AzTrials
AzTrials

Membranous NephropathyPhase 2ORIONNCT05050214

Obinutuzumab in Primary MN

A Phase 2 study testing Obinutuzumab in people with Membranous Nephropathy, run by Mario Negri Institute for Pharmacological Research at 2 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Primary membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease, that represents one of the most frequent causes of nephrotic syndrome in adults. The first-generation chimeric anti-CD20 monoclonal antibody rituximab is effective in inducing MN remission in the majority of patients, but a… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Membranous Nephropathy
What is being tested?
Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesItaly
Study dates
18 Feb 2022to 20 Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults (≥18 years old) on the day of signing informed consent.
  • Biopsy-proven primary membranous nephropathy.
  • Availability of a recent (over the last six months) diagnostic kidney biopsy to confirm the diagnosis of membranous nephropathy and quantify the severity of chronic changes and the number of glomerular podocytes.
  • High-risk of progression to end-stage kidney disease due to persistent nephrotic-range proteinuria (urinary protein excretion > 3.5 g/24-hours as a median of three consecutive measurements) despite background treatment with RAS-inhibitors (ACEi and/or ARBs) at the maximum tolerated doses for at least six months before inclusion.
  • Failure to definitively and effectively respond to rituximab therapy because of the following:
  • RITUXIMAB-INTOLERANCE, i.e. any previous severe hypersensitivity reaction to rituximab (acute grade III or IV adverse reactions requiring advanced care, or late reactions including delayed serum sickness syndrome) that, independent of response to treatment, preclude further exposure to the drug; or
Show all 11Show fewer
  • RITUXIMAB-RESISTANCE: no evidence of nephrotic syndrome complete remission (24-hour proteinuria < 0.3 g/day, normal serum albumin and stable renal function) or partial remission (24-hour proteinuria < 3.5 g/day with > 50% decrease from baseline, normal serum albumin and stable renal function) along with detectable circulating CD19+ lymphocytes for at least 6 months after rituximab administration or
  • RITUXIMAB-DEPENDENCE: frequently-relapsing nephrotic syndrome (≥ 2 relapses) with nephrotic-range proteinuria for ≥ 50% of time in the 24 months preceding enrolment initial remission after rituximab administration
  • Estimated GFR/eGFR) ≥30 mL/min/1.73 m2 (calculated using the CKD-EPI equation) or qualified endogenous creatinine clearance ≥30 mL/min/1.73 m2 based on 24-hour urine collection during screening.
  • Ability to understand and provide a valid written consent to the study according to the guidelines of the Declaration of Helsinki.
  • Compliance with an effective contraception without interruption, from 28 days before treatment start up to 18 months after treatment discontinuation, agreeing not to donate semen during treatment and for 18 months after discontinuation (if the patient is male), or to undergo pregnancy test during the course of the study (if the patient is female). (According to 2014 CTFG "Recommendations related to contraception and pregnancy testing in clinical trials").

Who cannot join

  • Secondary forms of membranous nephropathy (associated with systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine, and others).
  • Rituximab treatment or any other prolonged (i.e. for more than two weeks) immunosuppressive treatment in the 6 months preceding anti-CD20 infusion.
  • Uncontrolled hypertension (systolic BP ≥160 and/or diastolic BP >90 mmHg despite therapy).
  • Active bacterial, viral and/or fungal infections.
  • Seropositivity for HIV, regardless of viral load.
  • Active or recent (< 5 years before enrolment) history of malignancy.
Show all 13Show fewer
  • Known hypersensitivity or allergy to any of the medicaments under investigation.
  • Any other serious medical condition, uncontrolled intercurrent illness or laboratory abnormality that, according to the investigator's judgement, would constitute an unacceptable risk of premature discontinuation from the study.
  • Patients with previous hepatitis B virus infection (seropositive for anti-HBcAb), planning a vaccination with live virus vaccines
  • Known history of drug induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
  • Pregnancy or breast-feeding
  • Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method (According to 2014 CTFG "Recommendations related to contraception and pregnancy testing in clinical trials").
  • Legal incapacity, limited legal capacity, intellectual disability, uncooperative attitude or any other evidence that the patient will not be able to understand the study aims and procedures.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • ASST HPG23 - Unità di Nefrologia

    Bergamo, BG, 24100

  • Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

    Ranica, BG, 24020

Other trials in Italy

About this study

Official title: Obinutuzumab for Primary Membranous Nephropathy: a Pilot Study in Patients With Rituximab-resistant or Rituximab-dependent Nephrotic Syndrome and in Patients Intolerant to Rituximab (the ORION Study)

Primary membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease, that represents one of the most frequent causes of nephrotic syndrome in adults. The first-generation chimeric anti-CD20 monoclonal antibody rituximab is effective in inducing MN remission in the majority of patients, but a significant fraction of them can experience disease relapses that require multiple re-treatments over time. Repeated infusions may result in hypersensitivity reactions, which contraindicate further treatment with rituximab. Independent of previous treatment response, Rituximab-Intolerant patients require a safe and effective therapeutic alternative that could reduce the risk of hypersensitivity reactions. On the other end a substantial proportion of patients do not benefit of rituximab therapy and might benefit of other anti CD20 monoclonal antibodies. A few patients transiently benefit of rituximab but their relapses after rituximab administration are so frequent that they spend most of their live with nephrotic range proteinuria (rituximab-dependent patients). Obinutuzumab is a humanized monoclonal antibody with enhanced B cell-depleting potential. Due to humanization and glycoengineering, this drug may be safe and effective in inducing disease remission even in patients with prior hypersensitivity reactions to rituximab. Moreover, it has been found to be effective in patients with membranous nephropathy who failed to respond to rituximab.

Being tested
Obinutuzumab
Keywords
obinutuzumab, rituximab, membranous nephropathy, B cells, anti-PLA2R
Medical subject headings
Glomerulonephritis, Membranous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabDrug

    Also called GAZYVA, GAZYVARO

    Each patient will be treated for 1 month and received a total of 3 doses. The first dose of Obinutuzumab (1000 mg) will be split in two separate infusions; on the first day each patient will receive 100 mg and the next day 900 mg of Obinutuzumab. Obinutuzumab (1000 mg) will be also administered at two and four weeks after the first infusion. Obinutuzumab will be administered after standard premedication.

Study groups in NCT05050214
Study groupRoleWhat they receive
Experimental: GAZYVA, GAZYVARO(Obinutuzumab)ExperimentalParticipants will receive Obinutuzumab 1000 mg solution for infusion (total dose of 3000 mg in 30 days).
Receives: Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete remission or partial remission of nephrotic syndrome.

    Measured: Changes from baseline and 12 months from Obinutuzumab treatment .

  2. Serious and non-serious adverse events

    Measured: Through study completion, an average of 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2021
  2. Study start18 Feb 2022
  3. Primary completion20 Feb 2026
  4. Study completion20 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05050214
Sponsor's protocol ID
ORION
Other IDs
2021-004864-81
Acronym
ORION
Status last verified
Oct 2026
First submitted
9 Sep 2021
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Obinutuzumab in people with Membranous Nephropathy, run by Mario Negri Institute for Pharmacological Research at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete remission or partial remission of nephrotic syndrome. (time frame: Changes from baseline and 12 months from Obinutuzumab treatment .). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05050214.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in