Clinical trial NCT04137224: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Cutaneous Systemic Sclerosis
Keywords: scleroderma
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-10-23
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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: 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

Primary outcomes:
measure: Number of Participants With at Least One Adverse Event (AE) for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One AE for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One TEAE for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One SAE for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20
timeFrame: From first dose of study drug through last follow-up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One AESI for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With AEs Categorized as ISRs for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Rate of ISRs Per Infusion for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Time to Onset of ISRs for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Duration of ISRs for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
Secondary outcomes:
measure: Relative Bioavailability (%F) of IgPro20
timeFrame: 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)
measure: Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20
timeFrame: 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)
measure: Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20
timeFrame: 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)
measure: Maximum Plasma Drug Concentration (Cmax) for IgPro20
timeFrame: 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)
measure: Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A
timeFrame: Pre-injection at Weeks 5, 9, 13, and 14
measure: Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B
timeFrame: Pre-injection at Weeks 21, 25, 29, and 30
measure: Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10
timeFrame: 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
measure: Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10
timeFrame: 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
measure: Maximum Plasma Drug Concentration (Cmax) for IgPro10
timeFrame: 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
measure: Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A
timeFrame: Pre-infusion at Weeks 21, 25 and 29
measure: Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B
timeFrame: Pre-infusion at Weeks 5, 9 and 13
measure: Number of Participants With at Least One AE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One AE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With at Least One TEAE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One TEAE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With at Least One SAE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One SAE for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With at Least One AESI for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With at Least One AESI for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With AEs Categorized as ISRs for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Percentage of Participants With AEs Categorized as ISRs for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
Other outcomes:
measure: Rate of ISRs Per Participant for IgPro20
timeFrame: From first dose of study drug through last follow up visit (up to 36 weeks)
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Köln
country: Germany
facility: Uniklinik Köln, innere Medizin
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Milano
country: Italy
facility: Azienda Ospedaliera Gaetano Pini
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny W Bialymstoku
city: Warsaw
country: Poland
facility: Szpital Kliniczny Jezus
city: Warsaw
country: Poland
facility: Narodowy Instytut Geriatrii
city: London
country: United Kingdom
facility: The Royal Free Hospital
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: