Health TrialsbyHealthPanel

Infliximab for Immune Checkpoint Inhibitor Associated AKI

ConditionsAcute Kidney InjuryAcute Interstitial Nephritis
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorMassachusetts General Hospital

About this trial

This is a multi-center, 1:1 randomized pilot study examining the efficacy and safety of infliximab 5mg/kg x 1 paired with 2 weeks of prednisone 1mg/kg per day for 2 weeks versus standard-of-care glucocorticoid therapy (prednisone 1mg/kg/day x 2 weeks followed by a 4 week taper) on the rate and speed of renal recovery from immune checkpoint inhibitor-associated AKI.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years.

Acute kidney injury (AKI), defined as ≥1.5-fold increase in serum creatinine compared to baseline. Baseline is defined as the closest serum creatinine value prior to immune checkpoint inhibitor initiation (ICI).

Receipt of ICI in the 180 days preceding AKI onset.

AKI due to ICI-AIN, based on either a kidney biopsy or clinical adjudication by the treating team.

Disqualifiers

Any condition requiring high dose glucocorticoids (GCs) (>10 mg/day prednisone equivalents) or other immunosuppressants, such as infliximab, tocilizumab, mycophenolate mofetil, B cell depletion, or calcineurin inhibitors, within 14 days preceding screening

Evidence of any uncontrolled infection, including Tuberculosis (must have no evidence of active or latent TB determined by clinical history and negative interferon gamma release assay within the last 12 months or at screening); Hepatitis B (based on AntiSAg and HBV DNA negative within the last 12 months or at screening. Patients with Isolated Anti-HBcore positivity must agree to antiviral prophylaxis with entecavir for 6 months after receiving infliximab); Hepatitis C (must have no uncontrolled active infection evidenced by negative HCV antibody or HCV RNA within the last 12 months or at screening, and reflex testing must be performed for any patient with HCV antibody positivity); Patients with known HIV must be on stable disease antiretroviral therapy ≥12 weeks with a negative viral load [<50 copies/mL] at screening and CD4 count ≥ 350 cells/uL) measured within the last 12 months.

History of hypersensitivity to infliximab or murine proteins.

Moderate-severe (New York Heart Association class III/IV) heart failure or recent decompensation.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Infliximab

    Drug

    Infliximab 5mg/kg x 1 and prednisone 1mg/kg per day (rounded to the nearest 10mg) x 2 weeks

  • Prednisone

    Drug

    Prednisone 1mg/kg per day for 2 weeks (rounded to the nearest 10mg, maximum 100mg/day) followed by a 4-week taper, tapered by 0.2mg/kg/day per week.

  • prednisone (oral)

    Drug

    Prednisone 1mg/kg per day for two weeks (Rounded do the nearest 10mg and maximum dose of 100mg per day)

Treatment groups

44 Participants
are divided into 2 treatment groups
Group A: InfliximabExperimental treatment 2 interventions
Group B: Prednisone per standard of careActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Acute kidney injury recovery at 12 weeks

The proportion of patients achieving AKI recovery within 12 weeks is defined as return of serum creatinine to less than 1.5-fold baseline creatinine within the need for ongoing immunosuppression. (Active immunosuppression is defined as currently receiving \>10mg/day of prednisone equivalent or having received any non-glucocorticoid immunosuppressant within the last 2 weeks).

Time frame
12 weeks

Secondary outcomes

1

Time to AKI recovery

Time to AKI recovered is defined as the time in days to meeting criteria for AKI recovery as defined in the primary outcome.

Time frame
24 weeks
2

Time to ICI-AKI recurrence

Time to ICI-AKI recurrence is defined as \>= 1.5-fold rise in serum creatinine compared to the lowest serum creatinine achieved while receiving immunosuppression, occurring within 24 weeks following randomization and without a clear alternative more likely cause of AKI.

Time frame
24 weeks
3

Change in serum creatinine

Change from enrollment to follow-up serum creatinine

Time frame
24 weeks
4

Tumor response

Tumor response is determined using the RECIST 1.1 criteria, a widely accepted 4-category scale (complete response, partial response, stable disease, and disease progression).

Time frame
24 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Massachusetts General Hospital

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov
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