Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and tolerability of two dose regimens of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with placebo.

Detailed Description
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Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related systemic v anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a potentially life-threatening disease. GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (e.g., capillaries, venules, arterioles, arteries, and veins). MPA is a necrotizing vasculitis that primarily affects capillaries, venules, or arterioles, most commonly manifesting as necrotizing glomerulonephritis and/or pulmonary capillaritis. MPA. Primed neutrophils are activated by ANCA and generate C5a that engages C5a receptors on neutrophils. Therefore, patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease and not in remission. IFX-1 is a monoclonal antibody specifically binding to the soluble human complement split product C5a and the resulting nearly complete blockade of C5a-induced biological effects may be effective in the treatment of subjects with AAV.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Efficacy and Safety Study of IFX-1 in Add-On to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)

Conditions
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Granulomatosis With Polyangiitis (GPA), Microscopic Polyangiitis (MPA)

Intervention / Treatment
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* Drug: IFX-1 low dose
* Drug: IFX-1 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥18 years of age. Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference. Have at least one major item, or at least three other items, or at least two renal items on the Birmingham Vasculitis Activity Score (BVAS) Version 3.0. New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs. Exclusion Criteria: Any other multisystem autoimmune disease Requires mechanical ventilation because of alveolar hemorrhage at Screening. Human immunodeficiency virus, hepatitis B, or hepatitis C viral screening test showing evidence of active or chronic viral infection at Screening or a documented history of the human immunodeficiency virus, hepatitis B, or hepatitis C. Received CYC or RTX 12 weeks before Screening; if on azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or mycophenolate sodium (MPS) at the time of Screening, these drugs must be withdrawn prior to receiving CYC or RTX. Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before Screening. On an oral dose of a GC of more than 10 mg prednisone equivalent at Screening or for more than 6 weeks before Screening. Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin or plasma exchange, antithymocyte globulin, or required dialysis within 12 weeks before Screening. Received a live vaccination within 4 weeks before Screening or planned between Screening and Week 24. Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception (pearl index <1%) such as complete sexual abstinence, combined oral contraceptive, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant, or depot contraceptive injection in combination with a second method of contraception such as condom, cervical cap, or diaphragm with spermicide during the study and for at least 4 weeks after last administration of IFX-1 (timeframes for SOC have to be considered as described in the respective Prescribing Information).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFX-1 low dose<br>Will receive IFX-1 low dose regimen diluted in sodium chloride solution | Drug: IFX-1 low dose<br>* Single IV infusions of IFX-1<br>* Other names: CaCP29;|
| Experimental: IFX-1 high dose<br>Will receive IFX-1 high dose regimen diluted in sodium chloride solution | Drug: IFX-1 high dose<br>* Single IV infusions of IFX-1<br>* Other names: CaCP29;|
| Placebo Comparator: Placebo<br>Will receive placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Participants With at Least One TEAE Per Treatment Group. | Number and percentage of participants who experience at least one treatment-emergent adverse event (TEAE) per treatment group. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Response | Efficacy Endpoint based on clinical response evaluated through BVAS. Clinical response is defined as a reduction in BVAS of ≥50% and no worsening in any body system and no administration of rescue medication prior to the response assessment. | Week 16 | 
| Percentage of Participants With Clinical Remission (BVAS = 0) | Efficacy Endpoint that evaluates participants with complete remission | Week 16 | 
| IFX-1 Concentration Pre-dose | Assess the pharmacokinetic of the investigational medicinal product. | Week 16 | 
| IFX 1 Concentration at Predose (0 Hours), After the End of the Infusion (+10minutes), and at 2, 6, 24, and 48 Hours After the Start of the Infusion for Participants in the PK Substudy | Analyze the IMP plasma concentration using a PK model: IFX 1 concentration at predose (0 hours), after the end of the infusion (+10minutes), and at 2, 6, 24, and 48 hours after the start of the infusion for participants in the PK substudy | Weeks 1, 4 and 16 | 
| C5a Plasma Concentration | Pharmacodynamic parameter concentration | Week 16 | 
| IFX-1 Blocking Activity 2.5 nM | Pharmacodynamic Parameter of IFX-1 blocking activity 2.5 nM | Week 16 | 
| IFX-1 Blocking Activity 10 nM | Pharmacodynamic Parameter of IFX-1 blocking activity 10 nM | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), IFX-1, ANCA, AAV