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NCT Number: NCT04629248

A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy

This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CINME, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening
  • Screening urinary protein-to-creatinine ratio (UPCR) >= 5 g/g from 24-hour urine collection after best supportive care for >= 3 months prior to screening or screening UPCR >= 4 g/g after best supportive care for >= 6 months prior to screening
  • eGFR >= 40 mL/min/1.73m^2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m^2 based on 24-hour urine collection during screening
  • Other inclusion criteria may apply

Exclusion criteria

  • Participants with a secondary cause of MN
  • Pregnancy or breastfeeding
  • Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to randomization
  • Severe renal impairment, including the need for dialysis or renal replacement therapy
  • Type 1 or 2 diabetes mellitus
  • Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to or during screening; or cyclophosphamide, tacrolimus, or cyclosporin less than 6 months prior to or during screening
  • Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation
  • Known active infection of any kind or recent major episode of infection
  • Major surgery requiring hospitalization within the 4 weeks prior to screening
  • Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening
  • Intolerance or contraindication to study therapies
  • Other exclusion criteria may apply

Treatment and study plan

Obinutuzumab

Drug

Open Label: An intravenous (IV) infusion of 1000 milligram (mg) of obinutuzumab will be administered at Week 0, Week 2, Week 24, and Week 26. Participants who relapse during the open-label treatment period may be eligible for further treatment.

Other names: Gazyva

Tacrolimus

Drug

Open Label: Participants will receive tacrolimus at a starting oral dose (PO) of 0.05 mg/kilogram (kg) (participant dry weight) per day divided into two equal doses given at 12-hour intervals, titrated to serum trough level 5-7 Nanograms per millilitre (ng/mL). Optimized tacrolimus dose will be maintained for a maximum 52 weeks dependent on response and then tapered over 8 weeks. Participants who relapse during the open-label treatment period will have their dose of tacrolimus tapered over 8 weeks and may be eligible for further treatment.

methylprednisolone

Drug

Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.

Acetaminophen

Drug

Premedication: Acetaminophen (650-1000 mg, or equivalent dose of a similar agent) PO or IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.

diphenhydramine

Drug

Premedication: Diphenhydramine (50 mg, or equivalent dose of a similar agent) PO or IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.

Primary outcomes

  1. Percentage of Participants who Achieve a Complete Remission (CR) at Week 104

    Time frame: Week 104

Secondary outcomes

  1. Percentage of Participants who Achieve an Overall Remission at Week 104

    Time frame: Week 104

  2. Percentage of Participants who Achieve CR at Week 76

    Time frame: Week 76

  3. Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission

    Time frame: Up to 8 years

  4. Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline

    Time frame: Up to 8 years

  5. Mean Change in T-score from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104

    Time frame: Baseline to Week 104

    Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.

  6. Duration of CR

    Time frame: Up to 8 years

  7. Change in anti-PLA2R Autoantibody Titer

    Time frame: Baseline to Week 52

  8. Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104

    Time frame: Baseline to Week 104

    Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale

  9. Percentage of Participants with Adverse Events (AEs)

    Time frame: Up to 8 years

    Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  10. Percentage of Participants with AEs of Special Interest (AESIs)

    Time frame: Up to 8 years

    AESIs are required to be reported by the investigator to the Sponsor immediately

  11. Peripheral B-cell Counts at Specified Timepoints

    Time frame: Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 156, 182, 208 and every 26 weeks thereafter

  12. Serum Concentrations of Obinutuzumab at Specified Timepoints

    Time frame: Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 143, 156, 169, 182, 195, 208, every 26 weeks thereafter

  13. Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline

    Time frame: Open Label: Baseline; Escape Treatment: Week 0

  14. Incidence of ADAs during the study

    Time frame: Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase III Randomized, Open-Label Active Comparator-Controlled Multicenter Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients With Primary Membranous Nephropathy

Acronym: MAJESTY

Important dates

Study start
2021
Primary completion
2025
Study completion
2027
First posted
Nov 16, 2020
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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