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

CSL Behring

Status and phase: Completed; Phase 2

Conditions: Diffuse Cutaneous Systemic Sclerosis

Treatments: Biological: IgPro10; Biological: IgPro20

Study type: Interventional

Funder types: Industry

Identifiers

NCT04137224

IgPro20_2001

2018-003149-41 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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27 participants in 2 patient groups

Sequence A (IgPro20/IgPro10)

Experimental group

Description:

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.

Treatment:

Biological: IgPro20

Biological: IgPro10

Sequence B (IgPro10/IgPro20)

Experimental group

Description:

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:

Biological: IgPro20

Biological: IgPro10