Trial Outcomes & Findings for Evaluation of Cold Sore Treatments on Ultra Violet (UV) Induced Cold Sores (NCT NCT01902303)

Results Overview

The primary efficacy endpoint of this study is to determine if a recurrent oral herpes episode initiated with prodromal symptoms is aborted before progressing to a lesion (vesicle stage) via assessing lesion stages by the trained evaluator. Any episode of oral herpes that did not reach a vesicle stage or higher by Day 7 (based on evaluator and self-assessments of legion stage) was considered "aborted" or "blocked". Any episode of oral herpes that reached a vesicle stage or higher by Day 7 was considered a treatment failure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

303 participants

Primary outcome timeframe

Day 0- Day 7

Results posted on

2016-04-28

Participant Flow

Recruitment occurred from 29Jul2013 through 09Sep2014. Subjects were recruited through three research clinics located in the US who had been trained in UVr application used to trigger recurrent oral Herpes Simplex Labialis.

Subjects who did not meet inclusion/exclusion or withdrew consent prior to enrollment were not enrolled in the study. Eligible subjects underwent minimum erythema dose (MED) UVr determination and if MED criteria was met were randomized. Those enrolled who did not develop prodrome following the UVr induced process were not treated.

Participant milestones

Participant milestones
Measure	Matching Placebo Matching Placebo Treatment regimens will be as follows (upon the first signs/symptoms of prodrome (tingling, itching, burning): * Day 0 - Take 1 drop every 10 minutes for the 1st hour following appearance of prodrome symptoms (0, 10, 20, 30, 40, 50 and 60 minutes), then 1 drop every hour until bedtime. * Days 1 \& 2 - Take 1 drop six times daily - * Days 3-7 - Take one drop twice daily	BTL-TML-HSV Experimental Product BTL-TML-HSV: Sublingual micro dosing of BTL-TML-HSV for 7 days Treatment regimens will be as follows (upon the first signs/symptoms of prodrome (tingling, itching, burning): * Day 0 - Take 1 drop every 10 minutes for the 1st hour following appearance of prodrome symptoms (0, 10, 20, 30, 40, 50 and 60 minutes), then 1 drop every hour until bedtime. * Days 1 \& 2 - Take 1 drop six times daily - * Days 3-7 - Take one drop twice daily
Overall Study STARTED	77	81
Overall Study Number of Participants	56	62
Overall Study COMPLETED	54	57
Overall Study NOT COMPLETED	23	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Matching Placebo Matching Placebo Treatment regimens will be as follows (upon the first signs/symptoms of prodrome (tingling, itching, burning): * Day 0 - Take 1 drop every 10 minutes for the 1st hour following appearance of prodrome symptoms (0, 10, 20, 30, 40, 50 and 60 minutes), then 1 drop every hour until bedtime. * Days 1 \& 2 - Take 1 drop six times daily - * Days 3-7 - Take one drop twice daily	BTL-TML-HSV Experimental Product BTL-TML-HSV: Sublingual micro dosing of BTL-TML-HSV for 7 days Treatment regimens will be as follows (upon the first signs/symptoms of prodrome (tingling, itching, burning): * Day 0 - Take 1 drop every 10 minutes for the 1st hour following appearance of prodrome symptoms (0, 10, 20, 30, 40, 50 and 60 minutes), then 1 drop every hour until bedtime. * Days 1 \& 2 - Take 1 drop six times daily - * Days 3-7 - Take one drop twice daily
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	2	2
Overall Study subject lost investigational product	0	1
Overall Study Did not develop a cold sore	21	19

Baseline Characteristics

Evaluation of Cold Sore Treatments on Ultra Violet (UV) Induced Cold Sores

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Matching Placebo n=77 Participants Placebo Safety Population - All subjects enrolled and received placebo test article	BTL-TML-HSV Active Treatment n=81 Participants BTL-TML Safety Population - All subjects enrolled and received active test article	Total n=158 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	72 Participants n=5 Participants	73 Participants n=7 Participants	145 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	57 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0- Day 7

Population: Participants that did not experience prodrome stage as assessed by the evaluator or met major protocol violations were not included in the PP analysis.

