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A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis (POSTERITY)

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ClinicalTrials.gov Identifier: NCT05039619
Recruitment Status : Recruiting
First Posted : September 9, 2021
Last Update Posted : November 26, 2021
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics of obinutuzumab in adolescent participants aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: Obinutuzumab Drug: Placebo Drug: Mycophenolate Mofetil Drug: Acetaminophen/paracetamol Drug: Diphenhydramine hydrochloride (HCl) Drug: Methylprednisolone Drug: Prednisone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Estimated Study Start Date : December 30, 2021
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : March 13, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
Drug: Obinutuzumab
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 Name: Gazyva

Drug: Mycophenolate Mofetil
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.

Drug: Acetaminophen/paracetamol
Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.

Drug: Diphenhydramine hydrochloride (HCl)
Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.

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

Drug: Prednisone
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.

Placebo Comparator: Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
Drug: Placebo
Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.

Drug: Mycophenolate Mofetil
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.

Drug: Acetaminophen/paracetamol
Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.

Drug: Diphenhydramine hydrochloride (HCl)
Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.

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

Drug: Prednisone
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 Outcome Measures :
  1. Percentage of Participants who Achieve a Complete Renal Response (CRR) [ Time Frame: Week 76 ]

    CRR is defined as achievement of all of the following:

    • Urinary protein-to-creatinine ratio (UPCR) <0.5
    • Estimated Glomerular Filtration Rate (eGFR) >=85% of baseline
    • No occurrence of intercurrent events


Secondary Outcome Measures :
  1. Percentage of Participants Achieving a CRR [ Time Frame: Weeks 24 and 52 ]
  2. Percentage of Participants who Achieve a Partial Renal Response (PRR) [ Time Frame: Week 76 ]
  3. Percentage of Participants Achieving an Overall Response (CRR or PRR) [ 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 (or < 3 if the baseline UPCR was >=3)
    • eGFR >=85% of baseline
    • No occurrence of intercurrent events

  4. Change in UPCR [ Time Frame: Baseline to Week 76 ]
  5. Change in eGFR [ Time Frame: Baseline to Week 76 ]
  6. Time to Onset of CRR over the Course of 76 weeks [ Time Frame: Up to Week 76 ]
  7. Percentage of Participants who Experience Treatment Failure [ Time Frame: Week 12 to Week 76 ]
  8. Change in C3 Complement Levels [ Time Frame: Baseline to Week 76 ]
  9. Change in C4 Complement Levels [ Time Frame: Baseline to Week 76 ]
  10. Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: Baseline to Week 76 ]
  11. Serum Concentrations of Obinutuzumab [ Time Frame: Baseline to Week 76 ]
  12. Percentage of Participants Achieving B-cell Depletion via Highly Sensitive Flow Cytometry (HSFC) [ Time Frame: Baseline, Weeks 4, 24, 52 and 76 ]
  13. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score [ Time Frame: Baseline to Week 76 ]
  14. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [ Time Frame: Baseline to Week 76 ]
  15. Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores [ Time Frame: Baseline to Week 76 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05039619


Contacts
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Contact: Reference Study ID Number: WA42985 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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United States, Louisiana
Louisiana State University Recruiting
Shreveport, Louisiana, United States, 71103
United States, New York
Cohen Children's Medical Center of New York; Pediatrics Recruiting
Queens, New York, United States, 11042
Poland
Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii Recruiting
Torun, Poland, 87-100
South Africa
Red Cross War Memorial Children's Hospital; Nephrology Unit Withdrawn
Cape Town, South Africa, 7700
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05039619    
Other Study ID Numbers: WA42985
2021-000097-29 ( EudraCT Number )
First Posted: September 9, 2021    Key Record Dates
Last Update Posted: November 26, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Acetaminophen
Diphenhydramine
Promethazine
Mycophenolic Acid
Prednisone
Methylprednisolone
Obinutuzumab
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antipyretics
Antibiotics, Antineoplastic
Antibiotics, Antitubercular