Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)
Primary Purpose
Diffuse Cutaneous Systemic Sclerosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IgPro20
IgPro10
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Cutaneous Systemic Sclerosis focused on measuring scleroderma
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years (male or female) at time of providing written informed consent
- Documented diagnosis of systemic sclerosis (scleroderma) according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria 2013 (diffuse cutaneous form of SSc).
- Modified Rodnan Skin Score (mRSS) ≥ 15 and ≤ 45 at screening
- Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
- Capable of providing written informed consent and willing and able to adhere to all protocol requirements
Exclusion Criteria:
- Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, as determined by the investigator. Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy at screening are not excluded
- Subject has mRSS > 2 at the potential subcutaneous (SC) infusion sites
- History of skin condition precluding SC infusion, or clinical signs and symptoms of a chronic skin disease other than systemic sclerosis or skin manifestation of an allergic disease or other dermatological conditions that would interfere with trial assessments or compromise safety (eg, dermatitis, eczema, psoriasis)
- Subject has clinical signs and symptoms of skin irritation (eg, pruritus, burning, erythema) or hypo/ hyperpigmentation (eg, scars, tattoos) at the potential SC infusion sites
- Significant pulmonary arterial hypertension as documented by mean pulmonary arterial pressure > 30 mmHg on right heart catheterization requiring SC or IV prostacyclin or use of dual oral therapies
- Forced vital capacity < 50% predicted or a diffusing capacity of the lung for carbon dioxide (DLCO) ≤ 40% predicted (corrected for hemoglobin)
- A female who is pregnant, breastfeeding, or is a woman of childbearing potential who does not agree to use acceptable methods of contraception; a male who does agree to use acceptable methods of contraception.
- Evidence of chronic kidney disease with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 or if subject is receiving dialysis. Subjects with current confirmed diagnosis of diabetes mellitus requiring medication with an eGFR < 90 ml/min/1.73m2
Sites / Locations
- Royal Adelaide Hospital
- Charité Universitätsmedizin Berlin
- Uniklinik Köln, innere Medizin
- ASST Spedali Civili di Brescia
- Azienda Ospedaliera Gaetano Pini
- Uniwersytecki Szpital Kliniczny W Bialymstoku
- Szpital Kliniczny Jezus
- Narodowy Instytut Geriatrii
- The Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IgPro20
IgPro10
Arm Description
20% liquid formulation of human immunoglobulin for subcutaneous use
10% liquid formulation of human immunoglobulin for intravenous use
Outcomes
Primary Outcome Measures
Number of subjects with adverse events (AEs) for IgPro20
Percentage of subjects with AEs for IgPro20
Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro20
Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro20
Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro20
Number of patients with AEs categorized as infusion site reactions (ISRs) for IgPro20
Percentage of patients with AEs categorized as ISRs for IgPro20
Rate of ISRs per subject for IgPro20
Rate of ISRs per infusion for IgPro20
Onset of ISRs for IgPro20
Duration of ISRs for IgPro20
Secondary Outcome Measures
IgPro20 relative bioavailability (%F)
Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro20
Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro20
Maximum plasma drug concentration (Cmax) for IgPro20
Minimum plasma drug concentration (Ctrough) for IgPro20
Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro10
Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro10
Maximum plasma drug concentration (Cmax) for IgPro10
Minimum plasma drug concentration (Ctrough) for IgPro10
Number and percentage of subjects with AEs for IgPro10
Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro10
Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro10
Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro10
Number and percentage of subjects with AEs categorized as ISRs for IgPro10
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04137224
Brief Title
Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)
Official Title
A Multicenter, Randomized, Open-label, Crossover, Phase 2 Study to Evaluate the Safety and Pharmacokinetics of IgPro20 (Subcutaneous Immunoglobulin, Hizentra®) and IgPro10 (Intravenous Immunoglobulin, Privigen®) in Adults With Systemic Sclerosis (SSc)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 19, 2019 (Actual)
Primary Completion Date
May 17, 2022 (Actual)
Study Completion Date
May 17, 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
This is a prospective, multicenter, randomized, open-label, crossover study to investigate the safety, tolerability, and pharmacokinetics of IgPro20 in subjects with diffuse cutaneous systemic sclerosis (dcSSc). The pharmacokinetic study aims to evaluate the relative bioavailability of IgPro20, and characterize pharmacokinetics of IgPro20 and IgPro10, respectively, in subjects with dcSSc. Safety, tolerability, and pharmacokinetics of IgPro10 will also be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Cutaneous Systemic Sclerosis
Keywords
scleroderma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IgPro20
Arm Type
Experimental
Arm Description
