Randomized Embedded Adaptive Platform Clinical Trial in South Asian Kidney Biopsy-Proven Primary IgA Nephropathy: Multi-center, Multi-arm and Multi-stage

Status: Recruiting
Location: See all (12) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
SUMMARY

Global Burden of Diseases ranks chronic kidney disease (CKD) as the 12th leading cause of death, with an estimated 20% increase from 2010 to 2019. India is the most populous country in South Asia, with one-fourth of the global population. CKD prevalence has reached epidemic proportions in South Asia, with 1 in 7 adults affected by it. Glomerular diseases are the most common cause of CKD after diabetes and hypertension. IgAN is the most common primary glomerular disease in adults. In the Caucasian and East Asian populations, IgAN results in end-stage kidney disease (ESKD) in 15-20% of patients within 15-20 years after the first clinical presentation. Our first prospective observational (GRACE-IgANI) cohort since 2015 showed that South Asians have severe and progressive IgAN, with 39% having a rapid fall in eGFR, 25% having non-remission of proteinuria, and 36% reaching an adverse kidney outcome at three years. Our group has shown that South Asian ethnicity is associated with a severe phenotype, rapid progression, and significant ethnic differences in biomarkers. Over the last few years, newer anti-proteinuric agents and immunomodulatory drugs have either been approved by the FDA or are in the late phases of clinical trials for various proteinuric kidney diseases. The results of the STOP-IgAN and the recent TESTING trial have shown that the short-term beneficial effects of steroids on proteinuria and eGFR slope at six months wane over time, and there is a need for effective longer-term agents. The KDIGO guidelines development body on glomerular diseases has actively advocated enrolling patients prospectively in 'Clinical Trials'. Platform trials are Multi-Arm and Multi-Stage (MAMS) randomised CTs comparing multiple parallel interventional groups against standardised common control groups with central coordination. It allows new interventions to be added, the control group to be updated throughout the trial, and the use of prespecified interim analysis plans for statistical efficiencies. Interventional groups can be introduced after the trial has started based on pre-specified criteria, and futile interventions may be stopped based on pre-specified interim analyses and trial-stopping rules. This is a randomised controlled single-blind (outcome assessor) Platform trial, Multi-Arm and Multi-Stage. There is a single overarching protocol called a Master protocol. The master protocol, the common concurrent control arm for multiple interventions,the within-trial adaptations, the pre-specified interim analyses, and the pragmatic nature ensure greater acceptability and allow key trial characteristics to evolve. The overall strategy of the study relies strongly on pragmatic 'real world clinical situations' faced by practising nephrologists when treating adult patients with kidney biopsy-proven primary IgAN in South Asia. It will establish the 'GRACE Clinical Trial Network'. The overarching trial hypothesis is that commonly available and approved generic drugs (low-dose oral prednisolone, gut-directed budesonide, mycophenolate mofetil, and hydroxychloroquine) in addition to Standard of Care (SoC), which is the maximal labelled or tolerated dose of renin-angiotensin system blockers (ACEi/ ARB) and a steady dose of sodium-glucose cotransporter 2 inhibitors (SGLT2i) can significantly improve the kidney outcomes at two years when compared to Standard of Care (SoC) alone in South Asian kidney biopsy-proven adult (≥18 years) primary IgAN who on follow-up remain at high risk of progression defined as UPCR ≥0.75g/g and baseline eGFR ≥20ml/min/1.73m2 despite good BP control. SoC is defined as a maximal labelled or tolerated dose of ACEi/ ARB and a steady dose of SGLT2i with a goal BP \<140/90 mmHg for at least three months.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 65
Healthy Volunteers: f
View:

• Must be able to provide a written informed consent form, which must be obtained before the initiation of study assessments.

• Adults between 18-65 years of age.

• Males or Females.

• Diagnosis of primary IgAN as demonstrated by renal biopsy of any vintage if eGFR ≥45 mL/min/1.73 m2 or within the last ten years if eGFR \<45 mL/min/1.73 m2. If diabetic, the biopsy vintage should be less than five years.

• eGFR ≥20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

• Total urine protein excretion ≥1 g per 24-hour or UPCR ≥ 0.75 g/g from an adequately measured 24-hour urine sample (24HUP) during the Screening Period.

• Patient on the maximum labelled or tolerated dose of ACEi or ARB AND 10mg/d of Dapagliflozin (SGLT2i) for at least 12 weeks at screening and from screening to study Day 1.

• Systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg at randomisation. Other anti-hypertensives can be optimised during the screening period to achieve the BP goal.

• A female is eligible if she is not pregnant and consents to avoid pregnancy during the study duration.

Locations
Other Locations
India
AIIMS Bhubaneswar
NOT_YET_RECRUITING
Bhubaneswar
Madras Medical College
NOT_YET_RECRUITING
Chennai
Safdarjung Hospital, Ansari Nagar East
NOT_YET_RECRUITING
Delhi
Nizams Institute of Medical Sciences
NOT_YET_RECRUITING
Hyderabad
Osmania Medical College
NOT_YET_RECRUITING
Hyderabad
Sanjay Gandhi Post Graduate Institute of Medical Sciences
NOT_YET_RECRUITING
Lucknow
KEM Hospital
NOT_YET_RECRUITING
Mumbai
JSS Medical College
NOT_YET_RECRUITING
Mysuru
Muljibhai Patel Urological Hospital
NOT_YET_RECRUITING
Nadiād
JIPMER, JIPMER Campus
NOT_YET_RECRUITING
Puducherry
Kasturba Medical College, Manipal
NOT_YET_RECRUITING
Udupi
Christian Medical College Vellore
RECRUITING
Vellore
Contact Information
Primary
Suceena Alexander, DM, PhD.
suceena@cmcvellore.ac.in
+91-417-
Backup
Selvin Sundar Raj, MD, DM
selvinsr@cmcvellore.ac.in
+91-417-
Time Frame
Start Date: 2025-02-15
Estimated Completion Date: 2029-08
Participants
Target number of participants: 585
Treatments
Active_comparator: Standard of Care (SoC)
This intervention arm will start with the randomisation of the first participant.
Experimental: SoC and Oral prednisolone
This intervention arm will start with randomisation of the first participant.
Experimental: SoC and Gut-directed budesonide
This intervention arm will start with the randomisation of the first participant.
Experimental: SoC and Mycophenolate mofetil (MMF)
This intervention arm will start with the randomisation of the first participant.
Experimental: SoC and Hydroxychloroquine
This intervention arm will start with the randomisation of the first participant.
Experimental: SoC and Non-steroidal mineralocorticoid receptor antagonist
The sixth arm may begin after the planned interim analysis conditional to the availability of the generic drug in the Indian market and will recruit an additional 117 participants with a concurrent comparator arm.
Sponsors
Collaborators: Medical Research Council, India Alliance
Leads: Christian Medical College, Vellore, India

This content was sourced from clinicaltrials.gov