The Clinical Trial of ADR-001 for IgA Nephropathy

Open-label, Multiple-center, Dose-Escalation Study to Evaluate the Safety and Tolerability of ADR-001 for the Treatment for Immunoglobulin A (IgA) Nephropathy

The purpose of this study is to evaluate the safety and the tolerability of ADR-001 in Immunoglobulin A (IgA) Nephropathy patients. In addition, the investigators will evaluate the efficacy of ADR-001 for IgA Nephropathy patients.

Study Overview

• Status: Completed
• Conditions: Glomerulonephritis , IGA
• Intervention / Treatment: Biological: infusion of ADR-001 (Mesenchymal stem cell)

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Kasugai, Aichi, Japan, 486-8510
      • Kasugai Municipal Hospital
    • Nagoya, Aichi, Japan, 566-8560
      • Nagoya University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. IgA nephropathy diagnosed by renal biopsy.

2. Meet any of the following criteria.

   i. Urinary protein at screening is 0.5 g / gCr or more and eGFR is 60 mL / min / 1.73m^2 or more even if corticosteroids are used for 6 months or more before screening.

   ii. Urine protein of 1.0 g / gCr or more and eGFR of 30 mL / min / 1.73 m^2 or more and less than 60 mL / min / 1.73 m^2 at screening even if corticosteroids are used for 6 months or more before screening.

   iii. Urine protein of 0.5 g / gCr or more and less than 1.0 g / gCr at screening and eGFR of 20 mL / min / 1.73m^2 or more and 60 mL / min / 1.73m^2 or urine protein of 1.0 g / gCr or more at screening And eGFR is 20 mL / min / 1.73m^2 or more and less than 30 mL / min / 1.73m^2.

3. Over 20 years old.
4. Able to provide informed consent.

However, in the first cohort, only 2) -i is applied in the selection criteria 2), and in the second cohort, 2) -i, ii, and iii are applied.

Exclusion Criteria:

1. Nephropathy other than IgA nephropathy, and primary and secondary nephrotic syndrome.
2. Start or increase drug therapy for IgA nephropathy with corticosteroids, immunosuppressants, renin angiotensin system (RAS ) inhibitors, antiplatelet drugs, anticoagulants (warfarin), and n-3 fatty acids (fish oil) within 3 months . Palatal tonsillectomy within 6 months.
3. Treatment with other cells.
4. Participated within 3 months or participating in other clinical trials .
5. Penal transplantation within 3 years or scheduled.
6. Diabetics not well controlled.
7. Malignant neoplasm or history of malignant neoplasm within 5 years, or judged possibility of malignant tumor.
8. Suspected of active infection.
9. Positive for hepatitis B (HB), hepatitis C virus (HCV),human Immunodeficiency virus (HIV), human T-cell leukemia virus 1 (HTLV-1) or syphilis.
10. History of severe hypersensitivity or anaphylactic reaction.
11. Allergic to penicillin antibiotics, aminoglycoside antibiotics or dimethyl sulfoxide (DMSO).
12. Serious complications not related to IgA nephropathy.
13. Bleeding or may bleed, shallow days after surgery or trauma to the central nervous system, history of hypersensitivity to components of heparin preparations, history of heparin-induced thrombocytopenia Previous patient.
14. During pregnancy, lactation, may be pregnant or both men and women who do not agree to give birth control under the guidance of the investigator or investigator during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADR-001; Intravenous infusion of ADR-001 (Mesenchymal stem cell)	Biological: infusion of ADR-001 (Mesenchymal stem cell); Once or twice with two week interval at a dose of 100 x 10 ^ 6 cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Any adverse events are summarized.	until 6 weeks after first administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission (proteinuria, hematuria)	Ratio and time frame to achieve remission are summarized.	at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
Proteinuria	Change from baseline value and ratio to achieve threshold are summarized.	at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
Hematuria	Change from baseline value and ratio to achieve threshold are summarized.	at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
Estimated glomerular filtration rate (eGFR)	Change from baseline value are summarized.	at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration

Collaborators and Investigators

• Sponsor: Nagoya University
• Collaborators: Rohto Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Shoichi Maruyama, MD, PhD, Nagoya University

Publications and helpful links

General Publications

• Tanaka A, Furuhashi K, Fujieda K, Maeda K, Saito S, Mimura T, Saka Y, Naruse T, Ishimoto T, Kosugi T, Kinoshita F, Kuwatsuka Y, Shimizu S, Nakai Y, Maruyama S. Protocol for a Phase 1, Open-Label, Multiple-Center, Dose-Escalation Study to Evaluate the Safety and Tolerability of ADR-001 in the Treatment of Immunoglobulin A Nephropathy. Front Med (Lausanne). 2022 May 27;9:883168. doi: 10.3389/fmed.2022.883168. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulonephritis, IGA
• Other Study ID Numbers: CAMCR013; jRCT2043200002 (Other Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No