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

Primary Purpose

Hidradenitis Suppurativa, Palmoplantar Pustulosis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hidradenitis Suppurativa

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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."

Sites / Locations

  • Holdsworth House Medical Practice
  • Fremantle Dermatology
  • The Royal Melbourne Hospital
  • Westmead Hospital
  • Bispebjerg Hospital
  • Gentofte Hospital
  • Zealand University Hospital
  • Charité - Universitätsmedizin Berlin
  • St. Josef Hospital
  • Klinikum Darmstadt
  • Universitätsklinikum Carl Gustav Carus

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Level 1 (HS)

Dose Level 1 (PPP)

Dose Level 1 (Total)

Dose Level 2 (HS)

Dose Level 2 (PPP)

Dose Level 2 (Total)

Arm Description

Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS

Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP

Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP

Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS

Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP

Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs)
TEAEs by severity
TEAEs by casuality
Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia
AESIs: Grade 3 and 4 neutropenia by causality
Incidence of AESIs: Grade 3 and 4 infection
AESIs: Grade 3 and 4 infection by causality

Secondary Outcome Measures

Maximum concentration (Cmax) of CSL324 in serum for the first dose administered
Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered
Area under the concentration-time curve during a dosing interval (AUCtau) of CSL324 in serum for the first dose administered
Cmax of CSL324 in serum for the last dose administered
Tmax of CSL324 in serum for the last dose administered
AUCtau of CSL324 in serum for the last dose administered
Half life (t½) of CSL324 in serum for the last dose administered
Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered
Volume of distribution after intravenous dosing during the terminal elimination phase ( Vz) of CSL324 in serum for the last dose administered
Ctrough of CSL324 for each dose of CSL324 administered
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)
Presence of anti-CSL324 antibodies in serum

Full Information

First Posted
May 31, 2019
Last Updated
May 25, 2023
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT03972280
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 4, 2019 (Actual)
Primary Completion Date
October 4, 2022 (Actual)
Study Completion Date
October 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hidradenitis Suppurativa, Palmoplantar Pustulosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1 (HS)
Arm Type
Experimental
Arm Description
Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS
Arm Title
Dose Level 1 (PPP)
Arm Type
Experimental
Arm Description
Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
Arm Title
Dose Level 1 (Total)
Arm Type
Experimental
Arm Description
Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
Arm Title
Dose Level 2 (HS)
Arm Type
Experimental
Arm Description
Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS
Arm Title
Dose Level 2 (PPP)
Arm Type
Experimental
Arm Description
Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
Arm Title
Dose Level 2 (Total)
Arm Type
Experimental
Arm Description
Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
Intervention Type
Biological
Intervention Name(s)
Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
Other Intervention Name(s)
CSL324
Intervention Description
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame
Up to 24 weeks
Title
TEAEs by severity
Time Frame
Up to 24 weeks
Title
TEAEs by casuality
Time Frame
Up to 24 weeks
Title
Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia
Time Frame
Up to 24 weeks
Title
AESIs: Grade 3 and 4 neutropenia by causality
Time Frame
Up to 24 weeks
Title
Incidence of AESIs: Grade 3 and 4 infection
Time Frame
Up to 24 weeks
Title
AESIs: Grade 3 and 4 infection by causality
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Maximum concentration (Cmax) of CSL324 in serum for the first dose administered
Time Frame
Up to 22 days after dose
Title
Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered
Time Frame
Up to 22 days after dose
Title
Area under the concentration-time curve during a dosing interval (AUCtau) of CSL324 in serum for the first dose administered
Time Frame
Up to 22 days after dose
Title
Cmax of CSL324 in serum for the last dose administered
Time Frame
Up to 22 days after dose
Title
Tmax of CSL324 in serum for the last dose administered
Time Frame
Up to 84 days after dose
Title
AUCtau of CSL324 in serum for the last dose administered
Time Frame
Up to 22 days after dose
Title
Half life (t½) of CSL324 in serum for the last dose administered
Time Frame
Up to 84 days after dose
Title
Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered
Time Frame
Up to 22 days after dose
Title
Volume of distribution after intravenous dosing during the terminal elimination phase ( Vz) of CSL324 in serum for the last dose administered
Time Frame
Up to 22 days after dose
Title
Ctrough of CSL324 for each dose of CSL324 administered
Time Frame
Up to 22 days after each dose
Title
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)
Time Frame
Up to 22 days after each dose
Title
Presence of anti-CSL324 antibodies in serum
Time Frame
Up to 168 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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."
Facility Information:
Facility Name
Holdsworth House Medical Practice
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
Fremantle Dermatology
City
Fremantle
ZIP/Postal Code
6160
Country
Australia
Facility Name
The Royal Melbourne Hospital
City
Parkville
ZIP/Postal Code
3052
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
ZIP/Postal Code
2145
Country
Australia
Facility Name
Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Gentofte Hospital
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Facility Name
Zealand University Hospital
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
St. Josef Hospital
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Klinikum Darmstadt
City
Darmstadt
ZIP/Postal Code
64283
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
IPD Sharing Time Frame
IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
IPD Sharing Access Criteria
Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

Learn more about this trial

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

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