CTRI/2023/11/059398 [Registered on: 01/11/2023] Trial Registered Prospectively
Last Modified On:
09/05/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A Phase 3 clinical trial of Atacicept in Subjects with IgA Nephropathy
Scientific Title of Study
A Phase 2b/3, Multi-part, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in Subjects with IgA Nephropathy (IgAN)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
2020-004892-41
EudraCT
NCT04716231
ClinicalTrials.gov
VT-001-0050
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Supriya Parui
Designation
Regulatory Submission CoordinatorÂ
Affiliation
Medpace Clinical Research India Pvt. Ltd
Address
Unit Number 1203, 12th Floor, Bldg.Q2, Aurum Q2 Parc, Gen 4/1, TTC, Thane Belapur Road, Navi Mumbai
Thane MAHARASHTRA 400710 India
Phone
9773922367
Fax
Email
s.parui@medpace.com
Details of Contact Person Public Query
Name
Supriya Parui
Designation
Regulatory Submission CoordinatorÂ
Affiliation
Medpace Clinical Research India Pvt. Ltd
Address
Unit Number 1203, 12th Floor, Bldg.Q2, Aurum Q2 Parc, Gen 4/1, TTC, Thane Belapur Road, Navi Mumbai
Thane MAHARASHTRA 400710 India
Phone
9773922367
Fax
Email
s.parui@medpace.com
Source of Monetary or Material Support
Vera Therapeutics, Inc.
Primary Sponsor
Name
Vera Therapeutics, Inc.
Address
8000 Marina Boulevard, Suite 120
Brisbane, CA 94005
United States of America
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Belgium Brazil Canada China Croatia Czech Republic Denmark Estonia France Germany Greece Hong Kong India Ireland Italy Japan Malaysia Philippines Poland Portugal Republic of Korea Singapore Spain Sri Lanka Taiwan Thailand Turkey United Kingdom United States of America
Department of Nephrology,
Kilminnal Village, Ranipet District, Tamil Nadu - 632517, India Vellore TAMIL NADU
9894519136
suceena@gmail.com
Dr Ashok Kumar Sharma
Eternal Hospital, Jaipur A unit of Eternal Heart Care Centre & Research Institute Pvt. Ltd
Dept of Nephrology, Ground floor, 3A, Jagatpura Road, Near Jawahar Circle, Rajasthan, Jaipur-302017 Jaipur RAJASTHAN
9829065210
research@eternalheart.org
Dr Atanu Pal
IPGMER & SSKMH
Dept of Nephrology, Ground floor room 30, clinical research room, 244 AJC Bose Road, Kolkata-700020, West Bengal, India Kolkata WEST BENGAL
9038080051
dratanup@gmail.com
Dr Pradeep Shenoy
Justice KS Hegde Charitable Hospital, Karnataka
Nephrology Department, 3rd Floor, clinical research room, Deralakatte, Mangalore University Road, Mangalore, Karnataka- 575018 Dakshina Kannada KARNATAKA
9844546066
pshenoynephro@gmail.com
Dr Sunil R
Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bangalore (KIMS),
Department of Nephrology, Clinical research room, B block, 1st floor, Next to dialysis unit, next K R Road, V V Puram, Bangalore - 560004, India Bangalore KARNATAKA
9986633848
drsunilrg@gmail.com
Dr Prakash Khetan
KIMS-Kingsway hospital, Nagpur
Dept of Nephrology, 44, Kingsway Hospital, Near Kasturchand Park, Nagpur- 440001, Maharashtra, India Nagpur MAHARASHTRA
9823071748
prakash.khetan@kingswayhospitals.com
Dr Ritesh Vernekar
KLE’s Dr Prabhakar Kore Hospital & Medical Research Centre
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Dept of Nephrology, New PMSSY Rd, Raibareli Rd, Lucknow,
Uttar Pradesh 226014 Lucknow UTTAR PRADESH
9918810550
drmrpnephro@gmail.com
Dr Vivek Ruhela
Shri Mahant Indiresh Hospital, Dehradun
North Block (new building), 03rd floor, Nephrology OPD, ART Centre, room no 02, Kargi - Patel Nagar Bypass, Industrial Area, Govt. Industrial Estate, Patel Nagar, Dehradun, Uttarakhand 248001 Dehradun UTTARANCHAL
9721104868
vivekruhela@yahoo.com
Dr Sonal Dalal
Sterling Hospital, Ahmedabad Sterling Hospital – A unit of Sterling Addlife India Pvt. Ltd.,
Dept of Nephrology, Clinical Research Dept, 2nd floor, Sterling Hospital Road, Memnagar – 380 052, Ahmedabad, Gujarat, India Ahmadabad GUJARAT
9825008924
sonalsanjiv@yahoo.com
Dr Kalpana Mehta
T.N.M.C & B.Y.L Nair Hospital
Department of Nephrology, 7th Floor, OPD Building, Dr. A. L, Dr Anandrao Nair Marg, RTO Colony, Mumbai Central, Mumbai 400008, Maharashtra, India Mumbai MAHARASHTRA
9322226090
kalpana.drs@gmail.com
Dr Sandeep Morkhandikar
WMF’s Villoo Poonawalla Memorial Hospital
S.No 156, Soli Poonawalla Road,
Pune-Solapur Road, Hadapsar, Pune,
Maharashtra – 411028, India Pune MAHARASHTRA
(1) ICD-10 Condition: N29||Other disorders of kidney and ureter in diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
AtaciceptÂ
Part C: Atacicept 150mg will be administered as once weekly subcutaneous (SC) injections to IgAN participants over the course of 104 weeks. Part D: Atacicept 150mg will be administered as once weekly subcutaneous (SC) injection to IgAN participants over the course of 52 weeks.
