Inflammatory Acne
Conditions
Keywords
Acne, efficacy, safety
Brief summary
The main purpose of this study is to assess preliminary efficacy and safety of LYS006 in patients with moderate to severe inflammatory acne and to determine if LYS006 has an adequate clinical profile for further clinical development.
Detailed description
This was a randomized, placebo-controlled, subject- and investigator-blinded, multicenter, nonconfirmatory, parallel group, and proof-of-concept study in adult patients with moderate to severe inflammatory acne. After an initial screening period (up to 4 weeks), subjects were treated with LYS006 or matching placebo for 12 consecutive weeks to assess preliminary clinical efficacy, safety, and tolerability in the targeted subject population. At the beginning of the treatment period, subjects were randomized to one of three treatment groups, i.e., LYS006 20 mg twice daily (BID), LYS006 2 mg BID or matching placebo in a 3:1:3 ratio. After treatment period completion, all subjects entered a post-treatment safety follow-up period of 4 weeks without study drug administration. The maximum duration of study participation was 20 weeks. Study completion was defined as when the last subject completed his/her study completion visit, and any repeat assessments associated with this visit were documented and followed-up appropriately by the investigator, or in the event of an early study termination decision, the date of that decision.
Interventions
DRUGLYS006 20 mg
LYS006 20 mg, capsules, oral administration, BID, for 12 weeks
DRUGLYS006 2 mg
LYS006 2 mg, capsules, oral administration, BID, for 12 weeks
DRUGPlacebo
Matching placebo, capsules, oral administration, BID, for 12 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged 18 to 45 years of age inclusive, and otherwise in good health as determined by medical history, physical examination, vital signs, ECGs and laboratory tests at screening. * Body weight between 50 and 120 kg, both inclusive, at screening. * Patients with papulo-pustular acne vulgaris (inflammatory acne) presenting with 20 to 100 facial inflammatory lesions (papules, pustules and nodules) at baseline, no more than 2 facial inflammatory nodules or cysts at screening and baseline, and a minimun number of 10 non-inflammatory facial lesions (open and closed comedones). * Patients who are candidates for systemic treatment and for whom in the opinion of the investigator, an appropriate previous treatment with topical anti-acne medication failed, or was not well tolerated, or is not indicated (e.g., due to large body surface area affected, e.g., on the back) * Patients with Grade 3 (moderate) or Grade 4 (severe) IGA score assessed by the investigator at screening and baseline.
Exclusion criteria
* Appropriate wash out periods are required for investigational drugs, any oral/systemic treatment for acne, systemic or lesional injected (for acne) corticosteroids or systemic immunomodulators, any systemic hormonal treatments, previous treatment with biologics, oral retinoids (in particular isotretinoin) and any topical anti-acne treatment. * Previous surgical, physical (such as ThermaClear™), light (including blue or UV light, photodynamic therapy or laser therapy within 4 weeks prior to baseline * Use of facial medium depth chemical peels (excluding home regimens) within 3 months prior to baseline. * Any other forms of acne * Any severe, progressive or uncontrolled medical or psychiatric condition or other factors at randomization that in the judgment of the investigator prevents the patient from participating in the study. * Active systemic infections (other than common cold) during the 2 weeks prior to baseline. * History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result at screening. * Chronic infection with Hepatitis B or Hepatitis C virus. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human chorionic gonadotropin (HCG) laboratory test. * Sexually active males or women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Inflammatory Lesion Count | Week 12 | Inflammatory facial lesion count included papules, pustules, and nodules. The natural log transformed inflammatory facial lesion count up to Week 12 was analyzed using a Bayesian mixed effect model for repeated measurements (MMRM). Values estimated from the model at Week 12 are presented in the table. Posterior geometric mean and 90% credible intervals in each group are presented. |
Countries
Czechia, France, Germany, Hungary, Netherlands, United States
Participant flow
Recruitment details
Participants took part in 18 investigative sites in 6 countries.
Pre-assignment details
There was an initial screening period of up to 4 weeks.
Participants by arm
| Arm | Count |
|---|---|
| LYS006 20 mg BID LYS006, 20 mg, orally, twice daily (BID), for 12 weeks | 26 |
| LYS006 2 mg BID LYS006, 2 mg, orally, BID, for 12 weeks | 11 |
| Placebo BID Matching placebo, orally, BID, for 12 weeks | 29 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Subject/Guardian Decision | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | LYS006 20 mg BID | LYS006 2 mg BID | Placebo BID |
|---|---|---|---|---|
| Age, Continuous | 24.2 years STANDARD_DEVIATION 6.13 | 23.2 years STANDARD_DEVIATION 6.89 | 24.5 years STANDARD_DEVIATION 6.23 | 25.0 years STANDARD_DEVIATION 5.4 |
| Race/Ethnicity, Customized Asian | 3 participants | 1 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 9 participants | 2 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized Other | 9 participants | 2 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized White | 45 participants | 21 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 46 Participants | 16 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Male | 20 Participants | 10 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 11 | 0 / 29 | 0 / 66 |
| other Total, other adverse events | 10 / 26 | 8 / 11 | 16 / 29 | 34 / 66 |
| serious Total, serious adverse events | 0 / 26 | 0 / 11 | 0 / 29 | 0 / 66 |
Outcome results
Primary
Total Inflammatory Lesion Count
Inflammatory facial lesion count included papules, pustules, and nodules. The natural log transformed inflammatory facial lesion count up to Week 12 was analyzed using a Bayesian mixed effect model for repeated measurements (MMRM). Values estimated from the model at Week 12 are presented in the table. Posterior geometric mean and 90% credible intervals in each group are presented.
Time frame: Week 12
Population: Participants in the PD analysis set who had a valid assessment of the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LYS006 20 mg BID | Total Inflammatory Lesion Count | 18.55 lesions |
| LYS006 2 mg BID | Total Inflammatory Lesion Count | 24.51 lesions |
| Placebo BID | Total Inflammatory Lesion Count | 20.04 lesions |
90% CI: [0.64, 1.34]Bayesian analysis
Bayesian analysis
Bayesian analysis