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

NCT04137224 | Completed Phase 2 Results

• 2 other identifiers: IgPro20_20012018-003149-41
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 9

Brief Summary

This is a prospective, multicenter, randomized, open-label, crossover study to investigate the safety, tolerability, and pharmacokinetics of IgPro20 in participants 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 participants with dcSSc. Safety, tolerability, and pharmacokinetics of IgPro10 will also be evaluated.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Keywords

scleroderma

Outcome Measures

Primary Outcomes (17)

• Number of Participants With at Least One Adverse Event (AE) for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Percentage of Participants With at Least One AE for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Percentage of Participants With at Least One TEAE for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20

  An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Percentage of Participants With at Least One SAE for IgPro20

  An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.

  From first dose of study drug through last follow-up visit (up to 36 weeks)

• Percentage of Participants With at Least One AESI for IgPro20

  AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20

  ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Percentage of Participants With AEs Categorized as ISRs for IgPro20

  ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Rate of ISRs Per Infusion for IgPro20

  ISR rate per infusion = total number of ISRs across all participants while on IgPro20 / total number of IgPro20 Infusions across all participants. ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions NEC', 'Infusion site reactions', or 'Injection site reactions'

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Time to Onset of ISRs for IgPro20

  ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. Time to onset of ISR since the start of the treatment period was reported.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Duration of ISRs for IgPro20

  ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20

  Abnormality criteria:Hematology-Hemoglobin:\<10 g/dL;Platelet count:\<75x10\^9/L or \>500x10\^9/L;White Blood Cell Count:\<3x10\^9/L or \>16x10\^9/L;Neutrophils:absolute \<1.5x10\^9/L,differential \<40%;Lymphocytes:absolute \<0.8x10\^9/L,differential \<10 or \>50%; Biochemistry-Bilirubin:\>1.5xupper limit of normal (ULN);Alkaline phosphatase:\>2.5xULN;Serum Glutamic-oxalacetic transaminase(SGOT), Aspartate transaminase(AST):\>3xULN;Serum glutamic-pyruvic transaminase(SGPT), Alanine transaminase(ALT):\>3xULN;Screening:AST/ALT \>3xULN and Total Bilirubin \>2xULN;Urea nitrogen:\>2.5xULN; Creatinine, serum\>1.5xbaseline assessment or change \>0.3mg/dL since last visit;Glucose,blood (non-fasting):\<55/\>160mg/dL;Calcium:\<7/\>11.5mg/dL;Total protein: \<5/\>9g/dL; Albumin:\<3g/dL;Sodium:\<130/\>150mmol/L;Potassium:\<3/\>5.5mmol/L; Uric acid,serum:\>10mg/dL Males,\>8mg/dL Females;Gamma Glutamyl Transpeptidase:\>2.5xULN; Phosphorus,inorganic:\<2.5/\>5mg/dL;Lactate dehydrogenase:\>3xULN;Urinalysis-Protein:\>20mg/dL.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20

  Clinically significant abnormality criteria for vital signs included Systolic blood pressure (BP): \<100 millimeters of mercury (mmHg) or ≥140 mmHg or ≥140 mmHg and increase \>10 from reference visit; Diastolic BP: \<50 mmHg or ≥90 mmHg or ≥90 mmHg and increase \>10 from reference visit; Pulse rate: \<50 beats/minute or ≥120 beats/minute or ≥120 beats/minute and increase \>15 from reference visit; Weight (kilograms) ≥10% change (increase and decrease) from baseline assessment; Body temperature: \> 39-degree Celsius (°C ) or \<35°C (oral, tympanic, axilla or forehead).

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20

  Clinically significant abnormality criteria for ECG parameters included Heart rate: ≤50 or ≥100 beats/minute; PR Interval: ≥200 millisecond (msec); QRS Interval: ≥120 msec; QT: ≥480 msec; QT interval corrected using Bazett' s formula (QTcB): ≤ 500 msec; QT interval corrected using Fridericia's formula (QTcF): \>500 msec; QT: increase from baseline ≥ 30; QTcB: increase from baseline \< 60 msec; QTcF: increase from baseline ≥ 60.

  From first dose of study drug through last follow up visit (up to 36 weeks)

• Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20

  PFTs include Spirometry which included forced vital capacity (FVC) % Predicted, considered as clinically significant abnormality when decrease is greater than10 percentage points from the reference visit.

  From first dose of study drug through last follow up visit (up to 36 weeks)

Secondary Outcomes (25)

• Relative Bioavailability (%F) of IgPro20

  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)

• Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20

  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)

• Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20

  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)

• Maximum Plasma Drug Concentration (Cmax) for IgPro20

  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)

• Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A

  Pre-injection at Weeks 5, 9, 13, and 14

Other Outcomes (1)

• Rate of ISRs Per Participant for IgPro20

  From first dose of study drug through last follow up visit (up to 36 weeks)

Study Arms (2)

Sequence A (IgPro20/IgPro10)

EXPERIMENTAL

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.

Biological: IgPro20; Biological: IgPro10

Sequence B (IgPro10/IgPro20)

EXPERIMENTAL

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.

Biological: IgPro20; Biological: IgPro10

Interventions

IgPro20 BIOLOGICAL

Human normal immunoglobulin for subcutaneous administration

Also known as: Hizentra

Sequence A (IgPro20/IgPro10); Sequence B (IgPro10/IgPro20)

IgPro10 BIOLOGICAL

Human normal immunoglobulin for intravenous administration

Also known as: Privigen

Sequence A (IgPro20/IgPro10); Sequence B (IgPro10/IgPro20)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (9)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Uniklinik Köln, innere Medizin

Cologne, 50937, Germany

Location

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Gaetano Pini

Milan, 20122, Italy

Location

Uniwersytecki Szpital Kliniczny W Bialymstoku

Bialystok, 15-276, Poland

Location

Szpital Kliniczny Jezus

Warsaw, 02-008, Poland

Location

Narodowy Instytut Geriatrii

Warsaw, 02-637, Poland

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• Denton CP, Kowal-Bielecka O, Proudman SM, Olesinska M, Worm M, Del Papa N, Matucci-Cerinic M, Radewonuk J, Jochems J, Panaite A, Shebl A, Krupa A, Allanore Y, Hofmann JH, Gasior MJ. A phase 2 randomized trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis. Rheumatology (Oxford). 2025 Jun 1;64(6):3657-3666. doi: 10.1093/rheumatology/keaf066.

  PMID: 39909490 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

Hizentra; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: CSL Behring

clinicaltrials@cslbehring.com

610-878-4000

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 23, 2019
• Study Start: September 19, 2019
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

AU (1); PL (3); DE (2); GB (1); IT (2)