Comparator Agent
Placebo
Placebo to match Atacicept (Part C) formulation contains trehalose and sodium acetate buffer (pH 5.0), will be administered as once weekly subcutaneous (SC) injections to IgAN participants over the course of 104 weeks.
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study assessments.
2. Adult male or female of greater than equal to 18 years of age and less than equal to 70 years, or as per country specific legally or nationally recognized adult age, who provide written informed consent prior to performing any study assessments.
3. Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years of the Screening Visit.
4. Total urine protein excretion >0.75g per 24-hour or urine protein to creatinine ratio (UPCR) >0.75 mg/mg based on a 24-hour urine sample during the Screening Period
5. eGFR greater than equal to 30 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
6. On a stable prescribed regimen of RAASi for at least 12 weeks that is at the maximum labeled or tolerated dose at screening
a. The subject is eligible if they do not tolerate RAASi, provided their management of IgAN is standard of care (SoC) according to local guidelines. This must be documented by the Investigator
7. Systolic blood pressure less than equal to 150 mmHg and diastolic blood pressure less than equal to 90 mmHg at screening
8. A female is eligible if she is not pregnant (i.e., after a confirmed menstrual period, a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1), not breastfeeding (for at least 3 months prior to screening), and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP)
b. Is a WOCBP who agrees to use a highly effective contraceptive method (i.e., has a failure rate of less than 1% per year), at least 7 days prior to randomization, through 175 days after the last dose of study drug.
ExclusionCriteria
Details
1. Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept
2. IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis
3. Evidence of rapidly progressive glomerulonephritis (loss of ≥ 50% of eGFR within 3 months of screening)
4. Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR >3.5 mg/mg)
5. Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants.
6. Concomitant chronic renal disease in addition to IgAN (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy, C3 glomerulopathy, lupus nephritis)
7. Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening
8. History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test at the Screening Visit.
If the subject is undergoing current treatment for LTBI, they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to the Screening Visit without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening Visit, the subject will be expected to complete an appropriate LTBI treatment regimen to remain in the trial.
a. Subjects with current household contacts with active TB will be excluded unless prophylaxis treatment has been completed, and evidence that household contacts have completed treatment is provided.
b. Indeterminate Quantiferon tests may be repeated once by the same test and will be considered positive if retest results are positive or indeterminate.
9. Prohibited medications:
Use of systemic corticosteroids (including oral budesonide) for the treatment of IgAN within 6 months prior to screening, from screening to Day 1 or expected use during the study.
• For glucocorticosteroids (GCS), “Systemic†is defined as oral, rectal or injectable (intravenous or intramuscular) routes of administration. Other routes of administration are allowed, including intra-articular, inhaled, topical, ophthalmic, otic and intranasal.For non-IgAN indications (e.g., gout flare, exacerbation of asthma, severe rash, etc.):
− Within 12 weeks prior to randomization: Use of systemic corticosteroids or immunosuppressive medications for >1 week or average dose >0.5 mg/kg/day prednisolone or equivalent
• Immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 12 weeks prior to screening, from screening to Day1 or expected use during the study.
• Use of traditional Chinese medications and/or Ayurvedic medications within 12 weeks prior to screening or from screening to Day 1
• Use of B-cell–directed biologic therapies including but not limited to belimumab, rituximab, ocrelizumab for any period of time
• Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics for any period of time
• Use of endothelin receptor antagonists (ERAs) for any period of time
10. Clinically significant or predefined abnormalities per central laboratory tests, at the Screening Visit, meeting any of the criteria below:
• serum IgG below 7 g/L
• aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level >2.5 × upper limit of normal (ULN) or total bilirubin >1.5 x ULN.
i. If subject has a known history of Gilberts (history of isolated increase in total bilirubin without increase in liver transaminases), contact the Medical Monitor for further discussion.
