To explore the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of LOU064 over a treatment period of 4 weeks in a cohort of subjects with atopic dermatitis.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety assessments:
Adverse events
Physical examination and anamnesis including a bruising log
Test for occult blood in stool and urine
Laboratory assessments including standard coagulation tests and platelets
Vital signs
ECG
Secondary outcome
PK: Cmax, Tmax, AUClast, AUCinf, T1/2, Vz/F and CL/F from the blood
concentration-time data.
PD: BTK occupancy in whole blood, ex-vivo anti-IgE activation of Basophils
(Basotest) and skin prick test to a known allergen.
Dermatology assessments to determine the potential effectiveness of LOU064 on
skin symptoms in AD.
Background summary
LOU064 is a selective covalent irreversible inhibitor of BTK and among a new
generation of designed covalent enzyme inhibitors. The immunomodulatory action
of LOU064 is mediated by its inhibition of BTK in the targeted pathways (e.g.
mast cell and basophils degranulation via Fc*R) Atopic dermatitis (AD) is a
common chronic, relapsing inflammatory, itchy skin disease affecting children
and adult with a lifetime prevalence of 10*20% in children, and 1*3% in adults.
It is thought to be caused by a variety of factors including genetic,
environmental, and immunologic factors. Often AD is classified as intrinsic (or
*non-allergic*) with low or normal IgE levels or the more frequent extrinsic
(or *allergic*) AD which is characterized by high or very high IgE levels.
Exposure to allergens, either from food or the environment, such as dust mites
or pollens, can trigger flares in many AD patients and IgE levels are thought
to be correlated to the disease severity. Blocking BTK downstream from the
intracellular Fc*R-pathway triggered by the interaction with IgE may be a
reliable therapeutic approach for diseases where IgE play a role.
Study objective
To explore the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics
(PD) of LOU064 over a treatment period of 4 weeks in a cohort of subjects with
atopic dermatitis.
Study design
Part 6 is a double-blind, placebo-controlled multiple dose study in subjects
with atopic dermatitis with a 4-week treatment period (twice daily dosing of
LOU064 100mg) and 3-week follow-up period in 16 subjects.
Intervention
100mg LOU064 or matching placebo BID
Study burden and risks
Testing a cohort of subjects with a disease that is potentially addressed by
LOU064 is of particular interest because it is relevant to assess the impact of
influencing the target in a patient population and whether this may have an
influence on the PK and PD
parameters different from those in healthy volunteers. Also, given the
accumulated safety data in doses up to 6-fold the single and 3-fold the daily
dose for 12 days, the risk for toxicity in this population is low.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female healthy subjects with an age range between 18 and 65 years (inclusive), and in good general health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. To participate in Part 6, subjects must additionally have chronic atopic dermatitis (AD) according to American Academy of Dermatology Consensus Criteria (Eichenfield et al 2014), that has been present for at least 1 year before the baseline visit and defined as:
* Eczema Area and Severity Index (EASI) * 12 at screening and baseline
* IGA (Investigator*s Global Assessment) * 3 on a 5-point scale at screening and baseline
* BSA (Body Surface Area) involvement * 8% at screening and baseline
* Subjects have applied a stable dose of bland topical emollient at least twice daily for at least 7 consecutive days immediately before the baseline visit
Subjects must weigh at least 50 kg and must have a body mass index (BMI) within the range of 18 18-35 kg/m2 inclusive (part 6).
Exclusion criteria
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
7. Use of any systemic prescription drugs (including CYP3A inducers and inhibitors, and drugs with arrhythmogenic potential)
9. 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 hCG laboratory test
16. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
18. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
19. A positive Hepatitis B test result (Hepatitis B surface antigen/Hepatitis B core antibody) or Hepatitis C test result.
20. Subjects with a latent TB infection as indicated by the absence of any signs of active TB disease but with a positive IGRA.
36. Subjects previously enrolled and dosed in any part of this study are not eligible to re-enroll in the same or another part.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003750-40-NL |
| CCMO | NL68204.056.18 |