Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, Safety, Efficacy, Atopic Eczema, Eczema, CMK389
Brief summary
The main purpose of this phase 2 study was to assess the efficacy and safety of CMK389 in patients with atopic dermatitis.
Detailed description
This was a randomized, placebo-controlled, parallel-group, non-confirmatory, investigator and participant blinded study in adult participants with moderate to severe AD. The study consisted of up to 4 weeks screening period to assess participants eligibility, the baseline visit, 4-weekly administrations of CMK389 within the first 12 weeks of the 16-week treatment period, and an approximately 12 weeks follow up period which finished with the end of study visit (EoS). In addition, for women of child-bearing potential, pregnancy tests were done for 6 months after the last dose of CMK389.
Interventions
BIOLOGICALCMK389
Active
BIOLOGICALPlacebo
Placebo Comparator
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female participants with chronic atopic dermatitis, aged 18 to 65 years, present for at least 1 year before screening. * Participants with Moderate to severe AD defined by IGA score of ≥ 3 (on a scale of 0 to 4, in which 3 is moderate and 4 is severe) at Baseline, EASI score of ≥ 12 at Baseline and Pruritus (NRS) of at least ≥ 3 at Baseline * Participants who are candidates for a systemic therapy, defined as e.g. inadequate response to treatment with topical medications, or for whom topical treatments are otherwise medically inadvisable (e.g. because of important side effects or safety risks, patients with large affected body surface areas) as assessed by the investigator. * Participants must have a body mass index (BMI) at screening within the range of 18 to ≤35 kg/m2.
Exclusion criteria
* Any skin disease that, in the opinion of the investigator, would confound the diagnosis or evaluation of AD disease activity. * Participants taking prohibited medication not completing the wash out period * Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations. * Any active, recent or recurrent systemic or localized infection at screening or prior to first treatment which in the opinion of the investigator immunocompromises the participant and/or places the participant at unacceptable risk for immunomodulatory therapy, such as: * Any acute bacterial, fungal, or viral skin/mucosal infection that has not resolved within 2 weeks prior to first treatment or within 12 months in case of eczema herpeticum. * Clinically infected AD within 4 weeks prior to first treatment. * Any other infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to first treatment. * Tuberculosis (TB), Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C * Any other current or past clinically significant medical condition, including psychiatric condition, which in the Investigator's opinion may interfere with safety of the participant, study objectives or adherence to the protocol. * Participants with confirmed abnormal absolute neutrophil count (ANC) of \<1.5 x 10\^9/L or with thrombocytopenia of \< 75.0 x 10\^9/L at screening and baseline * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. * History of hypersensitivity to any component of the study drug product, or to drugs of similar chemical classes. * History of severe or serious allergy or hypersensitivity reactions, such as anaphylactic shock, asthma, or uncontrolled urticaria. * Pregnant or nursing (lactating) women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Investigator Global Assessment (IGA) Response | Baseline, Week 16 | The Investigator Global assessment (IGA) scale used was vIGA-AD\^TM (Validated Investigator Global Assessment scale for Atopic Dermatitis). The IGA rating scale was used to determine the severity of atopic dermatitis and clinical response to treatment. It reflected a participant's overall disease severity for the whole body based on a 5-point scale. The 5-point scale included: clear, almost clear, mild, moderate, and severe disease. IGA response is defined as clear or almost clear and at least a 2 point-reduction from baseline at week 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs were reported from first dose until the end of the 12 weeks follow up period, up to a max. duration of approx. 197 days. For women of child-bearing potential, pregnancies were reported (if occurred) for up to approx. 268 days after first dose. | Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation. |
Countries
Czechia, France, Germany, Hungary, Poland, Spain
Participant flow
Recruitment details
Participants took part in 18 investigative sites in 6 countries.
Pre-assignment details
There was a screening period of up to 4 weeks to assess participants eligibility.