The primary efficacy endpoint of this study is to determine if a recurrent oral herpes episode initiated with prodromal symptoms is aborted before progressing to a lesion (vesicle stage) via assessing lesion stages by the trained evaluator. Any episode of oral herpes that did not reach a vesicle stage or higher by Day 7 (based on evaluator and self-assessments of legion stage) was considered "aborted" or "blocked". Any episode of oral herpes that reached a vesicle stage or higher by Day 7 was considered a treatment failure.

Outcome measures

Outcome measures
Measure	Matching Placebo n=14 Participants Placebo Efficacy Population - All subjects enrolled and received placebo test article and met Per protocol definition	BTL-TML-HSV Active Treatment n=23 Participants BTL-TML Efficacy Population - All subjects enrolled and received active test article and met Per Protocol definition
Number of Participants for Whom a Recurrent Oral Herpes Episode Initiated With Prodromal Symptoms Were Aborted Before Progressing to a Lesion as Assessed by a Trained Evaluator	6 participants who had aborted lesions	11 participants who had aborted lesions

SECONDARY outcome

Timeframe: 0 -7 days

Population: 158 subjects randomized to treatment. 118 subjects used allocated assigned treatment (62 test article and 56 placebo). 7 subjects failed to complete and 111 completed study. For this secondary analysis (self assessments) 53 subjects noted prodrome occurring on Day 0.

The secondary efficacy endpoint of this study is to determine if a recurrent oral herpes episode initiated with prodromal symptoms is aborted before progressing to a lesion (vesicle stage) via assessing lesion stages by the participant. Any episode of oral herpes that did not reach a vesicle stage or higher by Day 7 (based on evaluator and self-assessments of legion stage) was considered "aborted" or "blocked". Any episode of oral herpes that reached a vesicle stage or higher by Day 7 was considered a treatment failure.

Outcome measures

Outcome measures
Measure	Matching Placebo n=28 Participants Placebo Efficacy Population - All subjects enrolled and received placebo test article and met Per protocol definition	BTL-TML-HSV Active Treatment n=25 Participants BTL-TML Efficacy Population - All subjects enrolled and received active test article and met Per Protocol definition
Number of Participants for Whom a Recurrent Oral Herpes Episode Initiated With Prodromal Symptoms Were Aborted Before Progressing to a Lesion as Assessed by the Participant	6 participants with aborted lesions	8 participants with aborted lesions

Adverse Events

Matching Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

BTL-TML-HSV Active Treatment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Matching Placebo n=56 participants at risk；n=222 participants at risk Placebo Safety Population - All subjects that enrolled and were allocated to placebo test article except for SAEs and that includes all subjects that signed informed consent.	BTL-TML-HSV Active Treatment n=62 participants at risk；n=81 participants at risk BTL-TML Safety Population - All subjects enrolled and allocated to active test article except for SAEs which includes all subjects that signed informed consent.
Investigations Blood pressure diastolic increased	5.4% 3/56 • Number of events 3 • AEs were collected from the time of informed consent until end of follow up period which was up to 14 days after start of treatment. Serious AE were collected for all patients. AEs noted over 5% were only for those patients that took study medication.	6.5% 4/62 • Number of events 4 • AEs were collected from the time of informed consent until end of follow up period which was up to 14 days after start of treatment. Serious AE were collected for all patients. AEs noted over 5% were only for those patients that took study medication.
Investigations Heart rate increased	7.1% 4/56 • Number of events 4 • AEs were collected from the time of informed consent until end of follow up period which was up to 14 days after start of treatment. Serious AE were collected for all patients. AEs noted over 5% were only for those patients that took study medication.	3.2% 2/62 • Number of events 2 • AEs were collected from the time of informed consent until end of follow up period which was up to 14 days after start of treatment. Serious AE were collected for all patients. AEs noted over 5% were only for those patients that took study medication.

Additional Information

Dr. John McMichael

Beech Tree Labs, Inc.

Phone: 518-872-1144

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60