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.
≥ 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.
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.
Single group
ONT01 is a small molecule CD11b modulator.
DrugONT01 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.
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.
Effect on SLE and Lupus Nephritis Biomarkers at Day 28
Proportion of patients with statistically significant reduction in * suPAR (ng/mL) * Proteinuria (protein to creatinine ratio (mg/g) * C5a (ng/mL) * IL-16 (ng/mL) * Anti-dsDNA antibodies (IU/mL) * Active SLE symptoms (presence or absence of active symptoms as defined by the SLEDAI criteria) Lupus Nephritis secondary outcomes: 25 participants will be enrolled. which will allow us to detect a 1.24-fold difference in a biomarker with 80% power, assuming a 30% standard deviation, with an alpha of 0.01. Active non-renal lupus secondary outcomes: 36 participants will be enrolled, which will allow us to detect a 1.24-fold difference in a biomarker with 80% power, assuming 30% standard deviation, with an alpha of 0.01.
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Hospital for Special Surgery, New York
Lead sponsor
The University of Texas Medical Branch, Galveston
Collaborator
