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

• ClinicalTrials.gov Identifier: NCT04138485
• Recruitment Status: Recruiting
• First Posted: October 24, 2019
• Last Update Posted: March 23, 2020
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: October 14, 2019
• First Posted Date: October 24, 2019
• Last Update Posted Date: March 23, 2020
• Actual Study Start Date: December 20, 2019
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 22, 2019): Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo [ Time Frame: Over 48 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 22, 2019)

• Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events [ Time Frame: Over 48 weeks ]
• Proportion of responders (ACR CRISS > 0.6) [ Time Frame: Over 48 weeks ]
• Mean change from Baseline in Modified Rodnan Skin Score (mRSS) [ Time Frame: Baseline and over48 weeks ]
• Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: Baseline and over 48 weeks ]
• Mean change from Baseline in Forced Vital Capacity (FVC)% predicted [ Time Frame: Baseline and over 48 weeks ]
• Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted [ Time Frame: Baseline and over 48 weeks ]
• Mean change from Baseline in Physician Global Assessment (MDGA) [ Time Frame: Baseline and over 48 weeks ]
  MDGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor)
• Mean change from Baseline in Patient Global Assessment (PGA) [ Time Frame: Baseline and over 48 weeks ]
  PGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor)
• Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale [ Time Frame: Baseline and over 48 weeks ]
  This survey consists of 34 questions and items are scored on a scale of 0 (better health) to 3 (worse health). Scores are combined to form total score.
• Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo [ Time Frame: Baseline and up to 48 weeks ]
• Proportion of responders in mRSS [ Time Frame: Up to 48 weeks ]
  Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo
• Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo [ Time Frame: Over 48 weeks ]
  Treatment failure - defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all-cause mortality
• Proportion of subjects with events at Week 48 in IgPro10 vs Placebo [ Time Frame: Over 48 weeks ]
  Events defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all -cause mortality
• Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo [ Time Frame: Baseline and over 48 weeks ]
• Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo [ Time Frame: Baseline and over 48 weeks ]
• Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo [ Time Frame: Baseline and over 48 weeks ]
• Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) [ Time Frame: Over 48 weeks ]
• Percentage of subjects with AEs, TEAEs, SAEs, AESIs [ Time Frame: Over 48 weeks ]
• Concentration of serum trough IgG levels at Baseline and prior to first infusion [ Time Frame: Baseline and up to 72 weeks ]
• Mean change from Baseline in Modified Rodnan skin score (mRSS) [ Time Frame: Baseline and over 72 weeks ]
• Mean change from Baseline in Patient global assessment (PGA) [ Time Frame: Baseline and over 72 weeks ]
• Proportion of responders (ACR CRISS > 0.6) [ Time Frame: Over 72 weeks ]
• Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: Baseline and over 72 weeks ]
• Mean change from Baseline in Forced Vital Capacity (FVC)% predicted [ Time Frame: Baseline and over 72 weeks ]
• Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted [ Time Frame: Baseline and over 72 weeks ]
• Mean change from Baseline in Physician Global Assessment (MDGA) [ Time Frame: Baseline and over 72 weeks ]
• Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) [ Time Frame: Over 72 weeks ]
• Percentage of subjects with AEs, TEAEs, SAEs, AESIs [ Time Frame: Over 72 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of IgPro10 in Adults With Systemic Sclerosis (SSc)
• Official Title: A Randomized, Multicenter, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of IgPro10 (Intravenous Immunoglobulin, Privigen®) for the Treatment of Adults With Systemic Sclerosis

Brief Summary

This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period.

Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diffuse Cutaneous Systemic Sclerosis

Intervention

• Biological: IgPro10
  10% liquid formulation of human immunoglobulin for IVIG
  Other Name: Human normal immunoglobulin
• Biological: Placebo
  0.5% human albumin solution stabilized with 250 mmol/L L-proline
  Other Name: Albumin

Study Arms

• Experimental: IgPro10
  10% liquid formulation of human immunoglobulin for intravenous use
  Intervention: Biological: IgPro10
• Placebo Comparator: Placebo
  0.5% human albumin solution stabilized with 250 mmol/L L-proline
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 22, 2019): 144
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2023
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 1. Age ≥18 years (male or female) at time of providing written informed consent
• Documented diagnosis of dcSSc according to ACR / EULAR criteria 2013
• mRSS ≥ 15 and ≤ 45
• Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
• Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation.

Exclusion Criteria:

• Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, and dermatomyositis, as determined by the investigator Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy or myositis at Screening are not excluded
• Positive anti-centromere autoantibodies at Screening
• Evidence of severe chronic kidney disease with estimated glomerular filtration rate < 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or receiving dialysis. Additionally, subjects with current confirmed diagnosis of diabetes mellitus and requiring medication, with eGFR < 90 mL/min/1.73m2 will be excluded from the study.
• History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary
• Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation
• Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden)
• Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess)
• Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year
• Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L)
• Known IgA deficiency or serum IgA level < 5% lower limit of normal

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Registration Coordinator; 610-878-4000; clinicaltrials@cslbehring.com

• Listed Location Countries: Argentina, Australia, Belgium, Canada, France, Germany, Italy, United States

Administrative Information

• NCT Number: NCT04138485
• Other Study ID Numbers: IgPro10_2001; 2019-000906-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systemic 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: CSL Behring
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; CSL Behring

• PRS Account: CSL Behring
• Verification Date: December 2019