Onychomycosis
Conditions
Brief summary
Several properties of VT-1161 suggest that it might be a safer and more effective treatment for onychomycosis of the toenail (also known as toenail fungus) than other oral antifungal medicines. This study will evaluate the effectiveness and safety of VT-1161 for the treatment of toenail onychomycosis and consists of a screening phase, a 24-week treatment phase in which the patient will take either active drug, placebo or a combination of the 2 (according to random assignment), an initial observational phase of 36 weeks and an additional observational study extension of 9 months. The additional 9-month observational study extension was added with a protocol amendment and patient participation was optional.
Interventions
DRUGVT-1161
DRUGPlacebo
Sponsors
Viamet
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Distal subungual onychomycosis of the great toenail, affecting at least ≥25 to ≤75% of nail. Positive culture for dermatophytes and positive KOH. Nail ≤ 3 mm thick at the distal end. At least ≥ 2 mm of the proximal end of the great toenail must be free of infection. Subjects must be able to swallow tablets. Women of childbearing potential and males must use acceptable birth control methods throughout the study. Key
Exclusion criteria
Presence of subungual hematoma or melanonychia. Presence of dermatophytoma/nail streaks and severe onychorrhexis. Significant dystrophy or anatomic abnormalities of the great toenail. Presence of any other infections of the foot. Evidence of clinically significant major organ disease. Poorly controlled diabetes mellitus. Onychomycosis involving more than 8 toe nails. Recent use of systemic antifungal therapy. Recent of any topical antifungal nail therapy. Recent use of systemic corticosteroid therapy. Recent use of immunosuppressive medication. History of prolonged QT intervals. Known human immunodeficiency virus (HIV) infection. Known significant renal or hepatic impairment. Known history of intolerance or hypersensitivity to azole antifungal drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 48 weeks | Complete cure was defined as 0% nail involvement and an Investigator Global Assessment (IGA) score of 0. Mycological cure was defined as negative potassium hydroxide (KOH) and negative dermatophyte culture. Investigator Global Assessment (IGA) scoring: 0: 0% nail involvement 1. \>0% to ≤10% nail involvement 2. \>10% to \<25% nail involvement 3. ≥25% to ≤50% nail involvement 4. \>50% to ≤75% nail involvement 5. \>75% nail involvement |
| Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 9 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 12-week 2 VT-1161 150mg tablets and 2 placebo tablets once daily for 2 weeks, then once weekly for 10 weeks, followed by 4 placebo tablets once weekly for 12 weeks | 53 |
| Low Dose 24-week 2 VT-1161 150mg tablets and 2 placebo tablets once daily for 2 weeks, then once weekly for 22 weeks | 53 |
| High Dose 12-week 4 VT-1161 150mg tablets once daily for 2 weeks, then once weekly for 10 weeks, followed by 4 placebo tablets once weekly for 12 weeks | 52 |
| High Dose 24-week 4 VT-1161 150mg tablets once daily for 2 weeks, then once weekly for 22 weeks | 54 |
| Placebo 4 placebo tablets once daily for 2 weeks, then once weekly for 22 weeks | 47 |
| Total | 259 |
Baseline characteristics
| Characteristic | Low Dose 12-week | Low Dose 24-week | High Dose 12-week | High Dose 24-week | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 9.41 | 50.4 years STANDARD_DEVIATION 10.28 | 49.4 years STANDARD_DEVIATION 12.79 | 49.0 years STANDARD_DEVIATION 10.45 | 52.7 years STANDARD_DEVIATION 11.69 | 50.0 years STANDARD_DEVIATION 10.96 |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 13 Participants | 9 Participants | 9 Participants | 51 Participants |
| Sex: Female, Male Male | 41 Participants | 45 Participants | 39 Participants | 45 Participants | 38 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 53 | 26 / 53 | 31 / 52 | 36 / 54 | 26 / 47 |
| serious Total, serious adverse events | 1 / 53 | 1 / 53 | 2 / 52 | 5 / 54 | 2 / 47 |
Outcome results
Primary
Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose 12-week | Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 8 Participants |
| Low Dose 24-week | Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 5 Participants |
| High Dose 12-week | Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 7 Participants |
| High Dose 24-week | Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 9 Participants |
| Placebo | Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities | 6 Participants |
Primary
The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48
Complete cure was defined as 0% nail involvement and an Investigator Global Assessment (IGA) score of 0. Mycological cure was defined as negative potassium hydroxide (KOH) and negative dermatophyte culture. Investigator Global Assessment (IGA) scoring: 0: 0% nail involvement 1. \>0% to ≤10% nail involvement 2. \>10% to \<25% nail involvement 3. ≥25% to ≤50% nail involvement 4. \>50% to ≤75% nail involvement 5. \>75% nail involvement
Time frame: 48 weeks
Population: Initial 60-week study data. Study extension data not applicable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose 12-week | The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 17 Participants |
| Low Dose 24-week | The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 19 Participants |
| High Dose 12-week | The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 22 Participants |
| High Dose 24-week | The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 18 Participants |
| Placebo | The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | 0 Participants |