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Monoclonal Antibodies

Belimumab + Rituximab for Kidney Disease (REBOOT Trial)

Phase 2

Recruiting

Research Sponsored by National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Serum anti-PLA2R positive

Proteinuria ≥ 4 and < 8 g/day that has persisted for at least the previous 3 months while on maximally tolerated RAS blockade

Must not have

Unstable kidney function defined as > 20% decrease in eGFR during the previous 3 months due to primary MN

Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until week 104

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 4, week 12, week 24, week 36, week 52

Awards & highlights

All Individual Drugs Already Approved

Summary

This trial will enroll approximately 30 participants with primary MN who are not well controlled with their current therapy. Participants will be randomly assigned (by chance, like flipping a coin) to one of two treatment groups.

Who is the study for?

Adults aged 18-75 with primary membranous nephropathy, confirmed by kidney biopsy within the last 5-7 years, and experiencing significant protein loss in urine despite treatment. Participants must have a stable kidney function and blood pressure under control. They should be vaccinated against COVID-19 as per CDC guidelines. Pregnant or breastfeeding women, recent recipients of certain immunosuppressants or live vaccines, and those with various health complications are excluded.

What is being tested?

The trial is testing if belimumab combined with rituximab can induce complete remission in primary membranous nephropathy more effectively than rituximab alone. Belimumab may reduce new B cells that cause immune attacks on kidneys; neither drug is currently FDA-approved for this condition.

What are the potential side effects?

Potential side effects include reactions to infusions, infections due to weakened immunity, blood cell count changes (like anemia), liver enzyme elevations indicating potential liver damage, allergic reactions to medication components, and possibly others not listed here.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My blood test is positive for anti-PLA2R antibodies.

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I have had protein in my urine between 4 and 8 g/day for the last 3 months despite treatment.

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My blood pressure is 140 or lower with my current medication.

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I am losing more than 8 grams of protein a day in my urine despite taking medication.

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I have nephrotic syndrome and cannot undergo a kidney biopsy.

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My kidney function is adequate while on specific blood pressure medication.

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My lowest blood pressure number is 90 or less, even with my current medication.

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I am between 18 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function has dropped by more than 20% in the last 3 months due to my kidney disease.

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I am not pregnant, nursing, and willing to use contraception or abstain from sex until week 104.

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My diabetes is not well-managed, with an HbA1c level of 9.0% or higher.

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I haven't had cancer in the last 5 years, except for skin cancer.

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I have lung disease with reduced lung function or need extra oxygen.

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I have not received a live vaccine in the last 30 days.

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My kidney biopsy shows I have advanced diabetic kidney damage.

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I have not taken Cyclophosphamide in the last 3 months.

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I have not had cancer screenings recommended for my age.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 4, week 12, week 24, week 36, week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 4, week 12, week 24, week 36, week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 4, week 12, week 24, week 36, week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of Participants in Complete or Partial Remission (CR or PR) at Week 104.

Secondary study objectives

Incidence of Arterial Thromboembolic Events: By Treatment Group

Incidence of Grade 3 or Higher Infectious Adverse Events (AEs): By Treatment Group

Incidence of Venous Thromboembolic Events: By Treatment Group

Other study objectives

EXPLORATORY: Belimumab Levels at Week 4, Week 12, Week 24, Week 36 and Week 52

Side effects data

From 2018 Phase 3 trial • 80 Patients • NCT02119156

36%

Nasopharyngitis

18%

Hypokalaemia

Cystitis

Gastroenteritis

Periodontal disease

Joint injury

Vertigo

Ocular discomfort

Lumbar vertebral fracture

Upper respiratory tract infection

Dental caries

Musculoskeletal chest pain

Cough

Otitis externa bacterial

100%

80%

60%

40%

20%

Study treatment Arm

Treatment Phase: Treatment Holiday Group - Re-start Phase

Maintenance Phase: Treatment Holiday

Treatment Phase: Long-term Discontinuation Group

Treatment Phase: Treatment Control Group

Treatment Phase: Treatment Holiday Group - Holiday Phase

Maintenance Phase: Treatment Control

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Part B: Belimumab and RituximabExperimental Treatment2 Interventions

Participants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive subcutaneous belimumab 400 mg (two 200 mg injections) once weekly from weeks 0-3, and then 200 mg once weekly from weeks 4-51. Participants will receive rituximab infusions at Weeks 4 and 6. At week 30, participants will be assessed for a response to study treatment. Participants who meet at least two out of the following three criteria at week 30 will be considered to have an inadequate response to study treatment and receive a second course of rituximab (defined as 1000 mg IV given at weeks 34 and 36): * Anti-PLA2R level is ≥ 25% of baseline * Proteinuria is ≥ 50% of baseline * Serum albumin is \< 2.8 g/dL

Group II: Part A: Low Proteinuria Group - Belimumab and RituximabExperimental Treatment2 Interventions

Open-label pharmacokinetics (PK) phase. Participants with low proteinuria classification will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6. Low proteinuria classification: The excretion of ≥4 to \<8 g/day of protein by the kidneys in adults. (Normal in adults: 0.15 g/day).

Group III: Part A :High Proteinuria Group - Belimumab and RituximabExperimental Treatment2 Interventions

Open-label pharmacokinetics (PK) phase. Participants with high proteinuria classification will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6. High proteinuria classification: The excretion of ≥8 g/day of protein by the kidneys in adults. (Normal in adults: 0.15 g/day).

Group IV: Part B: Placebo and RituximabPlacebo Group2 Interventions

Participants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive subcutaneous belimumab placebo 400 mg (two 200 mg injections) once weekly from weeks 0-3, and then 200 mg once weekly from weeks 4-51. Participants will receive rituximab infusions at Weeks 4 and 6. At week 30, participants will be assessed for a response to study treatment. Participants who meet at least two out of the following three criteria at week 30 will be considered to have an inadequate response to study treatment and receive a second course of rituximab (defined as 1000 mg IV given at weeks 34 and 36): * Anti-PLA2R level is ≥ 25% of baseline * Proteinuria is ≥ 50% of baseline * Serum albumin is \< 2.8 g/dL

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Rituximab

FDA approved

Belimumab

FDA approved

0 / 17Eligibility criteria met