. In case of development of new lesions after lesion 3 or 4, patients will be instructed to take a swab of the lesion and provide this to the site for HSV-1 PCR outbreak confirmation. The patients must take photos (preferably daily) of the lesion until healing. These photos will be transferred to the sites' source data. The investigator will assess and medically confirm the lesion to be herpes-related and will determine the lesion start and end date based on information and photos provided by the patient and patient entries in the electronic diary.
Lesions will be rated according to a lesion score. For every lesion episode (outbreak), patients will be asked to report disease specific symptoms and outbreak impact in electronic questionnaires on a daily basis, from recognition of first symptoms until complete resolution of the symptoms.
Post-trial follow-up phase (12 months):
After the treatment phase, patients are further followed-up by phone every 3 months for a total duration of additional 12 months.
