Clinical trial NCT06335979: An Ascending Dose Study of PIT565 in Participants With Systemic Lupus Erythematosus (SLE).
Official title: A Phase Ib, Open-label, Ascending Dose Study With Step-up Doses to Assess Safety, Tolerability, and Pharmacokinetics of PIT565 in Participants With Systemic Lupus Erythematosus (SLE).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus, SLE
Keywords: Systemic lupus erythematosus, SLE, ascending dose, B cells
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 have 3 sentinel participants and, depending on safety as well as observed biological activity, may have up to 3 additional optional participants (up to 6 participants per cohort). 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 optionally be enriched with 6 additional participants (up to a total of 12 participants).

Eligibility criteria: 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, 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 immune-suppressive 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/exclusion criteria may apply.

Primary outcomes:
measure: Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
timeFrame: From Study Day 1 until Study Day 180
Secondary outcomes:
measure: Maximum Observed Blood Concentrations (Cmax)
timeFrame: From pre-dose Day 1 until Day 29
measure: Time to Reach Maximum Blood Concentrations (Tmax)
timeFrame: From pre-dose Day 1 until Day 29
measure: Presence/absence of Anti-drug Antibodies
timeFrame: From pre-dose Day 1 until Day 180
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: St Gallen
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: