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 |
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Recruitment Status :
Recruiting
First Posted : September 9, 2021
Last Update Posted : June 22, 2022
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Sponsor:
Hoffmann-La Roche
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
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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 |
| 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 |
| Actual Study Start Date : | May 12, 2022 |
| Estimated Primary Completion Date : | March 28, 2025 |
| Estimated Study Completion Date : | March 13, 2027 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Obinutuzumab
| Arm | Intervention/treatment |
|---|---|
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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).
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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. |
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Placebo Comparator: Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
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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 :
- 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 :
- Percentage of Participants Achieving a CRR [ Time Frame: Weeks 24 and 52 ]
- Percentage of Participants who Achieve a Partial Renal Response (PRR) [ Time Frame: Week 76 ]
- 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
- Change in UPCR [ Time Frame: Baseline to Week 76 ]
- Change in eGFR [ Time Frame: Baseline to Week 76 ]
- Time to Onset of CRR over the Course of 76 weeks [ Time Frame: Up to Week 76 ]
- Percentage of Participants who Experience Treatment Failure [ Time Frame: Week 12 to Week 76 ]
- Change in C3 Complement Levels [ Time Frame: Baseline to Week 76 ]
- Change in C4 Complement Levels [ Time Frame: Baseline to Week 76 ]
- 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 ]
- Serum Concentrations of Obinutuzumab [ Time Frame: Baseline to Week 76 ]
- Percentage of Participants Achieving B-cell Depletion via Highly Sensitive Flow Cytometry (HSFC) [ Time Frame: Baseline, Weeks 4, 24, 52 and 76 ]
- Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score [ Time Frame: Baseline to Week 76 ]
- Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [ Time Frame: Baseline to Week 76 ]
- Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores [ Time Frame: Baseline to Week 76 ]
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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
| Contact: Reference Study ID Number: WA42985 https://forpatients.roche.com/ | 888-662-6728 (U.S. and Canada) | global.rochegenentechtrials@roche.com |
Locations
Show 20 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| 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: | June 22, 2022 |
| Last Verified: | June 2022 |
| 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). |
| 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 |