Safety and Efficacy of ONT01 in Lupus

NCT07107659 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2024-0364
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

ONT01 is a drug that is being studied for the treatment of Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE) and is not approved by the FDA. The purpose of this study is to better determine whether ONT01 is safe and tolerated by people with lupus nephritis or SLE. The study also looks at how the administration of ONT01 in combination with widely used treatments given for lupus, including the medication mycophenolate mofetil and others, can improve symptoms of lupus. A total of 61 participants will be enrolled in this study.

Conditions

Lupus Nephritis (LN); Lupus Nephritis - WHO Class III; Lupus Nephritis - WHO Class IV; Lupus Nephritis - World Health Organization (WHO) Class III; Lupus; SLE; Systemic Lupus Erythematosus; Systemic Lupus Erythematosus (Disorder)

Keywords

Lupus Nephritis; Lupus; SLE

Outcome Measures

Primary Outcomes (1)

• Adverse Events, Study Completion versus Withdrawal

  This pilot phase 1 study will establish the highest safe dose of ONT01 and help generate preliminary evidence in support of future, large-scale, multi-site, controlled Phase 2 efficacy clinical trials with ONT01 in lupus, so that it can be developed as a novel, myeloid directed, oral therapeutic for lupus.

  From Enrollment until 18 weeks

Secondary Outcomes (1)

• Effect on SLE and Lupus Nephritis Biomarkers at Day 28

  From baseline until Day 28

Study Arms (1)

This study will treat patients with Lupus Nephritis (LN) or Systemic Lupus Erythematosus (SLE).

EXPERIMENTAL

Lupus Nephritis

Drug: ONT01 is a small molecule CD11b modulator.

Interventions

ONT01 is a small molecule CD11b modulator. DRUG

ONT01 will be administered orally twice daily (in the morning and in the evening at approximately 12 hours apart and approximately the same time each day) and should be taken as whole tablets (not crushed) under fasted conditions (2 hours before and 1 hour after each dose) with 8 oz/240 mL of water.

This study will treat patients with Lupus Nephritis (LN) or Systemic Lupus Erythematosus (SLE).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years old and able to provide informed consent to participate.
• Diagnosis of SLE and have fulfilled the ACR classification criteria for SLE during the course of their disease.
• 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
• 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

You may not qualify if:

• 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.
• Active central nervous system SLE associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol.
• 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).
• 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.
• 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.
• History, or current diagnosis, of active tuberculosis (TB), or untreated latent TB infection (LTBI), determined by a positive QuantiFERON test at the Screening Visit
• 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.
• Immunization with live or live-attenuated vaccines within 1 month before or during the Screening period.
• 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.
• Treatment with Voclosporin or Cyclophosphamide at time of screening.
• 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.
• 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

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• The University of Texas Medical Branch, Galveston: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: August 6, 2025
• Study Start (Estimated): September 4, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)