A Rollover Study to Evaluate the Long-Term Safety and Efficacy of Atacicept

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vera Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

28 Feb 2025 → ongoing

Decision date (initial)

2025-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Vera Therapeutics, Inc.

External identifiers

EU CT number

2024-516380-81-00

WHO UTN

U1111-1309-3762

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To evaluate the long-term safety and tolerability of atacicept.

Secondary objectives 1

1. 1. To evaluate the long-term efficacy of atacicept.

Conditions and MedDRA coding

Treatment of IgAN

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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. 2. Completed the protocol-defined treatment period on treatment in a parent study of atacicept in patients with IgAN.
3. 3. For Atacicept Drug Holiday Group only: Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg at screening and Day 1.
4. 4. A participant who was assigned female at birth is eligible if not pregnant (ie, after a confirmed menstrual period, a negative serum pregnancy test at screening and has a negative urine pregnancy test at Day 1), is not breastfeeding (for at least three months prior to screening), and at least one of the following conditions applies: *Is not a woman of childbearing potential (WOCBP) OR *Is a WOCBP who agrees to use a highly effective contraceptive method (ie, has a failure rate of less than 1% per year) at least 7 days prior to enrollment, through 175 days after the last dose of study drug.
5. 5. For Atacicept Drug Holiday Group only: eGFR ≥ 20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
6. 6. For Atacicept Drug Holiday Group only: On a stable prescribed regimen of renin-angiotensin-aldosterone system inhibitor (ACEi or ARB) per guidance and local standard of care that is at the maximum labeled or tolerated dose at screening and from screening to study Day 1.

Exclusion criteria 28

1. 1. For Group 1 Atacicept Drug Holiday: Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months of screening).
2. 2. For Group 1 Atacicept Drug Holiday: Evidence of nephrotic syndrome (serum albumin <30g/L in association with UPCR >3.5 mg/mg) within 6 months of screening.
3. 3. For Group 1 Atacicept Drug Holiday: Currently on chronic dialysis, or expected to initiate dialysis within 12 weeks of screening.
4. 4. For Group 1 Atacicept Drug Holiday: Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants.
5. 5. For Group 1 Atacicept Drug Holiday: Prohibited medications: • Use of systemic corticosteroids (including oral budesonide) or immunosuppressive medications (eg, MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 2 months prior to Screening • 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, optic and intranasal. • Use of B-cell–directed biologic therapies including belimumab, rituximab, ocrelizumab within 12 months of screening • Use of other biologics (eg, anti-TNF, abatacept, anti-IL-6) and investigational biologics for the treatment of IgAN within 6 months of screening
6. 6. For Group 1 Atacicept Drug Holiday: Clinically significant or predefined abnormalities per central laboratory tests at screening, meeting any of the criteria below: - Clinical evidence of immunosuppression and/or hypogammaglobulinemia as determined by the Investigator. - Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level >2.5 × upper limit of normal (ULN) or total bilirubin >1.5 x ULN. *If the participant 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.
7. 7. For Group 1 Atacicept Drug Holiday: Administration of live and live-attenuated vaccinations within 30 days prior to enrollment
8. 8. For Group 1 Atacicept Drug Holiday: History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON)
9. 9. For Group 1 Atacicept Drug Holiday: 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 enrollment, or completion of oral anti-infectives within 2 weeks prior to enrollment, or a history of recurrent infections (ie, 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. • If the participant is undergoing current treatment for latent tuberculosis infection (LTBI), they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to screening without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening visit, the participant will be expected to complete an appropriate LTBI treatment regimen to remain in the trial. • Participants 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. • Evidence of active TB determined by a local laboratory at the Screening Visit. Indeterminate local TB tests may be repeated once by the same test and will be considered positive if retest results are positive or indeterminate.
10. 10. For Group 1 Atacicept Drug Holiday: History of acute or chronic infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus. • Participants who are positive hepatitis B surface antigen (HBsAg) are excluded • Participants 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. • Participants with positive hepatitis C (HCV) RNA are excluded, however participants who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
11. 11. For Group 1 Atacicept Drug Holiday: History of splenectomy.
12. 12. For Group 1 Atacicept Drug Holiday: History of malignancy (hematologic or solid tumor) within 5 years prior to Day 1, 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
13. 13. For Group 1 Atacicept Drug Holiday: Known hypersensitivity to atacicept or any component of the formulated atacicept
14. 14. For Group 1 Atacicept Drug Holiday: Major surgery within 6 weeks prior to screening 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 or chest) 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 (eg, hip replacement). Participants with positive hepatitis C (HCV) RNA are excluded, however participants who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
15. 15. For Group 1 Atacicept Drug Holiday: Clinically significant history of alcohol or drug abuse in the 1 year prior to Day 1 as per Investigator opinion
16. 16. For Group 1 Atacicept Drug Holiday: Unwillingness or lack of capacity to follow all study procedures
17. 17. For Group 1 Atacicept Drug Holiday: Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to screening
18. 18. For Group 1 Atacicept Drug Holiday: Total urine protein excretion ≥5g per 24-hour or UPCR ≥5 mg/mg based on a 24-hour urine sample during the Screening Period
19. 19. For Group 1 Atacicept Drug Holiday: Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening
20. 20. For Group 2 Continuous Atacicept: Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months of Day 1)
21. 21. For Group 2 Continuous Atacicept: Evidence of nephrotic syndrome (serum albumin <30g/L in association with UPCR >3.5 mg/mg) within 6 months of Day 1
22. 22. For Group 2 Continuous Atacicept: Currently on chronic dialysis, or expected to initiate dialysis within 12 weeks of Day 1
23. 23. For Group 2 Continuous Atacicept: Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants
24. 24. For Group 2 Continuous Atacicept: Clinically significant or predefined abnormalities per central laboratory tests on Day 1 , meeting any of the criteria below: • Clinical evidence of immunosuppression and/or hypogammaglobulinemia as determined by the Investigator
25. 25. For Group 2 Continuous Atacicept: 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 enrollment, or completion of oral anti-infectives within 2 weeks prior to enrollment, or a history of recurrent infections (ie, 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.
26. 26. For Group 2 Continuous Atacicept: Known hypersensitivity to atacicept or any component of the formulated atacicept
27. 27. For Group 2 Continuous Atacicept: Clinically significant history of alcohol or drug abuse in the one year prior to Day 1 as per Investigator opinion
28. 28. For Group 2 Continuous Atacicept: Unwillingness or lack of capacity to follow all study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Long-term safety and tolerability of atacicept as assessed by routine clinical and laboratory tests and adverse events

Secondary endpoints 1

1. The effect of atacicept on the following: *Changes in proteinuria based on UPCR and UACR as determined by spot urine. *Changes in estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C, respectively. *Hematuria level based on blood on urine dipstick. *Changes in serum Gd-IgA1 levels.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vera Therapeutics Inc.

Sponsor organisation

Vera Therapeutics Inc.

Address

2000 Sierra Point Parkway Suite 1200

City

Brisbane

Postcode

94005-1806

Country

United States

Scientific contact point

Organisation

Vera Therapeutics Inc.

Contact name

Regulatory

Public contact point

Organisation

Vera Therapeutics Inc.

Contact name

Regulatory

Third parties 7

Locations

6 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications