Safety and Pharmacokinetics of Repeat Doses of CSL324 in Subjects With Hidradenitis Suppurativa and Palmoplantar Pustulosis

Study Overview
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Brief Summary
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Study CSL324_1002 will investigate the safety and pharmacokinetics of repeat doses of CSL324 in subjects with hidradenitis suppurativa and palmoplantar pustulosis. CSL324 is a novel, recombinant therapy that may treat diseases caused by increased numbers of neutrophils at sites of inflammation.

Official Title
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A Multicenter, Open-label, 2-regimen, Repeat-dose Study to Assess the Safety and Pharmacokinetics of Intravenous CSL324 in Subjects With Hidradenitis Suppurativa and Palmoplantar Pustulosis

Conditions
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Hidradenitis Suppurativa, Palmoplantar Pustulosis

Intervention / Treatment
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* Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18 and 75 years of age, inclusive Confirmed clinical diagnosis of moderate to severe HS as per International Hidradenitis Suppurativa Severity Score System (IHS4) guidelines (ie, IHS4 ≥ 4) PPP differentiated from other forms of pustulosis Psoriasis with a Palmoplantar Pustulosis Psoriasis Area and Severity Index (ppPASI) score of ≥ 12. Subjects with HS only: inadequate response to at least a 3-month (90 days) trial of oral antibiotics for treatment of HS Subjects with PPP only: confirmed clinical diagnosis of PPP at least 6 months before Screening and inadequate response to topical therapy, phototherapy, and / or previous systemic therapy for the treatment of PPP Exclusion Criteria: Treatment with any medications and therapies not permitted during the study. History of myeloproliferative disease. Malignancy within 5 years at Screening with the exception of nonmelanoma skin cancer, carcinoma in situ, or prostate cancer not requiring treatment. Current, or a recent clinically significant history of, uncontrolled renal, hepatic(including currently active hepatitis B virus and / or hepatitis C virus), hematologic, endocrine, pulmonary, psychiatric, or cardiac disease, assessed as potentially having an effect on study outcomes as determined by the Investigator and / or Sponsor. Congenital or acquired immunosuppressive condition(s), including human immunodeficiency virus infection. Clinical signs of active infection and / or fever > 38°C during the 7 days before Day 1. Clinically significant abnormalities on physical examination, ECG, or laboratory assessments, or neutropenia (defined as absolute neutrophil count < 2.0 × 109/L) at Screening. Subjects with PPP only: concurrent psoriasis vulgaris (not including scaly scalp and / or ears). Subjects with HS only: > 20 draining fistulas.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1 (HS)<br>Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|
| Experimental: Dose Level 1 (PPP)<br>Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|
| Experimental: Dose Level 1 (Total)<br>Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|
| Experimental: Dose Level 2 (HS)<br>Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|
| Experimental: Dose Level 2 (PPP)<br>Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|
| Experimental: Dose Level 2 (Total)<br>Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP | Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>* Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion<br>* Other names: CSL324;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) |  | Up to 24 weeks | 
| TEAEs by severity |  | Up to 24 weeks | 
| TEAEs by casuality |  | Up to 24 weeks | 
| Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia |  | Up to 24 weeks | 
| AESIs: Grade 3 and 4 neutropenia by causality |  | Up to 24 weeks | 
| Incidence of AESIs: Grade 3 and 4 infection |  | Up to 24 weeks | 
| AESIs: Grade 3 and 4 infection by causality |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of CSL324 in serum for the first dose administered |  | Up to 22 days after dose | 
| Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered |  | Up to 22 days after dose | 
| Area under the concentration-time curve during a dosing interval (AUCtau) of CSL324 in serum for the first dose administered |  | Up to 22 days after dose | 
| Cmax of CSL324 in serum for the last dose administered |  | Up to 22 days after dose | 
| Tmax of CSL324 in serum for the last dose administered |  | Up to 84 days after dose | 
| AUCtau of CSL324 in serum for the last dose administered |  | Up to 22 days after dose | 
| Half life (t½) of CSL324 in serum for the last dose administered |  | Up to 84 days after dose | 
| Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered |  | Up to 22 days after dose | 
| Volume of distribution after intravenous dosing during the terminal elimination phase ( Vz) of CSL324 in serum for the last dose administered |  | Up to 22 days after dose | 
| Ctrough of CSL324 for each dose of CSL324 administered |  | Up to 22 days after each dose | 
| Accumulation ratio for AUCtau (ratio between AUCtau of the last dose and of the first dose) and accumulation ratio for Cmax (ratio between Cmax of the last dose and of the first dose) |  | Up to 22 days after each dose | 
| Presence of anti-CSL324 antibodies in serum |  | Up to 168 days |