An Ascending Dose Study of PIT565 in Participants With Systemic Lupus Erythematosus (SLE).

Phase 1

Recruiting

• Conditions: Systemic Lupus Erythematosus, SLE
• Interventions: Drug: PIT565

• Registration Number: NCT06335979
• Lead Sponsor: Novartis Pharmaceuticals

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).

Study Timeline

• Study First Submitted: 2024-03-22
• Study First Submitted QC: 2024-03-22
• Study First Posted: 2024-03-28
• Study Start: 2024-10-08
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-13
• Last Update Posted: 2025-08-17
• Primary Completion: 2027-07-09
• Study Completion: 2027-07-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

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/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	PIT565	Dose level 1
Cohort 2	PIT565	Dose level 2
Cohort 3	PIT565	Dose level 3
Cohort 5	PIT565	Dose level 5
Cohort 4	PIT565	Dose level 4
Cohort 6	PIT565	Dose level 6
Cohort 7	PIT565	Dose level 7
Cohort 8	PIT565	Dose level 8

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇭 St Gallen, Switzerland