Herpes Labialis
Conditions
Keywords
HSV, pritelivir, herpes, herpes labialis, topical,
Brief summary
Randomized, double-blind, multi-center, three arm parallel group, comparative trial to assess pritelivir ointment safety and efficacy, ie, proportion of subjects with non-ulcerative lesions, in adult subjects with recurrent herpes labialis (RHL) in comparison with placebo or Zovirax® Cream. The start of treatment with trial medication will be initiated by the subject within one hour of noticing the first sign or symptom (eg, prodrome) of a recurrence of herpes labialis. Trial medication will be applied to the affected area 5 times daily for 4 days. After self-initiation of treatment with trial medication subjects will be assessed daily by the Investigator until complete healing for a maximum of 13 days. Subjects will document application of trial medication and the status of their lesion in a diary. There will also be blood sampling, ECG measurement and physical examination performed at the investigational site.
Interventions
DRUGPritelivir 5% w/w ointment
DRUGPritelivir ointment matching placebo
DRUGZovirax® cream
Sponsors
Novella Clinical
AiCuris Anti-infective Cures AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy men and women of any ethnic group aged ≥18 years ; * Subjects should have experienced ≥4 recurrences of herpes labialis in the previous 12-months period; * Subjects should have experienced prodromal symptoms in at least 50% of recurrent Herpes labialis (rHL) episodes and should have developed ulcerative lesions that have progressed through vesicle, ulcer, and crust stages in at least 50% of the episodes; * Willingness not to use any topical application (such as cosmetics, lip balm, sunscreens etc…) other than the trial medication in the area of lesion development from start of prodromal symptoms to complete healing; * Willingness not to use any systemic and topical anti-Herpes Simplex Virus (HSV) agent during the trial participation including prescription and over-the-counter (OTC) products; * Willingness not to use any systemic, anti-inflammatory or analgesic agents from start of prodromal symptoms to healing; * Willingness to refrain from mechanical disruption (ie, scrubbing, lancing, shaving) of the prodromal area or lesion after start of treatment with trial medication until end of the trial participation; * Women of child bearing potential and males must use adequate contraception; * Subject must give written informed consent. * Subjects with current lesion may be enrolled, but they must not treat the lesion present at screening/randomization with the trial medication; they should be instructed to wait for their next subsequent lesion
Exclusion criteria
* Known intolerance to pritelivir or any of the ointment ingredients; * Known intolerance to Zovirax® Cream or any of the ingredients (ie, acyclovir, cetostearyl alcohol, mineral oil, poloxamer 407, propylene glycol, sodium lauryl sulfate, and white petrolatum) or valacyclovir; * Any skin conditions that could interfere with the assessment of herpes labialis recurrences (eg, eczema, psoriasis, acne etc…) * Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial * Pregnant and/or breastfeeding women * Participation in any investigational drug trial within the last 30 days before randomization for this clinical trial * Previous treatment with pritelivir tablets * Previous participation in a HSV vaccination Trial unless having received placebo. * Clinically relevant ECG abnormalities (eg, QTc according to Fridericia: QTcF \> 450 ms for males and QTcF \> 470 ms for females; PR \> 220 ms) at screening. * Clinically relevant abnormalities in laboratory indices at screening which in the opinion of the investigator might have an impact on the safety and evaluability of the subject. * Known chronic infections which in the opinion of the investigator might have an impact on the safety and evaluability of the subject. * Evidence of active malignancy or immunodeficiency disease, or require chronic use of immunosuppressive drugs (eg, systemic steroids) or topical steroids, or chronically use antiviral medication with activity against HSV. * HIV positive based on screening labs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | 13 days | The Investigator assessed subjects for lesion stage at every visit as long as lesions were present from Visit 1 to the End of Trial Visit (Day 12± 1) as a maximum. Percentage of subjects with non-ulcerative lesions (i.e, scoring below 3) based on the Principal Investigators Assessment. Lesion stages were defined as follows: 1-Prodrome; 2a-Redness; 2b-Erythema-Redness; 3-Small Blister; 4-Ulcer; 5-Crust; 6-Drying up and healing; 0-Resolved |
Countries
United States
Participant flow
Recruitment details
Patients with labial HSV develop an outbreak only a few times per year. Therefore, more patients need to be enrolled to obtain the planned number of evaluable herpes labialis recurrences, as roughly 40% of subjects do not develop a recurrence. Overall, 362 subjects were enrolled and randomized. 223 started the self-initiated treatment due to an outbreak. The remaining 139 subjects did not have an outbreak and were not treated.
Participants by arm
| Arm | Count |
|---|---|
| Pritelivir 5% w/w Ointment Topical treatment (20 applications), 5 times daily for 4 days
Pritelivir 5% w/w ointment | 73 |
| Pritelivir Ointment Matching Placebo Topical treatment (20 applications), 5 times daily for 4 days
Pritelivir ointment matching placebo | 73 |
| Zovirax® Cream Topical treatment (20 applications), 5 times daily for 4 days
Zovirax® cream | 77 |
| Total | 223 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 3 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Pritelivir 5% w/w Ointment | Pritelivir Ointment Matching Placebo | Zovirax® Cream | Total |
|---|---|---|---|---|
| Age, Continuous | 54 years | 49 years | 51 years | 51 years |
| BMI | 27.8 kg/m^2 | 27.3 kg/m^2 | 28.1 kg/m^2 | 27.8 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 6 Participants | 10 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 63 Participants | 65 Participants | 65 Participants | 193 Participants |
| Region of Enrollment United States | 73 Participants | 73 Participants | 77 Participants | 223 Participants |
| Sex: Female, Male Female | 52 Participants | 53 Participants | 56 Participants | 161 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 21 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 73 | 0 / 73 | 0 / 77 |
| other Total, other adverse events | 30 / 73 | 27 / 73 | 27 / 77 |
| serious Total, serious adverse events | 0 / 73 | 0 / 73 | 0 / 77 |
Outcome results
Primary
Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment
The Investigator assessed subjects for lesion stage at every visit as long as lesions were present from Visit 1 to the End of Trial Visit (Day 12± 1) as a maximum. Percentage of subjects with non-ulcerative lesions (i.e, scoring below 3) based on the Principal Investigators Assessment. Lesion stages were defined as follows: 1-Prodrome; 2a-Redness; 2b-Erythema-Redness; 3-Small Blister; 4-Ulcer; 5-Crust; 6-Drying up and healing; 0-Resolved
Time frame: 13 days
Population: Primary analysis for the ITT ( intent to treat) population; multiple imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pritelivir 5% w/w Ointment | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Non-ulcerative recurrences | 21.8 percentage of partcipants |
| Pritelivir 5% w/w Ointment | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Ulcerative recurrences | 78.2 percentage of partcipants |
| Pritelivir Ointment Matching Placebo | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Non-ulcerative recurrences | 16.4 percentage of partcipants |
| Pritelivir Ointment Matching Placebo | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Ulcerative recurrences | 83.6 percentage of partcipants |
| Zovirax® Cream | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Non-ulcerative recurrences | 19.9 percentage of partcipants |
| Zovirax® Cream | Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment | Ulcerative recurrences | 80.1 percentage of partcipants |
p-value: 0.4294Cochran-Mantel-Haenszel