ONT01 for Lupus Nephritis and Systemic Lupus Erythematosus

Safety and Efficacy of ONTO1 in Lupus

We will test whether ONT01 is safe and helps adults with lupus nephritis or active SLE when added to standard medicines like mycophenolate.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 61 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital for Special Surgery, New York (other)
• Drugs / interventions: Cyclophosphamide
• Locations: 1 site (New York, New York)
• Trial ID: NCT07107659 on ClinicalTrials.gov

What this trial studies

ONT01 is an oral small-molecule CD11b modulator being given to adults with active SLE or biopsy-confirmed class III–V lupus nephritis to measure safety, tolerability, and early signs of clinical benefit. This early phase 1 interventional study plans to enroll about 61 participants at the Hospital for Special Surgery and will give ONT01 in combination with commonly used lupus treatments such as mycophenolate mofetil. Eligible participants include adults with active non-renal SLE (SLEDAI ≥6) who have failed at least one DMARD, or those with active nephritis with recent biopsy and persistent proteinuria despite induction/maintenance therapy. The study will monitor labs, disease activity scores, and urine protein measurements to identify adverse effects and any improvements in lupus activity or kidney function.

Who should consider this trial

Good fit: Adults (≥18) with ACR-classified SLE who have active non-renal disease (SLEDAI ≥6) after failing at least one DMARD, or adults with biopsy-confirmed class III–V lupus nephritis and persistent proteinuria (urine protein/creatinine ≥1 g/g) despite mycophenolate and standard care are ideal candidates.

Not a fit: People with mild or inactive SLE, those under 18, pregnant individuals, or patients whose kidney disease is stable or who have contraindications to study medications are unlikely to receive benefit from this study.

Why it matters

Potential benefit: If successful, ONT01 could offer a new targeted treatment option to reduce kidney inflammation and overall SLE activity with an acceptable safety profile.

How similar studies have performed: Targeting CD11b is a relatively novel approach with mostly preclinical and very limited early-phase human data, so clinical benefit in lupus has not yet been established.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years old and able to provide informed consent to participate.
2. Diagnosis of SLE and have fulfilled the ACR classification criteria for SLE during the course of their disease.
3. Active non-renal SLE, with one active non-renal clinical manifestation, who have failed at least 1 disease modifying anti-rheumatic drug (DMARD) therapy (not including hydroxychloroquine and corticosteroids)

   * Active non-renal SLE is defined as having a SLEDAI of 6 or greater (with at least 1 non-renal clinical domain) OR Active nephritis defined as having a no or partial response after initial induction and maintenance therapy with mycophenolate mofetil (and other standard of care therapies) for 3 months or more for class III, IV, IV, V (or combination) nephritis.
   * Active LN is defined as follows: a. kidney biopsy showing Class III, IV, V, III+V, or IV+V, within 1 year from screening, AND b. 24-hour urine protein/creatinine ratio \>=1g/g at screening, AND c. absence of partial renal response (PRR)
   * Partial renal response (PRR) is defined as a. 24-hour UPCR improved by \>=25% after 3 months from the start of induction standard of care (SOC) therapy (baseline), or \>= 50% after 6 months from the induction therapy (UPCR), AND b. 24-hour UPCR\<2g/g if baseline was \< 3g/g, OR \< 3g/g if baseline at induction was \>= 3g/g. AND d. EGFR\>=60 ml/min/1.73 M2 or no less than 80% of Baseline eGFR (at induction) AND e. No intercurrent rescue therapy, death, or early SOC treatment discontinuation or study withdrawal No response (NR) is defined as a. no achievement of at least a partial renal response, OR b. use of intercurrent rescue therapy, OR c. death
4. Female patients who are women of childbearing potential must agree to use a highly effective form of contraception during the study and for at least 120 days after last exposure to study drug. Male patients with female partners of childbearing potential must use effective barrier contraception (i.e., condoms) during the study and for at least 120 days after last exposure to study drug. Also, patients may not proceed with sperm or egg donation during the study and for at least 120 days after the last exposure to study drug

Exclusion Criteria:

1. Any condition, including any uncontrolled disease (eg, asthma, interstitial lung disease, pulmonary arterial hypertension, morbid obesity), that in the Sponsor-Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation.
2. Active central nervous system SLE associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol.
3. Comorbidities requiring systemic corticosteroid (CS) therapy, such as asthma or inflammatory bowel disease. Systemic is defined as oral, rectal or any injectable route of administration (thus stable dosing by other routes is allowed, including inhaled, topical, ophthalmic, otic, and intranasal).
4. 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 of or during the Screening Visit, or completion of oral anti-infectives within 2 weeks before or during the Screening Visit.
5. History of positive human immunodeficiency virus (HIV), hepatitis C antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+), and/or hepatitis B core IgG and/or IgM antibody (+) at the Screening Visit.
6. History, or current diagnosis, of active tuberculosis (TB), or untreated latent TB infection (LTBI), determined by a positive QuantiFERON test at the Screening Visit
7. History of malignancy (hematologic or solid tumor) within 10 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 adequately treated carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.
8. Immunization with live or live-attenuated vaccines within 1 month before or during the Screening period.
9. Initiation of, or change in, dosing of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker within 2 weeks before the Screening Visit or during the Screening period.
10. Treatment with Voclosporin or Cyclophosphamide at time of screening.
11. Treatment with other investigational agents within the last 3 months or 5 half-lives, or as per washout requirement from the previous protocol, whichever is longest, prior to the Screening Visit.
12. Clinically significant abnormalities in laboratory tests, unless attributable to active SLE at the Screening Visit

    * Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level \> 2.5 × upper limit of normal (ULN), or
    * Total bilirubin \> 1.5 × ULN, or
    * Hemoglobin \< 5.0 mmol/L \[9 g/dL\], or
    * White blood cells \< 2.5 × 109/L, or
    * Absolute neutrophil count \< 1500 /mm3, or
    * Platelets \< 75 × 109/L
13. Clinically significant chest imaging (e.g. X-ray, computed tomography or magnetic resonance imaging \[MRI\]) abnormalities per Sponsor-Investigator opinion (e.g. interstitial lung disease) or evidence of active TB on chest X-ray. Chest imaging study must have been performed in 3 months prior to the Screening Visit or during the Screening period.
14. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
15. Patients are unable or unwilling to adhere to the contraception requirements outlined in inclusion criteria 4.

Where this trial is running

New York, New York

• Hospital for Special Surgery — New York, New York, United States (RECRUITING)

Conditions: Lupus Nephritis, Lupus Nephritis - WHO Class III, Lupus Nephritis - WHO Class IV, Lupus Nephritis - World Health Organization Class III, Lupus, SLE, Systemic Lupus Erythematosus