A 4 Week Study of the Safety, Tolerability, and Pharmacodynamics of ShK-186 (Dalazatide) in Active Plaque Psoriasis

A 4 Week Study of the Safety, Tolerability, and Pharmacodynamics of ShK-186 in Active Plaque Psoriasis

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.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: dalazatide; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 30ug dalazatide; 12 subjects, 10 given active agent and 2 given placebo by subcutaneous injection twice weekly for 4 weeks.	Drug: dalazatide; Subcutaneous injection twice per week for a total of 9 doses, followed by four weeks of follow-up.; Other Names: ShK-186; Drug: placebo; placebo, Subcutaneous injection twice per week for a total of 9 doses
Experimental: 60ug dalazatide; 12 subjects, 10 given active agent and 2 given placebo by subcutaneous injection twice weekly for 4 weeks.	Drug: dalazatide; Subcutaneous injection twice per week for a total of 9 doses, followed by four weeks of follow-up.; Other Names: ShK-186; Drug: placebo; placebo, Subcutaneous injection twice per week for a total of 9 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Subjects with adverse events	From randomization through Day 57 (12 timepoints)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion assessment	Target lesion evaluated for erythema, induration, and scaling.	From randomization to Day 57 (4 timepoints)
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	Skin biopsy from psoriatic lesion collected for analysis of gene expression via qPCR and immune cell infiltration via histology and immunohistochemistry analysis.	From randomaization to Day 32 (2 timepoints)
Blood biomarker assessments	Blood collected for analysis of gene and protein expression as well as immunophenotyping of T cell subsets.	From randomizatoin to Day 57 (5 timepoints)
Dermatology Quality of Life Questionnaire (DLQI)		From randomization to Day 57 (4 timepoints)
Presence of specific anti-drug antibodies to dalazatide	Serum evaluated for specific anti-drug antibody using ELISA-based immunoassay.	From randomization to Day 57 (three timepoints)
Subjects with changes in vital signs	Vital signs include temperature, respiratory rate, supine blood pressure and pulse.	From randomization to Day 57 (12 timepoints)
Subjects with changes in symptom-directed physical examinations		From randomization to day 5 (12 timepoints)

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Kineta Inc.
• Investigators: Study Director: Shawn Iadonato, PhD, Kineta Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Estimate): May 6, 2015
• Last Update Submitted That Met QC Criteria: May 1, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: psoriasis; autoimmune; ShK-186; dalazatide; Kv1.3,
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 186-03