Clinical trial NCT03972280: Safety and Pharmacokinetics of Repeat Doses of CSL324 in Subjects With Hidradenitis Suppurativa and Palmoplantar Pustulosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hidradenitis Suppurativa
Palmoplantar Pustulosis
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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."

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 24 weeks
measure: TEAEs by severity
timeFrame: Up to 24 weeks
measure: TEAEs by casuality
timeFrame: Up to 24 weeks
measure: Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia
timeFrame: Up to 24 weeks
measure: AESIs: Grade 3 and 4 neutropenia by causality
timeFrame: Up to 24 weeks
measure: Incidence of AESIs: Grade 3 and 4 infection
timeFrame: Up to 24 weeks
measure: AESIs: Grade 3 and 4 infection by causality
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Maximum concentration (Cmax) of CSL324 in serum for the first dose administered
timeFrame: Up to 22 days after dose
measure: Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered
timeFrame: Up to 22 days after dose
measure: Area under the concentration-time curve during a dosing interval (AUCtau) of CSL324 in serum for the first dose administered
timeFrame: Up to 22 days after dose
measure: Cmax of CSL324 in serum for the last dose administered
timeFrame: Up to 22 days after dose
measure: Tmax of CSL324 in serum for the last dose administered
timeFrame: Up to 84 days after dose
measure: AUCtau of CSL324 in serum for the last dose administered
timeFrame: Up to 22 days after dose
measure: Half life (t½) of CSL324 in serum for the last dose administered
timeFrame: Up to 84 days after dose
measure: Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered
timeFrame: Up to 22 days after dose
measure: Volume of distribution after intravenous dosing during the terminal elimination phase ( Vz) of CSL324 in serum for the last dose administered
timeFrame: Up to 22 days after dose
measure: Ctrough of CSL324 for each dose of CSL324 administered
timeFrame: Up to 22 days after each dose
measure: 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)
timeFrame: Up to 22 days after each dose
measure: Presence of anti-CSL324 antibodies in serum
timeFrame: Up to 168 days
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
city: Fremantle
country: Australia
facility: Fremantle Dermatology
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: St. Josef Hospital
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
Study officials:
References: