Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)

• ClinicalTrials.gov Identifier: NCT04137224
• Recruitment Status: Completed
• First Posted: October 23, 2019
• Last Update Posted: August 3, 2022
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

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.

Condition or disease	Intervention/treatment	Phase
Diffuse Cutaneous Systemic Sclerosis	Biological: IgPro20; Biological: IgPro10	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 19, 2019
• Actual Primary Completion Date: May 17, 2022
• Actual Study Completion Date: May 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: IgPro20; 20% liquid formulation of human immunoglobulin for subcutaneous use	Biological: IgPro20; Human normal immunoglobulin for subcutaneous administration; Other Name: Hizentra
Experimental: IgPro10; 10% liquid formulation of human immunoglobulin for intravenous use	Biological: IgPro10; Human normal immunoglobulin for intravenous administration; Other Name: Privigen

Outcome Measures

Primary Outcome Measures :

1. Number of subjects with adverse events (AEs) for IgPro20 [ Time Frame: Up to 16 weeks ]
2. Percentage of subjects with AEs for IgPro20 [ Time Frame: Up to 16 weeks ]
3. Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro20 [ Time Frame: Up to 16 weeks ]
4. Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro20 [ Time Frame: Up to 16 weeks ]
5. Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro20 [ Time Frame: Up to 16 weeks ]
6. Number of patients with AEs categorized as infusion site reactions (ISRs) for IgPro20 [ Time Frame: Up to 16 weeks ]
7. Percentage of patients with AEs categorized as ISRs for IgPro20 [ Time Frame: Up to 16 weeks ]
8. Rate of ISRs per subject for IgPro20 [ Time Frame: Up to 16 weeks ]
9. Rate of ISRs per infusion for IgPro20 [ Time Frame: Up to 16 weeks ]
10. Onset of ISRs for IgPro20 [ Time Frame: Up to 16 weeks ]
11. Duration of ISRs for IgPro20 [ Time Frame: Up to 16 weeks ]

Secondary Outcome Measures :

1. IgPro20 relative bioavailability (%F) [ Time Frame: Up to 16 weeks ]
2. 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 ]
3. Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro20 [ Time Frame: Up to 240 hours after first infusion ]
4. Maximum plasma drug concentration (Cmax) for IgPro20 [ Time Frame: Up to 240 hours after first infusion ]
5. Minimum plasma drug concentration (Ctrough) for IgPro20 [ Time Frame: Prior to infusion ]
6. 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 ]
7. Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro10 [ Time Frame: Up to 672 hours after first infusion ]
8. Maximum plasma drug concentration (Cmax) for IgPro10 [ Time Frame: Up to 672 hours after first infusion ]
9. Minimum plasma drug concentration (Ctrough) for IgPro10 [ Time Frame: Prior to infusion ]
10. Number and percentage of subjects with AEs for IgPro10 [ Time Frame: Up to 16 weeks ]
11. Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro10 [ Time Frame: Up to 16 weeks ]
12. Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro10 [ Time Frame: Up to 16 weeks ]
13. Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro10 [ Time Frame: Up to 16 weeks ]
14. Number and percentage of subjects with AEs categorized as ISRs for IgPro10 [ Time Frame: Up to 16 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Germany

Charité Universitätsmedizin Berlin

Berlin, Germany, 10117

Uniklinik Köln, innere Medizin

Köln, Germany, 50937

Italy

ASST Spedali Civili di Brescia

Brescia, Italy, 25123

Azienda Ospedaliera Gaetano Pini

Milano, Italy, 20122

Poland

Uniwersytecki Szpital Kliniczny W Bialymstoku

Bialystok, Poland, 15-276

Szpital Kliniczny Jezus

Warsaw, Poland, 02-008

Narodowy Instytut Geriatrii

Warsaw, Poland, 02-637

United Kingdom

The Royal Free Hospital

London, United Kingdom, NW3 2QG

Sponsors and Collaborators

CSL Behring

Investigators

• Study Director: Study Director; CSL Behring

More Information

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT04137224
• Other Study ID Numbers: IgPro20_2001; 2018-003149-41 ( EudraCT Number )
• First Posted: October 23, 2019
• Last Update Posted: August 3, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• 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; 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CSL Behring:

scleroderma

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Immunoglobulins, Intravenous; Immunologic Factors; Physiological Effects of Drugs