• hemoglobin <10 g/100 mL in men and hemoglobin <9 g/100 mL in women
• platelets <100,000/L mm3
11. Administration of live and live-attenuated vaccinations within 30 days prior to randomization
12. History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON)
13. Patients with history of unstable angina, Class III and IV congestive heart failure and/or clinically significant arrhythmia, as judged by the Investigator.
14. Any condition, including any uncontrolled disease state other than IgAN, that in the opinion of the Investigator or the Sponsor/designee constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
15. Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to, or during the Screening Visit, or completion of oral anti-infectives within 2 weeks prior to, or during the Screening Visit or a history of recurrent infections (i.e., 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary.
16. History of acute or chronic infection with human immunodeficiency virus, or hepatitis B virus.
• Subjects with positive hepatitis B surface antigen (HBsAg) are excluded
• Subjects who are HBsAg negative, hepatitis B core antibody (HBcAb) positive, hepatitis B surface antibody (HBsAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring through safety follow-up
17. Subjects with positive hepatitis C (HCV) RNA are excluded, however, subjects who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
18. History of splenectomy
19. History of malignancy (hematologic or solid tumor) within 5 years prior to Screening Visit, except adequately treated basal cell or squamous cell carcinomas of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.
20. Known hypersensitivity to atacicept or any component of the formulated atacicept
21. Major surgery within 6 weeks prior to the Screening Visit or planned/expected major surgery during the study period (including the Safety Follow-up Period)
• Major surgery often involves opening one of the major body cavities (abdomen, chest, and skull) and/or use of general anesthesia. Types of surgery that have the highest risk include heart or lung, liver, abdomen, or major operations on the bones and joints (for example, hip replacement)
22. Clinically significant history of alcohol or drug abuse in the 1 year prior to the Screening Visit as per Investigator opinion
23. Unwillingness or lack of capacity to follow all study procedures
24. Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to the Screening Visit.
Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgAN using a mixed-effects model repeated measures (MMRM) analysis of Urine protein to creatinine ratio (UPCR)
Key Secondary: Evaluate the effect of atacicept on annualized rate of change in estimated glomerular filtration rate (eGFR) using MMRM analysis of Annualized Rate of change in eGFR (ie., annualized eGFR total slope)
Through Week 104
Secondary: Evaluate the effect of atacicept compared to placebo on change in Gd-IgA1
Weeks 36, 52, & 104
Secondary: Evaluate the effect of atacicept on annualized rate of change in eGFR sing MMRM analysis of Annualized Rate of change in eGFR (ie., annualized eGFR total slope)
Week 52
Secondary: Time from randomization to first occurrence of composite kidney failure endpoint event
Composite kidney failure endpoint defined as experiencing at least one of the following during the study:
• At least a 30% reduction in eGFR sustained for at least 30 days
• eGFR 15 mL/min/1.73m2, sustained for at least 30 days
• Chronic dialysis greater than equal to 30 days
• Kidney transplantation
• Death
Through the end of double-blinded period.
Target Sample Size
Total Sample Size="376" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This Phase 3 study will evaluate the efficacy and safety of the planned commercial dose of atacicept (150 mg) compared to placebo in reducing proteinuria in subjects with IgAN and persistent proteinuria despite being on a maximally tolerated dose (MTD) of a RASi. High risk of progression in IgAN is currently defined as proteinuria >0.75-1 g/d despite optimized supportive care (International Society of Nephrology 2021).
Atacicept is capable of binding to all known conformations of BLyS and APRIL and is thus expected to inhibit the maturation, differentiation, and effector function of B cells. These mechanisms are consistent with the known pharmacological effects of atacicept, which include depletion of peripheral B cell subsets, naïve follicular, marginal zone and long lived plasma cell B cell subsets, impeded germinal center reaction, and reduced immunoglobulins, while leaving immature B cells and memory B cells intact (Dillon 2006, Dillon 2010, Gross 2001, Moore 1999, Schneider 1999, Schneider 2005). These effects are predicted to reduce the production and subsequent deposition of Gd-IgA1-containing immune complexes in kidney glomeruli, and thus reduce the extent of kidney injury in IgAN patients.
This is a multi-part study comprising of the original Phase 2b study and the addition of a separate Phase 3 study. A Phase 3 study (i.e., Parts C and D) has been added as a separate component of the existing study to obtain study operational efficiency by keeping the original sites activated and modifying existing study systems and plans. The results from the Phase 2b parts have been used to determine the dose selection and sample size for the Phase 3 study design.
The Phase 3 study is a multicenter, randomized, double-blind, placebo-controlled trial. In Part C, subjects will be randomized 1:1 to atacicept 150 mg or placebo for 104 weeks:
• Atacicept 150 mg once weekly subcutaneous (SC) injections (N=188)
• Placebo once weekly subcutaneous (SC) injections (N=188)
Followed by a 52-week open-label extension (Part D) in which subjects will be given 150 mg atacicept once weekly subcutaneous (SC) injections.