MIL116 for people with IgA nephropathy and healthy volunteers

A Phase I/II, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of MIL116 in Healthy Participants and Patients With IgA Nephropathy

This trial will test whether subcutaneous MIL116, an anti‑APRIL antibody, is safe and how it behaves in the body in adults with IgA nephropathy and in healthy volunteers.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Mabworks Biotech Co., Ltd. (industry)
• Drugs / interventions: rituximab, belimumab, eculizumab, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Beijing)
• Trial ID: NCT07375758 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial gives subcutaneous MIL116 or matching placebo to healthy adults and to adults with IgA nephropathy to characterize safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD). Early cohorts enroll healthy volunteers to define dose and safety, followed by patient cohorts to examine biological effects and tolerability in the target population. The study measures drug levels, immune markers related to APRIL and standard safety labs, with placebo control used for comparison. Results will inform dosing and whether larger efficacy trials are warranted.

Who should consider this trial

Good fit: Adults (age ≥18) with biopsy-confirmed IgA nephropathy who meet the study's lab, health and BMI requirements and are willing to follow study procedures are the intended participants.

Not a fit: People with advanced kidney failure, unstable medical conditions, or who do not meet the study's eligibility (laboratory, weight or health) criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, MIL116 could reduce APRIL-driven abnormal IgA production and slow kidney inflammation and disease progression in IgA nephropathy.

How similar studies have performed: Other early clinical programs targeting APRIL/related B‑cell pathways have shown promising signals but remain experimental for IgA nephropathy.

Eligibility criteria

Inclusion Criteria:

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Phase Ia:

1. Able to understand and voluntarily sign the written Informed Consent Form (ICF), willing and able to comply with all study requirements;
2. Healthy participants aged 18 to 55 years (inclusive) at the time of signing the ICF, of either sex;
3. Have a body mass index (BMI) between 19 to 32 kg/m² (inclusive) and a body weight ≥ 50 kg at screening;
4. Assessed to be in good health status based on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests, with no clinically significant abnormalities;
5. Have a total immunoglobulin G (IgG) level \> 10 g/L at screening; and immunoglobulin A (IgA) and immunoglobulin M (IgM) levels within the normal reference ranges.

Phase Ib\&II:

1. Able to understand and voluntarily sign the written ICF, and willing and able to comply with all study requirements;
2. Aged ≥ 18 years at the time of signing the ICF, of either sex, with a BMI ≥ 16 kg/m²;
3. Biopsy-confirmed diagnosis of IgA Nephropathy (IgAN). Participants must have a 24-hour urine protein-to-creatinine ratio (UPCR) ≥ 0.5 g/g or 24-hour urine protein ≥ 0.75 g prior to the first dose;
4. Have been receiving an optimized and stable dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor antagonist (ARB). If currently receiving sodium-glucose cotransporter 2 inhibitors (SGLT2i) and / or endothelin receptor antagonists (ERA), the same administration and dose stability requirements apply for;
5. Have acceptable hematologic, hepatic, coagulation, and renal function as assessed by clinical laboratory tests.

Exclusion Criteria:

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Phase Ia:

1. Nursing, lactating or pregnant, or who have plans to become pregnant during the study
2. History or evidence of any clinically significant disease, disorder, or condition that, in the investigator's judgment, may pose a risk to the participants' safety, interfere with the study assessments, or render the subject unsuitable for participation, including but not limited to respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurologic, cardiovascular, psychiatric, or other systemic diseases;
3. Any confirmed or suspected immunosuppressive or immunodeficiency condition, including human immunodeficiency virus (HIV) infection or asplenia; history of recurrent or severe infections, or long-term use of immunosuppressive agents within 6 months prior to screening;
4. History of chronic infection (e.g., tuberculosis, osteomyelitis) or any infectious disease requiring hospitalization or treatment with antiviral, antibiotic, or antifungal agents within 28 days prior to administration of the study drug;
5. Use of any prescription medications, over-the-counter (OTC) drugs, herbal products, topical products, or dietary supplements within 28 days prior to administration of the study drug or for within 5 half-lives of the drug (whichever is longer);
6. Participation in any clinical study of an investigational drug or medical device, or receipt of any investigational study drug, within 3 months prior to administration of the study drug or within 5 half-lives (whichever is longer);
7. Receipt of any marketed or investigational antibody or biologic therapy (including immunoglobulin products, monoclonal antibodies, or antibody fragments) within 28 days prior to administration of the study drug or within 5 half-lives (whichever is longer);
8. History of drug abuse or substance dependence, or a positive urine drug abuse screening result during the screening period.

Phase Ib\&II:

1. Secondary IgAN or IgA vasculitis (Henoch-Schönlein purpura), as diagnosed by the investigator;
2. Presence of chronic kidney disease of causes other than IgAN;
3. Other significant pathological abnormalities identified on kidney biopsy;
4. Kidney biopsy demonstrating tubular-interstitial fibrosis \> 50% or glomerular crescents involving \> 25% of glomeruli. Note: The most recent kidney biopsy will be prioritized for eligibility assessment;
5. Clinical suspicion of rapidly progressive glomerulonephritis based on an estimated glomerular filtration rate (eGFR) decline ≥ 50% within 3 months prior to the screening visit;
6. Nephrotic syndrome, defined as 24-hour urine protein \> 3.5 g accompanied by hypoalbuminemia (serum albumin \< 30 g/L). Subjects with isolated nephrotic-range proteinuria (\> 3.5 g/d) are excluded;
7. Receipt of rituximab or any B-cell depleting agent within 6 months prior to screening. Participants with CD4+ T-cell count \< 200 cells/μL are excluded;
8. Total IgG level \< 6 g/L at screening; uncontrolled type 2 diabetes mellitus, defined as glycated hemoglobin (HbA1c) \> 8%; or diagnosis of type 1 diabetes mellitus;
9. History of prior treatment with any APRIL-targeted medication;
10. Receipt of biologic agents, such as belimumab or eculizumab, within 3 months prior to the first dose of the study drug;
11. Receipt of cyclophosphamide within 3 months prior to the first dose; use of other immunosuppressive agents within 28 days prior to the first dose, including but not limited to azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, methotrexate, or tripterygium wilfordii; systemic corticosteroids used at an average daily dose equivalent to ≥40 mg prednisone for more than 14 days within 28 days prior to the screening visit, or use of oral delayed-release budesonide capsules within 1 year prior to the screening visit.

Where this trial is running

Beijing

• Peking University First Hospital — Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Hong Zhang, Doctor

Conditions: Immunoglobulin A Nephropathy, Anti-APRIL monoclonal antibody, MIL116, IgAN, CLYM116