Clinical trial NCT04342325: The Clinical Trial of ADR-001 for IgA Nephropathy
Official title: Open-label, Multiple-center, Dose-Escalation Study to Evaluate the Safety and Tolerability of ADR-001 for the Treatment for Immunoglobulin A (IgA) Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glomerulonephritis , IGA
Lead sponsor: Nagoya University
Sponsor class: OTHER
Collaborators: name: Rohto Pharmaceutical Co., Ltd.
First posted: 2020-04-13
Enrollment: 9
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 3 + 3 dose escalation study design
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: until 6 weeks after first administration
Secondary outcomes:
measure: Clinical remission (proteinuria, hematuria)
timeFrame: at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
measure: Proteinuria
timeFrame: at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
measure: Hematuria
timeFrame: at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: at 2, 4, 6, 12, 26, 38 and 52 weeks after first administration
Other outcomes:
Locations:
city: Kasugai
country: Japan
facility: Kasugai Municipal Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
Study officials:
affiliation: Nagoya University
name: Shoichi Maruyama, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.