What side effects are associated with this type of intervention?

Common treatments for vasculitis, such as monoclonal antibodies targeting CD20 (e.g., rituximab and obinutuzumab), and immunosuppressive therapies like cyclophosphamide, have several known side effects. Rituximab can cause infusion reactions, infections, and in rare cases, severe allergic reactions. Cyclophosphamide is associated with risks of infections, bladder toxicity, and potential long-term risks like infertility and secondary malignancies. Both treatments require careful monitoring for adverse events to manage these risks effectively.

What prior FDA approvals exist?

Rituximab, a monoclonal antibody targeting CD20, has been FDA-approved for the treatment of certain types of vasculitis, such as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Rituximab works by depleting B cells, which are implicated in the pathogenesis of these diseases. Obinutuzumab, another CD20 monoclonal antibody, is being studied for its efficacy in treating vasculitis, similar to rituximab. These therapies aim to reduce disease activity by targeting and depleting B cells, thereby modulating the immune response.

What other types of research exist?

Promising novel alternatives to Obinutuzumab for Vasculitis patients in 2024 include Rituximab, which is another anti-CD20 monoclonal antibody, and mycophenolate mofetil (MMF) as an immunosuppressive agent. Additionally, newer therapies such as CD19-targeted CAR T cells and other emerging biologics targeting B cells or specific inflammatory pathways may also be considered.

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Monoclonal Antibodies

Obinutuzumab for Granulomatosis with Polyangiitis

Phase 2

Waitlist Available

Led By Ulrich Specks, MD

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Positivity for ANCA, directed against proteinase-3 (PR3)

Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis or microscopic polyangiitis)

Must not have

History of intolerance to rituximab or other chimeric monoclonal antibodies (e.g., infliximab)

Daily use of non-steroidal anti-inflammatory drugs (NSAIDs)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 18 months

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing obinutuzumab, a medication that helps the immune system target and destroy specific cells, on patients with PR3-AAV, a type of blood vessel inflammation. The treatment works by helping the body’s immune system find and eliminate harmful cells causing the inflammation.

Who is the study for?

This trial is for adults with ANCA-associated vasculitis, specifically PR3-AAV. Participants must have a certain level of disease severity and be vaccinated against COVID-19. Women who can bear children and men with partners who can must use contraception. Exclusions include severe allergies to monoclonal antibodies, recent live vaccines, active infections (including hepatitis B/C or HIV), uncontrolled diseases that could affect the trial's outcome, history of certain malignancies within 5 years, and intolerance to rituximab.

What is being tested?

The PRRR study tests obinutuzumab's effectiveness and safety in treating PR3-AAV compared to rituximab. It aims to see if obinutuzumab can induce longer remission periods in patients with this type of vasculitis by targeting immune cells involved in the disease process.

What are the potential side effects?

Potential side effects may include allergic reactions related to infusion, increased risk of infections due to immune system suppression, possible blood disorders like low white cell counts which increase infection risks further, liver enzyme elevations indicating potential liver issues, and general symptoms such as fatigue or nausea.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My blood test is positive for ANCA against PR3.

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I have been diagnosed with a specific type of vasculitis (GPA or MPA).

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I agree to use birth control for 18 months (if female) or 180 days (if male) after my last treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a bad reaction to rituximab or similar medications.

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I use NSAIDs like ibuprofen daily.

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I have undergone plasma exchange in the last 3 months.

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I currently have an active COVID-19 infection.

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I do not have an active infection.

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I do not have active hepatitis B or C, and no history of HIV, hepatitis B, or C.

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I have had a serious infection like bone infection or lung abscess in the last 6 months.

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I have a history of getting infections often.

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I am premenopausal and either pregnant, breastfeeding, or not using birth control.

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My blood tests show low white cells, hemoglobin, or platelets.

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I have been diagnosed with eosinophilic granulomatosis with polyangiitis.

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I have a history of anti-GBM disease.

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I have not received a live vaccine in the last 4 weeks.

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I need more than 10 mg of prednisone daily for a condition like asthma or IBD.

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My liver disease is severe and may affect my trial participation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Patients to Achieve Both Complete Remission and Seronegativity for ANCA.