Participants by arm
| Arm | Count |
|---|---|
| CMK389 10mg/kg i.v. CMK389 10 mg/kg monthly i.v. dose | 34 |
| CMK389 300mg s.c. CMK389 300mg monthly s.c. dose | 17 |
| Placebo i.v. Placebo monthly i.v. dose | 8 |
| Placebo s.c. Placebo monthly s.c. dose | 8 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Randomized but not treated | 4 | 0 | 0 | 0 |
| Overall Study | Subject/Guardian decision | 3 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | CMK389 10mg/kg i.v. | CMK389 300mg s.c. | Placebo i.v. | Placebo s.c. | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 9.86 | 34.1 years STANDARD_DEVIATION 11.35 | 35.3 years STANDARD_DEVIATION 8.86 | 31.9 years STANDARD_DEVIATION 8.53 | 33.8 years STANDARD_DEVIATION 9.83 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 16 Participants | 8 Participants | 8 Participants | 66 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 3 Participants | 2 Participants | 22 Participants |
| Sex: Female, Male Male | 26 Participants | 8 Participants | 5 Participants | 6 Participants | 45 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 17 | 0 / 8 | 0 / 8 | 0 / 16 | 0 / 67 |
| other Total, other adverse events | 20 / 34 | 11 / 17 | 5 / 8 | 8 / 8 | 13 / 16 | 44 / 67 |
| serious Total, serious adverse events | 1 / 34 | 1 / 17 | 0 / 8 | 0 / 8 | 0 / 16 | 2 / 67 |
Outcome results
Primary
Number of Participants With Investigator Global Assessment (IGA) Response
The Investigator Global assessment (IGA) scale used was vIGA-AD\^TM (Validated Investigator Global Assessment scale for Atopic Dermatitis). The IGA rating scale was used to determine the severity of atopic dermatitis and clinical response to treatment. It reflected a participant's overall disease severity for the whole body based on a 5-point scale. The 5-point scale included: clear, almost clear, mild, moderate, and severe disease. IGA response is defined as clear or almost clear and at least a 2 point-reduction from baseline at week 16.
Time frame: Baseline, Week 16
Population: The safety analysis set included all participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMK389 10mg/kg i.v. | Number of Participants With Investigator Global Assessment (IGA) Response | 5 Participants |
| CMK389 300mg s.c. | Number of Participants With Investigator Global Assessment (IGA) Response | 2 Participants |
| Placebo i.v. | Number of Participants With Investigator Global Assessment (IGA) Response | 0 Participants |
| Placebo s.c. | Number of Participants With Investigator Global Assessment (IGA) Response | 0 Participants |
| Pooled Placebo | Number of Participants With Investigator Global Assessment (IGA) Response | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
Time frame: AEs were reported from first dose until the end of the 12 weeks follow up period, up to a max. duration of approx. 197 days. For women of child-bearing potential, pregnancies were reported (if occurred) for up to approx. 268 days after first dose.
Population: The safety analysis set included all participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMK389 10mg/kg i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 25 Participants |
| CMK389 10mg/kg i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 1 Participants |
| CMK389 10mg/kg i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to discontinuation of study treatment | 0 Participants |
| CMK389 10mg/kg i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to discontinuation of study treatment | 0 Participants |
| CMK389 300mg s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 1 Participants |
| CMK389 300mg s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to discontinuation of study treatment | 0 Participants |
| CMK389 300mg s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to discontinuation of study treatment | 0 Participants |
| CMK389 300mg s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 11 Participants |
| Placebo i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to discontinuation of study treatment | 0 Participants |
| Placebo i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |
| Placebo i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to discontinuation of study treatment | 0 Participants |
| Placebo i.v. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 5 Participants |
| Placebo s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to discontinuation of study treatment | 0 Participants |
| Placebo s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |
| Placebo s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 8 Participants |
| Placebo s.c. | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to discontinuation of study treatment | 0 Participants |