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出境医 / 临床实验 / Safety and Pharmacokinetics of Repeat Doses of CSL324 in Subjects With Hidradenitis Suppurativa and Palmoplantar Pustulosis

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

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.

Condition or disease Intervention/treatment Phase
Hidradenitis Suppurativa Palmoplantar Pustulosis Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Dose Level 1 (HS)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Experimental: Dose Level 1 (PPP)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Experimental: Dose Level 1 (Total)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Experimental: Dose Level 2 (HS)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Experimental: Dose Level 2 (PPP)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Experimental: Dose Level 2 (Total)
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
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Outcome Measures
Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 24 weeks ]
  2. TEAEs by severity [ Time Frame: Up to 24 weeks ]
  3. TEAEs by casuality [ Time Frame: Up to 24 weeks ]
  4. Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia [ Time Frame: Up to 24 weeks ]
  5. AESIs: Grade 3 and 4 neutropenia by causality [ Time Frame: Up to 24 weeks ]
  6. Incidence of AESIs: Grade 3 and 4 infection [ Time Frame: Up to 24 weeks ]
  7. AESIs: Grade 3 and 4 infection by causality [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :
  1. Maximum concentration (Cmax) of CSL324 in serum for the first dose administered [ Time Frame: Up to 22 days after dose ]
  2. Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered [ Time Frame: Up to 22 days after dose ]
  3. 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 ]
  4. Cmax of CSL324 in serum for the last dose administered [ Time Frame: Up to 22 days after dose ]
  5. Tmax of CSL324 in serum for the last dose administered [ Time Frame: Up to 84 days after dose ]
  6. AUCtau of CSL324 in serum for the last dose administered [ Time Frame: Up to 22 days after dose ]
  7. Half life (t½) of CSL324 in serum for the last dose administered [ Time Frame: Up to 84 days after dose ]
  8. Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered [ Time Frame: Up to 22 days after dose ]
  9. 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 ]
  10. Ctrough of CSL324 for each dose of CSL324 administered [ Time Frame: Up to 22 days after each dose ]
  11. 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 ]
  12. Presence of anti-CSL324 antibodies in serum [ Time Frame: Up to 168 days ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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."
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Trial Register Coordinator 610-878-4000 clinicaltrials@cslbehring.com

Locations
Layout table for location information
Australia
Holdsworth House Medical Practice Recruiting
Darlinghurst, Australia, 2010
Contact: Use Central Contact         
Fremantle Dermatology Recruiting
Fremantle, Australia, 6160
Contact: Use Central Contact         
The Royal Melbourne Hospital Recruiting
Parkville, Australia, 3052
Contact: Use Central Contact         
Westmead Hospital Recruiting
Westmead, Australia, 2145
Contact: Use Central Contact         
Denmark
Bispebjerg Hospital Recruiting
Copenhagen, Denmark, 2400
Contact: Use Central Contact         
Gentofte Hospital Recruiting
Hellerup, Denmark, 2900
Contact: Use Central Contact         
Zealand University Hospital Recruiting
Roskilde, Denmark, 4000
Contact: Use Central Contact         
Germany
Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Use Central Contact         
St. Josef Hospital Recruiting
Bochum, Germany, 44791
Contact: Use Central Contact         
Klinikum Darmstadt Recruiting
Darmstadt, Germany, 64283
Contact: Use Central Contact         
Universitätsklinikum Carl Gustav Carus Recruiting
Dresden, Germany, 01307
Contact: Use Central Contact         
Technische Universität München Recruiting
Mücheln, Germany, 80802
Contact: Use Central Contact         
Sponsors and Collaborators
CSL Behring
Tracking Information
First Submitted Date  ICMJE May 31, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date May 20, 2021
Actual Study Start Date  ICMJE July 4, 2019
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 24 weeks ]
  • TEAEs by severity [ Time Frame: Up to 24 weeks ]
  • TEAEs by casuality [ Time Frame: Up to 24 weeks ]
  • Incidence of adverse events of special interest (AESIs): Grade 3 and 4 neutropenia [ Time Frame: Up to 24 weeks ]
  • AESIs: Grade 3 and 4 neutropenia by causality [ Time Frame: Up to 24 weeks ]
  • Incidence of AESIs: Grade 3 and 4 infection [ Time Frame: Up to 24 weeks ]
  • AESIs: Grade 3 and 4 infection by causality [ Time Frame: Up to 24 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Maximum concentration (Cmax) of CSL324 in serum for the first dose administered [ Time Frame: Up to 22 days after dose ]
  • Time to maximum concentration (Tmax) of CSL324 in serum for the first dose administered [ Time Frame: 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 [ Time Frame: Up to 22 days after dose ]
  • Cmax of CSL324 in serum for the last dose administered [ Time Frame: Up to 22 days after dose ]
  • Tmax of CSL324 in serum for the last dose administered [ Time Frame: Up to 84 days after dose ]
  • AUCtau of CSL324 in serum for the last dose administered [ Time Frame: Up to 22 days after dose ]
  • Half life (t½) of CSL324 in serum for the last dose administered [ Time Frame: Up to 84 days after dose ]
  • Total systemic clearance (CLtot) after intravenous dosing of CSL324 in serum for the last dose administered [ Time Frame: 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 [ Time Frame: Up to 22 days after dose ]
  • Ctrough of CSL324 for each dose of CSL324 administered [ Time Frame: 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) [ Time Frame: Up to 22 days after each dose ]
  • Presence of anti-CSL324 antibodies in serum [ Time Frame: Up to 168 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacokinetics of Repeat Doses of CSL324 in Subjects With Hidradenitis Suppurativa and Palmoplantar Pustulosis
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hidradenitis Suppurativa
  • Palmoplantar Pustulosis
Intervention  ICMJE Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
Recombinant anti-G-CSF receptor monoclonal antibody is a preservative-free, sterile liquid formulation that is suitable for intravenous infusion
Other Name: CSL324
Study Arms  ICMJE
  • Experimental: Dose Level 1 (HS)
    Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
  • Experimental: Dose Level 1 (PPP)
    Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
  • Experimental: Dose Level 1 (Total)
    Dose 1 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
  • Experimental: Dose Level 2 (HS)
    Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
  • Experimental: Dose Level 2 (PPP)
    Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with PPP
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
  • Experimental: Dose Level 2 (Total)
    Dose 2 of recombinant anti-G-CSF receptor monoclonal antibody administered intravenously to subjects with HS or PPP
    Intervention: Biological: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 31, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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."
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Register Coordinator 610-878-4000 clinicaltrials@cslbehring.com
Listed Location Countries  ICMJE Australia,   Denmark,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03972280
Other Study ID Numbers  ICMJE CSL324_1002
2018-002871-17 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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.
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.
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CSL Behring
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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