Atopic Dermatitis
Conditions
Brief summary
To investigate the safety and tolerability of repeated subcutaneous (s.c.) doses of MOR106 administered concomitantly with topical corticosteroids (TCS) in participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.
Interventions
DRUGMOR106
MOR106 liquid formulation for s.c. injection administered concomitantly with TCS (medium potency).
DRUGPlacebo
Placebo liquid formulation for s.c. injection administered concomitantly with TCS (medium potency).
Sponsors
Galapagos NV
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 65 Years
Healthy volunteers
No
Inclusion criteria
* A BMI 18 - 40 kilogram per meter square (kg/m\^2), inclusive. * Diagnosis of atopic dermatitis for at least one year since first diagnosis as per the Hanifin and Rajka Criteria. * Eczema Area and Severity Index (EASI) ≥ 16 at the screening and at the baseline visit (Day 1 predose). * Investigators' Global Assessment (IGA) score ≥ 3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and baseline visits. * Greater than or equal to 10% body surface area (BSA) of AD involvement at the screening and baseline visits. * Willingness to use a non-medicated, simple bland emollient twice daily for at least 7 days before the baseline visit and throughout the study.
Exclusion criteria
* Prior treatment with MOR106. * Known hypersensitivity to any investigational medicinal product (IMP) ingredients as determined by the investigator (such as, but not limited to, anaphylaxis requiring hospitalization). * AD lesions located predominantly (≥ 50% of cumulative lesional area) on face and genital areas. * Any concurrent illness, condition, disability, or clinically significant abnormality (including laboratory tests, a New York Heart Association Classification (NYHA) ≥ III/IV) or clinically significant illness in the 3 months prior to initial IMP administration that, in the investigator's opinion, represents a safety risk for the participant's participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the participant from safely completing the assessments required by the protocol. * Clinically significant abnormalities at the discretion of the investigator detected on vital signs or physical examination (other than AD) at screening or baseline (Day 1 predose). * History of or a current immunosuppressive condition (e.g. human immunodeficiency virus \[HIV\] infection, as determined by a positive HIV test at screening). * Active chronic or acute skin infection requiring treatment with systemic (oral, sc or iv) antibiotics, antivirals or antifungals within 4 weeks of baseline, or clinical signs of infective eczema within 7 days before baseline (Day 1 pre-dose). * Having used any of the following treatments: * Prior exposure to Dupilumab. * Immunosuppressive/immunomodulating drugs (e.g. systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-γ, azathioprine, methotrexate) within 4 weeks of baseline (Day 1) visit. * Phototherapy (ultraviolet B \[UVB\] or Psoralen Ultraviolet A \[PUVA\]) for AD within four weeks of baseline (Day 1) visit. * Treatment with TCS or topical calcineurin inhibitor (TCI) within 7 days before the baseline (Day 1) visit. * Treatment with biologics within five half-lives (if known) or 12 weeks prior to baseline visit, whichever is longer. * Regular use (more than two visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | Day 1 up to Day 169/Early discontinuation(ED) | An Adverse Events (AE) was any untoward medical occurrence, new or worsening of any pre-existing condition, in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. TEAEs: AES with an onset date on or after the start date of the IMP administration. AESIs: skin-related events (SRE) (except exacerbation and infective exacerbation of AD) or injection site reactions (ISRs) as per common terminology criteria for AEs (Grade 3: ulceration or necrosis; severe tissue damage; operative intervention indicated, Grade 4: life-threatening consequences; urgent intervention indicated, Grade 5: death ). An SAE: AE that resulted in any of the following outcomes: death; life threatening; results in persistent or significant disability/incapacity; requires in-patient hospitalization or prolongation of existing hospitalization; congenital anomaly/birth defect; is medically significant. |
Secondary
| Measure | Time frame |
|---|---|
| Serum Concentrations of MOR106 | Day 1, Day 4, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141, Day 155 and Day 169 |
| Number of Participants With Anti-drug Antibodies (ADAs) | Day 1 up to Day 169/ED |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 25 Mar 2019. The last study visit occurred on 27 Feb 2020.
