Systemic Lupus Erythematosus, SLE
Conditions
Keywords
Systemic lupus erythematosus, SLE, ascending dose, B cells
Brief summary
The purpose of the study is to determine the safety, tolerability, and pharmacokinetics of PIT565 in participants with SLE
Detailed description
This is an open-label, ascending dose, uncontrolled study in participants with SLE systemic lupus erythematosus (SLE). PIT565 will be administered subcutaneously (s.c.) following premedication. Up to 8 cohorts are planned. Every cohort will start with 3 sentinel participants and, depending on safety as well as observed biological activity, may have additional optional participants. The decision to escalate the dose from one cohort to the next will be based both on safety and PD data. After the identification of a dose level that has been declared safe and has induced predefined B cell depletion in 100% of the participants (candidate dose level), the cohort from this candidate dose level can be expanded with up to 12 additional participants (up to a total of 15 participants per cohort).
Interventions
DRUGPIT565
In each cohort, there will be 3 sentinel participants. Additional participants might be added depending on safety and observed biological activity.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SLE according to the 2019 ACR/EULAR criteria * Documentation of SLE autoantibodies * Active SLE disease, as demonstrated by a SLEDAI-2K ≥ 4 at screening * Failure to respond to standard-of-care medicines for the treatment of SLE as detailed in the protocol * Immunization against pneumococcus, meningococcus, influenza, and COVID-19
Exclusion criteria
* Severe SLE-related organ damage dysfunction or life-threatening disease at screening. * Any acute, severe lupus-related flare during screening that needs immediate treatment such as acute CNS lupus (e.g., psychosis, epilepsy) or catastrophic antiphospholipid syndrome. * Presence of severe lupus kidney disease as defined by worsening proteinuria or estimated glomerular filtration rate (eGFR) which in the opinion of the Investigator requires immunosuppressive induction or maintenance treatment at screening. * History or current diagnosis of ECG or cardiac abnormalities indicating a significant risk of safety for participants. * Use of prohibited medication defined in the protocol. * Clinically significant active, opportunistic, chronic or recurrent infection (including, HIV, HBV, HCV) confirmed one month prior to or during screening. * Serious medical illness likely to interfere with participation in this clinical study. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs) | From Study Day 1 until Study Day 180 | Safety assessments of PIT565 including changes in vital signs, electrocardiograms (ECG) and laboratory results from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Blood Concentrations (Cmax) | From pre-dose Day 1 until Day 29 | Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1). |
| Presence/absence of Anti-drug Antibodies | From pre-dose Day 1 until Day 180 | Assess immunogenicity of PIT565 at pre-dose, and over time |
Countries
China, Germany, Hungary, Netherlands, Spain, Switzerland
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed