Multiple Ascending Dose Study of MHS552 in Adults Participants With Systemic Lupus Erythematosus (SLE)

NCT ID: NCT05203419

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-15
• Study Completion Date: 2023-06-04

Brief Summary

The purpose of this two-part multiple ascending dose study is to evaluate the safety and tolerability of multiple doses of MHS552 in adults with mild to moderately active Systemic Lupus Erythematosus (SLE). Participants will be treated for 4 or 12 weeks followed by an 8-week follow-up period.

Detailed Description

This was a Phase 1b, randomized, placebo-controlled, participant- and investigator- blinded, two-part non-confirmatory multiple ascending dose (MAD) study in adult patients aged 18-65 (inclusive) with active SLE disease (mild-moderate).This MAD study was planned to be conducted in two parts, Part A and Part B sequentially, but the study was terminated before Part B was initiated.

In Part A, after a screening period of up to 6 weeks, participants were randomized (in a 3:1 ratio) to MHS552 or placebo administered subcutaneously (s.c.) weekly for four weeks of treatment. Part A was planned to consist of up to 3 cohorts (low, medium, high dose). Due to termination of the trial, Part A consisted of 2 cohorts (low and medium doses). Participants were followed-up during 8 weeks post last dose. The total duration of study participation of Part A was approximately 120 Days.

In Part B (not started due to termination of the trial), it was planned that after a screening period of up to 28 days, approximately 12 participants to be randomized (in a 2:1 ratio) to MHS552 or placebo administered s.c. weekly for 12 weeks of treatment (dose to be confirmed).

Conditions

Lupus Erythematosus, Systemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: Cohort 1 - MHS552 low dose

Participants will receive MHS552 low dose once weekly subcutaneously for 4 weeks

Group Type: EXPERIMENTAL

MHS552

Intervention Type: DRUG

MHS552 will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Part A: Cohort 1, 2, 3 - Placebo

Participants will receive placebo once weekly subcutaneously for 4 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Part A: Cohort 2 - MHS552 medium dose

Participants will receive MHS552 medium dose once weekly subcutaneously for 4 weeks

Group Type: EXPERIMENTAL

MHS552

Intervention Type: DRUG

MHS552 will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Part A: Cohort 3 - MHS552 high dose

Participants will receive MHS552 high dose once weekly subcutaneously for 4 weeks

Group Type: EXPERIMENTAL

MHS552

Intervention Type: DRUG

MHS552 will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Part B: MHS552

Participants will receive MHS552 (dose to be determined) once weekly subcutaneously for 12 weeks

Group Type: EXPERIMENTAL

MHS552

Intervention Type: DRUG

MHS552 will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Part B: Placebo

Participants will receive placebo once weekly subcutaneously for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Interventions

MHS552

MHS552 will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Intervention Type: DRUG

Placebo

Placebo will be administered once weekly as subcutaneous injection for 4 weeks (Part A) or 12 weeks (Part B)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Fulfills the 2019 EULAR/American College of Rheumatology (ACR) classification criteria for SLE at least 3 months prior to and at screening.
• Patients with mild or moderately active SLE (SLEDAI-2K between 3 and 10, inclusive) at screening. Patients with cutaneous lupus are eligible as long as they satisfy the criteria for systemic lupus.
• Patients must be on stable dose(s) of at least one of the following medications, unless the medication has been discontinued due to intolerance, inadequate response, or patient/physician decision:

• steroid at a dose ≥ 5mg but <30 mg of prednisone (or equivalent) per day,
• antimalarial (hydroxychloroquine/chloroquine/quinacrine) or thalidomide,
• disease modifying anti-rheumatic drugs (DMARDs):
• methotrexate (MTX),
• azathioprine (AZA),
• mizoribine,
• mycophenolate derivates. Steroid dose must be stable for at least 4 weeks prior to the first dosing. The dose of the other medications above must be stable for at least 12 weeks prior to the first dosing. If the patient is not on any medications listed above, they must have been off these medications for at least 12 weeks prior to dosing.

• Systemic autoimmune disease other than lupus, which would interfere with participation in the study according to the Investigator's judgement. Treated, stable Hashimoto's thyroiditis is not exclusionary.
• Any of the following abnormal laboratory values at Screening or pre-dose Day 1 assessment:

Hemoglobin levels below 8.0 g/dL at screening Eosinophil count >700 mm3 or >2 X Upper Limit of Normal (ULN), whichever is lower.

• History of capillary leak syndrome (CLS).

Exclusion Criteria

• History of hypersensitivity to drugs of similar biological class, IL-2 protein analogues, or hypersensitivity to any components of the study drug, or history of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g. human monoclonal antibody.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Berlin, , Germany

Countries

Germany

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18163

Study Results

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2084

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

2021-003520-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMHS552D12101

Identifier Type: -

Identifier Source: org_study_id