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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04137224




Registration number
NCT04137224
Ethics application status
Date submitted
21/10/2019
Date registered
23/10/2019

Titles & IDs
Public title
Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)
Scientific 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)
Secondary ID [1] 0 0
2018-003149-41
Secondary ID [2] 0 0
IgPro20_2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Cutaneous Systemic Sclerosis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - IgPro20
Treatment: Other - IgPro10

Experimental: Sequence A (IgPro20/IgPro10) - Participants received IgPro20 of a total dose of 0.5 grams per kilogram (g/kg) over 2 sessions per week as a subcutaneous (SC) injection for up to 16 weeks in Treatment Period 1 followed by IgPro10 of a total dose of 2 g/kg over 2 to 5 sessions on consecutive days every 4 weeks as an intravenous (IV) infusion for up to 16 weeks in Treatment Period 2.

Experimental: Sequence B (IgPro10/IgPro20) - Participants received IgPro10 of a total dose of 2 g/kg over 2 to 5 sessions on consecutive days every 4 weeks as an IV infusion for up to 16 weeks in Treatment Period 1 followed by IgPro20 of a total dose of 0.5 g/kg over 2 sessions per week as a SC injection for up to 16 weeks in Treatment Period 2.


Treatment: Other: IgPro20
Human normal immunoglobulin for subcutaneous administration

Treatment: Other: IgPro10
Human normal immunoglobulin for intravenous administration

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With at Least One Adverse Event (AE) for IgPro20
Timepoint [1] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [2] 0 0
Percentage of Participants With at Least One AE for IgPro20
Timepoint [2] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [3] 0 0
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20
Timepoint [3] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [4] 0 0
Percentage of Participants With at Least One TEAE for IgPro20
Timepoint [4] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [5] 0 0
Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20
Timepoint [5] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [6] 0 0
Percentage of Participants With at Least One SAE for IgPro20
Timepoint [6] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [7] 0 0
Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20
Timepoint [7] 0 0
From first dose of study drug through last follow-up visit (up to 36 weeks)
Primary outcome [8] 0 0
Percentage of Participants With at Least One AESI for IgPro20
Timepoint [8] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [9] 0 0
Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20
Timepoint [9] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [10] 0 0
Percentage of Participants With AEs Categorized as ISRs for IgPro20
Timepoint [10] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [11] 0 0
Rate of ISRs Per Infusion for IgPro20
Timepoint [11] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [12] 0 0
Time to Onset of ISRs for IgPro20
Timepoint [12] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [13] 0 0
Duration of ISRs for IgPro20
Timepoint [13] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [14] 0 0
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20
Timepoint [14] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [15] 0 0
Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20
Timepoint [15] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [16] 0 0
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20
Timepoint [16] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Primary outcome [17] 0 0
Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20
Timepoint [17] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [1] 0 0
Relative Bioavailability (%F) of IgPro20
Timepoint [1] 0 0
Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Secondary outcome [2] 0 0
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20
Timepoint [2] 0 0
Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Secondary outcome [3] 0 0
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20
Timepoint [3] 0 0
Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Secondary outcome [4] 0 0
Maximum Plasma Drug Concentration (Cmax) for IgPro20
Timepoint [4] 0 0
Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Secondary outcome [5] 0 0
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A
Timepoint [5] 0 0
Pre-injection at Weeks 5, 9, 13, and 14
Secondary outcome [6] 0 0
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B
Timepoint [6] 0 0
Pre-injection at Weeks 21, 25, 29, and 30
Secondary outcome [7] 0 0
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10
Timepoint [7] 0 0
Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Secondary outcome [8] 0 0
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10
Timepoint [8] 0 0
Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Secondary outcome [9] 0 0
Maximum Plasma Drug Concentration (Cmax) for IgPro10
Timepoint [9] 0 0
Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Secondary outcome [10] 0 0
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A
Timepoint [10] 0 0
Pre-infusion at Weeks 21, 25 and 29
Secondary outcome [11] 0 0
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B
Timepoint [11] 0 0
Pre-infusion at Weeks 5, 9 and 13
Secondary outcome [12] 0 0
Number of Participants With at Least One AE for IgPro10
Timepoint [12] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [13] 0 0
Percentage of Participants With at Least One AE for IgPro10
Timepoint [13] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [14] 0 0
Number of Participants With at Least One TEAE for IgPro10
Timepoint [14] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [15] 0 0
Percentage of Participants With at Least One TEAE for IgPro10
Timepoint [15] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [16] 0 0
Number of Participants With at Least One SAE for IgPro10
Timepoint [16] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [17] 0 0
Percentage of Participants With at Least One SAE for IgPro10
Timepoint [17] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [18] 0 0
Number of Participants With at Least One AESI for IgPro10
Timepoint [18] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [19] 0 0
Percentage of Participants With at Least One AESI for IgPro10
Timepoint [19] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [20] 0 0
Number of Participants With AEs Categorized as ISRs for IgPro10
Timepoint [20] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [21] 0 0
Percentage of Participants With AEs Categorized as ISRs for IgPro10
Timepoint [21] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [22] 0 0
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10
Timepoint [22] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [23] 0 0
Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10
Timepoint [23] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [24] 0 0
Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10
Timepoint [24] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcome [25] 0 0
Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10
Timepoint [25] 0 0
From first dose of study drug through last follow up visit (up to 36 weeks)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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: Participants with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy at screening are not excluded
* Participants has mRSS > 2 at the potential subcutaneous (SC) injection 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)
* Participants has clinical signs and symptoms of skin irritation (eg, pruritus, burning, erythema) or hypo/ hyperpigmentation (eg, scars, tattoos) at the potential SC injection 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 participants are receiving dialysis. Participants with current confirmed diagnosis of diabetes mellitus requiring medication with an eGFR < 90 ml/min/1.73m2

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
Germany
State/province [2] 0 0
Köln
Country [3] 0 0
Italy
State/province [3] 0 0
Brescia
Country [4] 0 0
Italy
State/province [4] 0 0
Milano
Country [5] 0 0
Poland
State/province [5] 0 0
Bialystok
Country [6] 0 0
Poland
State/province [6] 0 0
Warsaw
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 [email protected].

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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.