20% liquid formulation of human immunoglobulin for subcutaneous use
Arm Title
IgPro10
Arm Type
Experimental
Arm Description
10% liquid formulation of human immunoglobulin for intravenous use
Intervention Type
Biological
Intervention Name(s)
IgPro20
Other Intervention Name(s)
Hizentra
Intervention Description
Human normal immunoglobulin for subcutaneous administration
Intervention Type
Biological
Intervention Name(s)
IgPro10
Other Intervention Name(s)
Privigen
Intervention Description
Human normal immunoglobulin for intravenous administration
Primary Outcome Measure Information:
Title
Number of subjects with adverse events (AEs) for IgPro20
Time Frame
Up to 16 weeks
Title
Percentage of subjects with AEs for IgPro20
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro20
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro20
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro20
Time Frame
Up to 16 weeks
Title
Number of patients with AEs categorized as infusion site reactions (ISRs) for IgPro20
Time Frame
Up to 16 weeks
Title
Percentage of patients with AEs categorized as ISRs for IgPro20
Time Frame
Up to 16 weeks
Title
Rate of ISRs per subject for IgPro20
Time Frame
Up to 16 weeks
Title
Rate of ISRs per infusion for IgPro20
Time Frame
Up to 16 weeks
Title
Onset of ISRs for IgPro20
Time Frame
Up to 16 weeks
Title
Duration of ISRs for IgPro20
Time Frame
Up to 16 weeks
Secondary Outcome Measure Information:
Title
IgPro20 relative bioavailability (%F)
Time Frame
Up to 16 weeks
Title
Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro20
Time Frame
Up to 240 hours after first infusion
Title
Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro20
Time Frame
Up to 240 hours after first infusion
Title
Maximum plasma drug concentration (Cmax) for IgPro20
Time Frame
Up to 240 hours after first infusion
Title
Minimum plasma drug concentration (Ctrough) for IgPro20
Time Frame
Prior to infusion
Title
Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro10
Time Frame
Up to 672 hours after first infusion
Title
Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro10
Time Frame
Up to 672 hours after first infusion
Title
Maximum plasma drug concentration (Cmax) for IgPro10
Time Frame
Up to 672 hours after first infusion
Title
Minimum plasma drug concentration (Ctrough) for IgPro10
Time Frame
Prior to infusion
Title
Number and percentage of subjects with AEs for IgPro10
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro10
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro10
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro10
Time Frame
Up to 16 weeks
Title
Number and percentage of subjects with AEs categorized as ISRs for IgPro10
Time Frame
Up to 16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years (male or female) at time of providing written informed consent
Documented diagnosis of systemic sclerosis (scleroderma) according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria 2013 (diffuse cutaneous form of SSc).
Modified Rodnan Skin Score (mRSS) ≥ 15 and ≤ 45 at screening
Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
Capable of providing written informed consent and willing and able to adhere to all protocol requirements
Exclusion Criteria:
Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, as determined by the investigator. Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy at screening are not excluded
Subject has mRSS > 2 at the potential subcutaneous (SC) infusion sites
History of skin condition precluding SC infusion, or clinical signs and symptoms of a chronic skin disease other than systemic sclerosis or skin manifestation of an allergic disease or other dermatological conditions that would interfere with trial assessments or compromise safety (eg, dermatitis, eczema, psoriasis)
Subject has clinical signs and symptoms of skin irritation (eg, pruritus, burning, erythema) or hypo/ hyperpigmentation (eg, scars, tattoos) at the potential SC infusion sites
Significant pulmonary arterial hypertension as documented by mean pulmonary arterial pressure > 30 mmHg on right heart catheterization requiring SC or IV prostacyclin or use of dual oral therapies
Forced vital capacity < 50% predicted or a diffusing capacity of the lung for carbon dioxide (DLCO) ≤ 40% predicted (corrected for hemoglobin)
A female who is pregnant, breastfeeding, or is a woman of childbearing potential who does not agree to use acceptable methods of contraception; a male who does agree to use acceptable methods of contraception.
Evidence of chronic kidney disease with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 or if subject is receiving dialysis. Subjects with current confirmed diagnosis of diabetes mellitus requiring medication with an eGFR < 90 ml/min/1.73m2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Uniklinik Köln, innere Medizin
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
ASST Spedali Civili di Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Azienda Ospedaliera Gaetano Pini
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Uniwersytecki Szpital Kliniczny W Bialymstoku
City
Bialystok
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Szpital Kliniczny Jezus
City
Warsaw
ZIP/Postal Code
02-008
Country
Poland
Facility Name
Narodowy Instytut Geriatrii
City
Warsaw
ZIP/Postal Code
02-637
Country
Poland
Facility Name
The Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
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 IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)
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