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

Phase 1

Completed

• Conditions: Hidradenitis Suppurativa; Palmoplantar Pustulosis
• Interventions: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody

• Registration Number: NCT03972280
• Lead Sponsor: CSL Behring

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-31
• Study First Submitted QC: 2019-05-31
• Study First Posted: 2019-06-03
• Study Start: 2019-07-04
• Primary Completion: 2022-10-04
• Study Completion: 2022-10-04
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-25
• Last Update Posted: 2023-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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

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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."

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level 1 (PPP)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
Dose Level 2 (PPP)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
Dose Level 2 (Total)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
Dose Level 1 (HS)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS
Dose Level 1 (Total)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
Dose Level 2 (HS)	Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody	Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS

Primary Outcome Measures

Name	Time	Method
AESIs: Grade 3 and 4 neutropenia by causality	Up to 24 weeks
AESIs: Grade 3 and 4 infection by causality	Up to 24 weeks
Incidence of treatment-emergent adverse events (TEAEs)	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
TEAEs by severity	Up to 24 weeks
Incidence of AESIs: Grade 3 and 4 infection	Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Cmax of CSL324 in serum for the last dose administered	Up to 22 days after dose
Maximum concentration (Cmax) of CSL324 in serum for the first 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
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
Total systemic clearance (CLtot) after intravenous dosing 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
Half life (t½) of CSL324 in serum for the last dose administered	Up to 84 days after 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
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

Trial Locations

Locations (11)

Holdsworth House Medical Practice; 🇦🇺 Darlinghurst, Australia

Fremantle Dermatology; 🇦🇺 Fremantle, Australia

Westmead Hospital; 🇦🇺 Westmead, Australia

St. Josef Hospital; 🇩🇪 Bochum, Germany

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Bispebjerg Hospital; 🇩🇰 Copenhagen, Denmark

Gentofte Hospital; 🇩🇰 Hellerup, Denmark

Zealand University Hospital; 🇩🇰 Roskilde, Denmark

Klinikum Darmstadt; 🇩🇪 Darmstadt, Germany

The Royal Melbourne Hospital; 🇦🇺 Parkville, Australia