Pre-assignment details
A total of 76 participants were screened of which 33 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received MOR106 matching placebo via s.c. injection every other week on Day 1, 15, 29 and 43 given concomitantly with medium potency TCS once daily until Day 57. | 11 |
| MOR106 320 mg Participants received MOR106 320 mg via s.c. injection every other week on Day 15, 29 and 43 given concomitantly with a medium potency TCS once daily until Day 57. A loading dose of MOR106 2 x 320 mg via s.c. injection was administered on Day 1. | 22 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study terminated by sponsor | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 8 |
Baseline characteristics
| Characteristic | MOR106 320 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 36.1 years STANDARD_DEVIATION 13.34 | 37.4 years STANDARD_DEVIATION 14.82 | 39.8 years STANDARD_DEVIATION 17.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 16 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 17 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 24 Participants | 9 Participants |
| Sex: Female, Male Female | 11 Participants | 18 Participants | 7 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 22 |
| other Total, other adverse events | 5 / 11 | 11 / 22 |
| serious Total, serious adverse events | 0 / 11 | 1 / 22 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs)
An Adverse Events (AE) was any untoward medical occurrence, new or worsening of any pre-existing condition, in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. TEAEs: AES with an onset date on or after the start date of the IMP administration. AESIs: skin-related events (SRE) (except exacerbation and infective exacerbation of AD) or injection site reactions (ISRs) as per common terminology criteria for AEs (Grade 3: ulceration or necrosis; severe tissue damage; operative intervention indicated, Grade 4: life-threatening consequences; urgent intervention indicated, Grade 5: death ). An SAE: AE that resulted in any of the following outcomes: death; life threatening; results in persistent or significant disability/incapacity; requires in-patient hospitalization or prolongation of existing hospitalization; congenital anomaly/birth defect; is medically significant.
Time frame: Day 1 up to Day 169/Early discontinuation(ED)
Population: The safety analysis set included all participants who received at least one dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | TEAE | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | AESI: SRE | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | AESI: ISRs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | SAE | 0 Participants |
| MOR106 320 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | SAE | 1 Participants |
| MOR106 320 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | TEAE | 11 Participants |
| MOR106 320 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | AESI: ISRs | 0 Participants |
| MOR106 320 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs) | AESI: SRE | 1 Participants |
Secondary
Number of Participants With Anti-drug Antibodies (ADAs)
Time frame: Day 1 up to Day 169/ED
Population: Safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Anti-drug Antibodies (ADAs) | 0 Participants |
| MOR106 320 mg | Number of Participants With Anti-drug Antibodies (ADAs) | 0 Participants |
Secondary
Serum Concentrations of MOR106
Time frame: Day 1, Day 4, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141, Day 155 and Day 169
Population: The pharmacokinetic (PK) analysis population was a subset of safety analysis set and included all participants who had available and evaluable serum concentration data. Participants in PK population with available data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentrations of MOR106 | Day 1 | 0.149 microgram per milliliter (µg/mL) | Standard Deviation 0.2505 |
| Placebo | Serum Concentrations of MOR106 | Day 4 | 61.150 microgram per milliliter (µg/mL) | Standard Deviation 28.385 |
| Placebo | Serum Concentrations of MOR106 | Day 15 | 41.278 microgram per milliliter (µg/mL) | Standard Deviation 21.4046 |
| Placebo | Serum Concentrations of MOR106 | Day 29 | 39.473 microgram per milliliter (µg/mL) | Standard Deviation 15.8087 |
| Placebo | Serum Concentrations of MOR106 | Day 43 | 42.537 microgram per milliliter (µg/mL) | Standard Deviation 23.8095 |
| Placebo | Serum Concentrations of MOR106 | Day 57 | 40.934 microgram per milliliter (µg/mL) | Standard Deviation 17.6737 |
| Placebo | Serum Concentrations of MOR106 | Day 71 | 16.593 microgram per milliliter (µg/mL) | Standard Deviation 7.3308 |
| Placebo | Serum Concentrations of MOR106 | Day 85 | 9.775 microgram per milliliter (µg/mL) | Standard Deviation 3.2489 |
| Placebo | Serum Concentrations of MOR106 | Day 99 | 5.092 microgram per milliliter (µg/mL) | Standard Deviation 1.0801 |
| Placebo | Serum Concentrations of MOR106 | Day 113 | 2.415 microgram per milliliter (µg/mL) | Standard Deviation 1.3466 |
| Placebo | Serum Concentrations of MOR106 | Day 127 | 1.407 microgram per milliliter (µg/mL) | Standard Deviation 0.8124 |
| Placebo | Serum Concentrations of MOR106 | Day 141 | 1.812 microgram per milliliter (µg/mL) | Standard Deviation 2.4765 |
| Placebo | Serum Concentrations of MOR106 | Day 155 | 1.043 microgram per milliliter (µg/mL) | Standard Deviation 1.2149 |
| Placebo | Serum Concentrations of MOR106 | Day 169 | 0.690 microgram per milliliter (µg/mL) | Standard Deviation 0.9707 |