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NCT Number: NCT05039619

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants

This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics (PK) of obinutuzumab in adolescent participants (AP) aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN). It will also evaluate open label safety and PK of obinutuzumab in pediatric participants (PP), aged 5 to <12 with LN.

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Key information

Age range

5 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Ser Servicos Especializados Em Reumatologia, Salvador, Estado de Bahia, Brazil

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Participants who are age 12 to <18 years at the time of randomization
  • Participants who are age 5 to <12 years (younger participant cohort) at the time of randomization once recruitment is open. (Investigators will be notified by the Sponsor when recruitment is open to this younger population)
  • International Society of Nephrology and the Renal Pathology Society (ISN/RPS) 2003 Class III or IV active LN demonstrated on renal biopsy performed in the 12 months prior to or during screening
  • Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible
  • Diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria
  • Significant proteinuria defined by a UPCR above > 0.5 based on a first-morning void (FMV) collection at screening
  • During the 12 months prior to or during screening, all participants must have received at least one dose of pulse-range IV methylprednisolone (typically 30 mg/kg, maximum of 1000 mg per dose) or equivalent for the treatment of the current episode of active LN.

Exclusion criteria

  • Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
  • Sclerosis in >50% of glomeruli on renal biopsy
  • Purely chronic Class III(c) or Class IV(c) disease on renal biopsy, defined as the absence of any active lesions
  • Presence of rapidly progressive glomerulonephritis
  • Pure Class V LN
  • Intolerance or contraindication to study therapies
  • Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization
  • History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe Immunodeficiency blood disorders
  • History of serious recurrent or chronic infection
  • History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinoma and squamous cell carcinoma of the skin that have been excised and cured) within the past 5 years
  • Significant or uncontrolled concomitant medical disease which, in the investigator's opinion, would preclude participant participation
  • Currently active alcohol or drug abuse or history of alcohol or drug abuse

Treatment and study plan

Obinutuzumab

Drug

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1, Day 14, Week 24, Week 26 and Week 52.

Other names: Gazyva

Placebo

Drug

Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.

Mycophenolate mofetil

Drug

Mycophenolate Mofetil (MMF) will be taken by home administration orally at a target dose of 1200 mg/m^2/day to a maximum of 2.5g/day from baseline (Day 1) onwards.

Acetaminophen/paracetamol

Drug

Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.

Diphenhydramine hydrochloride (HCl)

Drug

Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.

methylprednisolone

Drug

Methylprednisolone 80 mg IV will be administered as pre-medication prior to infusions.

Prednisone

Drug

Oral prednisone or equivalent corticosteroid will be taken by home administration daily to a maximum dose of 60mg/day followed by a guided taper to 5mg/day or less by Week 24.

Primary outcomes

  1. Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)

    Time frame: Week 76

    CRR is defined as achievement of all of the following:

    • Urinary protein-to-creatinine ratio (UPCR) <0.5 g/g
    • Estimated Glomerular Filtration Rate (eGFR) >=85% of baseline
    • No occurrence of intercurrent events
  2. Percentage of Participants with Adverse Events (PP)

    Time frame: Baseline to Week 76

Secondary outcomes

  1. Percentage of Participants Achieving a CRR (AP)

    Time frame: Weeks 24 and 52

  2. Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP)

    Time frame: Week 76

  3. Percentage of Participants who Achieve a PRR (AP)

    Time frame: Week 76

  4. Percentage of Participants Achieving an Overall Response (CRR or PRR) (AP)

    Time frame: Weeks 24, 52, and 76

    PRR is defined as:

    achievement of all of the following:

    • >=50% reduction in urinary protein-to-creatinine ratio (UPCR) from baseline
    • UPCR < 1 g/g (or < 3 g/g if the baseline UPCR was >=3 g/g)
    • eGFR >=85% of baseline
    • No occurrence of intercurrent events
  5. Change in UPCR (AP)

    Time frame: Baseline to Week 76

  6. Change in eGFR (AP)

    Time frame: Baseline to Week 76

  7. Time to Onset of CRR over the Course of 76 weeks (AP)

    Time frame: Up to Week 76

  8. Percentage of Participants who Experience Treatment Failure (AP)

    Time frame: Week 12 to Week 76

  9. Change in anti-dsDNA titers (AP)

    Time frame: Baseline to Week 76

  10. Change in C3 Complement Levels (AP)

    Time frame: Baseline to Week 76

  11. Change in C4 Complement Levels (AP)

    Time frame: Baseline to Week 76

  12. Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP)

    Time frame: Baseline to Week 76

  13. Serum Concentrations of Obinutuzumab (AP)

    Time frame: Baseline to Week 76

  14. Percentage of Participants Achieving B-cell Depletion (AP)

    Time frame: Baseline, Weeks 4, 24, 52 and 76

  15. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP)

    Time frame: Baseline to Week 76

  16. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP)

    Time frame: Baseline to Week 76

  17. Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP)

    Time frame: Baseline to Week 76

  18. Percentage of Participants with Anti-drug Antibodies (ADA) (AP)

    Time frame: Weeks 0, 24, 52 and 76

  19. Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP)

    Time frame: Weeks 24, 52 and 76

  20. Percentage of Participants Achieving a CRR (PP)

    Time frame: Week 76

  21. Percentage of Participants Achieving an Overall Response (PP)

    Time frame: Week 76

    PRR is defined as achievement of all of the following:

    • >=50% reduction in UPCR from baseline
    • UPCR < 1 g/g (or < 3 g/g if the baseline UPCR was >=3 g/g)
    • eGFR >=85% of baseline
    • No occurrence of intercurrent events
  22. Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP)

    Time frame: Week 76

  23. Change in eGFR (PP)

    Time frame: Baseline to Week 76

  24. Percentage of Participants Achieving B-cell Depletion (PP)

    Time frame: Baseline, Weeks 4, 24, 52 and 76

  25. Percentage of Participants with ADAs (PP)

    Time frame: Weeks 0, 24, 52 and 76

  26. Change in anti-dsDNA titers (PP)

    Time frame: Baseline to Week 76

Study contacts

Contact information is provided by the study sponsor or research team.

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry

CONTACT

Reference Study ID Number: WA42985 https://forpatients.roche.com/ No attachments to email below.

CONTACT

[email protected]

888-662-6728 (U.S. and Canada)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • Genentech, Inc.

Registry information

Official study title

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescent Patients With Active Class III or IV Lupus Nephritis, Including an Evaluation of Open Label Safety and PK in a Cohort of Pediatric Patients (Aged 5 to < 12)

Acronym: POSTERITY

Important dates

Study start
2022
Primary completion
2028
Study completion
2030
First posted
Sep 9, 2021
Registry last updated
Jul 2, 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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