Plaque Psoriasis
Conditions
Keywords
ShK-186, dalazatide, psoriasis, Kv1.3,, autoimmune
Brief summary
The primary purpose of this study is to examine safety outcomes in active plaque psoriasis patients after systemic administration of dalazatide. Clinical outcome measures will also be assessed.
Detailed description
The primary purpose of this study is to examine safety outcomes in active plaque psoriasis patients after systemic administration of dalazatide. Clinical outcome measures will also be assessed.
Interventions
DRUGdalazatide
Subcutaneous injection twice per week for a total of 9 doses, followed by four weeks of follow-up.
DRUGplacebo
placebo, Subcutaneous injection twice per week for a total of 9 doses
Sponsors
Kineta Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adult male and female subjects, ages 18-65; 2. Active plaque psoriasis with ≥3% BSA involved; 3. An adequate number of vulgar psoriatic plaques of at least 2 cm X 2 cm with Target Lesion Investigator Global Assessment scores \>3, that are not located on the face, scalp, groin, genitals, folds, palms or soles 4. Weight of 50 - 100 kg; 5. Non-child bearing potential or willingness to use adequate contraception in order to prevent pregnancy from the screening visit until 60 days after the follow-up visit. 6. Subject will be evaluated for latent TB infection. 7. Able to communicate and able to provide valid, written informed consent;
Exclusion criteria
The following will exclude potential subjects from the study: 1. Erythrodermic, predominantly guttate, exclusively palmar/plantar, or generalized pustular psoriasis; 2. Current drug-induced or aggravated psoriasis (e.g., a new onset of psoriasis or an exacerbation of psoriasis from beta-blockers, calcium-channel blockers, or lithium carbonate); 3. Use of the following concurrent systemic medications: corticosteroids, retinoids, cyclosporine, methotrexate, or biologic agents. 4. Use of concurrent topical medications (must be discontinued at least 2 weeks prior to baseline); 5. UVA or UVB therapy within 4 weeks of baseline; 6. The presence of uncontrolled hypertension, uncontrolled diabetes, clinically significant cardiovascular disease, asthma or reduced pulmonary capacity, or a history of seizure or other neurologic disorder; 7. Presence or history of pre-existing paresthesia or neuropathy; 8. Abnormalities on neurological exam at screening or baseline; 9. Clinically significant ECG abnormalities, in the opinion of the Investigator; 10. History of any cancer requiring systemic chemotherapy or radiation; 11. The presence of acute infection or history of acute infection as judged by the Investigator within 7 days of baseline; 12. The presence of clinically significant laboratory abnormalities; 13. A positive hepatitis screen (Hepatitis BsAg or anti-HCV) or positive Human Immunodeficiency Virus (HIV) antibody test ; 14. History of treated or untreated TB 15. Any history of anaphylaxis that is important in the view of the Investigator; 16. Participation in another clinical trial with receipt of an investigational product within 90 days of baseline (or 5 half-lives of the previous drug, whichever is longer); 17. History of alcohol abuse that is important in the view of the Investigator; 18. Positive drug screen for amphetamines, barbituates, benzodiazepines, cocaine, cannabis, methamphetamine, methylenedioxymethanphetamine, opiates or phencyclidine 19. Inadequate venous access that would interfere with obtaining blood samples; 20. Positive pregnancy test at screening or at baseline or current lactation (female subjects only); 21. Inability or unwillingness to comply with study restrictions, return for follow up appointments, or other considerations, in the opinion of the Investigator, which would make the candidate unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Subjects with adverse events | From randomization through Day 57 (12 timepoints) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target lesion assessment | From randomization to Day 57 (4 timepoints) | Target lesion evaluated for erythema, induration, and scaling. |
| Psoriasis Area Severity Index (PASI) score | From randomization to Day 57 (4 timepoints) | — |
| Patient and Investigator Global Assessment of Psoriasis | From randomization to Day 57 (4 timepoints) | — |
| Psoriasis Disability Index (PDI) | From randomization to Day 57 (4 timepoints) | — |
| Skin biomarker assessments | From randomaization to Day 32 (2 timepoints) | Skin biopsy from psoriatic lesion collected for analysis of gene expression via qPCR and immune cell infiltration via histology and immunohistochemistry analysis. |
| Dermatology Quality of Life Questionnaire (DLQI) | From randomization to Day 57 (4 timepoints) | — |
| Presence of specific anti-drug antibodies to dalazatide | From randomization to Day 57 (three timepoints) | Serum evaluated for specific anti-drug antibody using ELISA-based immunoassay. |
| Subjects with changes in vital signs | From randomization to Day 57 (12 timepoints) | Vital signs include temperature, respiratory rate, supine blood pressure and pulse. |
| Subjects with changes in symptom-directed physical examinations | From randomization to day 5 (12 timepoints) | — |
| Blood biomarker assessments | From randomizatoin to Day 57 (5 timepoints) | Blood collected for analysis of gene and protein expression as well as immunophenotyping of T cell subsets. |
Other
| Measure | Time frame |
|---|---|
| Area under the plasma concentration versus time curve of dalazatide (AUC) | 5 minutes pose dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 4 hours post dose |
Countries
Canada
Outcome results
None listed