Secondary study objectives

Number of Patients to Achieve Sustained Complete Remission 12 Months

Number of Patients to Achieve Sustained Complete Remission 18 Months

Number of Patients to Achieve Sustained Complete Remission 6 Months

Side effects data

From 2019 Phase 3 trial • 229 Patients • NCT02264574

44%

Neutropenia

35%

Thrombocytopenia

35%

Diarrhea

29%

Cough

24%

Arthralgia

23%

Infusion related reaction

19%

Fatigue

19%

Back pain

19%

Hypertension

17%

Anaemia

17%

Constipation

17%

Pyrexia

16%

Upper respiratory tract infection

15%

Rash maculo-papular

14%

Muscle spasms

14%

Atrial fibrillation

13%

Hyperuricaemia

13%

Nausea

13%

Nasopharyngitis

12%

Insomnia

12%

Urinary tract infection

12%

Oedema peripheral

11%

Conjunctivitis

11%

Asthenia

11%

Pneumonia

11%

Dyspnoea

11%

Vomiting

11%

Pain in extremity

11%

Dizziness

10%

Cataract

10%

Decreased appetite

Spontaneous haematoma

Anxiety

Fall

Rash

Headache

Iron deficiency

Abdominal pain

Dyspepsia

Vision blurred

Pruritus

Bronchitis

Lacrimation increased

Respiratory tract infection

Blood creatine increased

Productive cough

Oropharyngeal pain

Gastrooesophageal reflux disease

Hypokalaemia

Dry eye

Chills

Myalgia

Depression

Dry Skin

Ecchymosis

Onychoclasis

Palpitations

Stomatitis

Peripheral swelling

Epistaxis

Herpes zoster

Increased tendency to bruise

Hyperglycaemia

Musculoskeletal pain

Haematuria

Petechiae

Cellulitis

Contusion

Tremor

Febrile neutropenia

Adenocarcinoma of colon

Acute coronary syndrome

Gastroenteritis

Weight decreased

Septic shock

Femur fracture

Osteoarthritis

Transient ischaemic attack

Cardiac arrest

Angina pectoris

Death

Cerebrovascular accident

Acute kidney injury

Renal failure

Oesophageal rupture

Respiratory failure

Compartment syndrome

Invasive ductal breast carcinoma

Colorectal cancer

Malignant melanoma

Non-small cell lung cancer

Uterine prolapse

Bronchitis chronic

Peripheral ischaemia

Myelodysplastic syndrome

Haemoptysis

Pleural effusion

Bronchopulmonary aspergillosis

Cardiac failure congestive

Gastritis

Concussion

Arthritis

Inclusion body myositis

Colorectal cancer metastatic

Ischaemic stroke

Bacterial sepsis

Leukopenia

Acute myocardial infarction

Pericarditis

Stress cardiomyopathy

Goitre

Haemorrhoids

Impaired gastric emptying

Proctitis

Small intestinal obstruction

Catheter site haematoma

Multi-organ disorder

Cholelithiasis

Abscess

Bursitis infective staphylococcal

Erysipelas

Escherichia sepsis

Escherichia urinary tract infection

Infective aneurysm

Listeria sepsis

Lower respiratory tract infection

Pneumocystis jirovecii pneumonia

Pneumonia bacterial

Pneumonia klebsiella

Prostate infection

Sinusitis fungal

Urosepsis

Jaw fracture

Pubis fracture

Rib fracture

Spinal compression fracture

Thoracic vertebral fracture

Traumatic haematoma

Upper limb fracture

Diabetes mellitus inadequate control

Adenocarcinoma gastric

Basal cell carcinoma

Benign renal neoplasm

Squamous cell carcinoma

Syncope

Acute psychosis

Complete Suicide

Soft tissue infection

Osteoma

Atrial tachycardia

Retinal detachment

Herpes Zoster

Oral herpes

Pharyngitis

Streptococcal bacteraemia

Cardiac failure

Myocardial infarction

Sudden Death

Incisional hernia

Hypercalcaemia

Hypomagnesaemia

Aplastic anaemia

Inguinal hernia

Large intestine polyp

Cerebral ischaemia

Depressed level of consciousness

Confusional state

Nephrolithiasis

Urinary retention

Benign prostatic hyperplasia

Hypotension

100%

80%

60%

40%

20%

Study treatment Arm

IBR+OB

CLB+OB

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Intravenous dose of obinutuzumabExperimental Treatment1 Intervention

Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of obinutuzumab

Group II: Intravenous dose of rituximabActive Control1 Intervention

Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of rituximab

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Obinutuzumab

FDA approved

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for vasculitis, such as obinutuzumab, work by targeting and depleting B cells, which are a type of white blood cell involved in the immune response. Obinutuzumab is a monoclonal antibody that binds to the CD20 protein on the surface of B cells, leading to their destruction. This is crucial for vasculitis patients because B cells can produce antibodies that attack the body's own tissues, causing inflammation and damage to blood vessels. By depleting B cells, these treatments help reduce the autoimmune response, control inflammation, and prevent further tissue damage. Other treatments, like cyclophosphamide and rituximab, also aim to suppress the immune system to achieve similar outcomes, thereby improving patient prognosis and quality of life.