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

Primary Purpose

Lupus Erythematosus, Systemic

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

MHS552

Placebo

About this trial

This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Systemic Lupus Erythematosus, Lupus, autoimmune disease, inflammatory disease, inflammation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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.
Patients with central nervous system (CNS) lupus, active Lupus Nephritis, any type of lupus flare requiring pulse steroid or immunosuppressive therapy with cyclophosphamide, rituximab, calcineurin inhibitors, or others except those permitted in the inclusion criteria.
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).

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A: Cohort 1 - MHS552 low dose

Part A: Cohort 1, 2, 3 - Placebo

Part A: Cohort 2 - MHS552 medium dose

Part A: Cohort 3 - MHS552 high dose

Part B: MHS552

Part B: Placebo

Arm Description

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

Participants will receive placebo once weekly subcutaneously for 4 weeks

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

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

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

Participants will receive placebo once weekly subcutaneously for 12 weeks

Outcomes

Primary Outcome Measures

Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)

Numbers of participants with AEs and SAEs, and other safety data such as vital signs, electrocardiograms (ECG) and laboratory results

Secondary Outcome Measures

Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552

Characterize the AUCtau profile following multiple doses of MHS552

Maximum Observed Blood Concentrations (Cmax) for MHS552

Characterize the Cmax profile following multiple doses of MHS552

Time to Reach Maximum Blood Concentrations (Tmax) of MHS552

Characterize the Tmax profile profile following multiple doses of MHS552

Full Information

NCT ID

NCT05203419

First Posted

January 10, 2022

Last Updated

September 26, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05203419

Brief Title

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

Official Title

A Two-part, Randomized, Investigator- and Participant- Blinded, Placebo-controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MHS552 in Adult Participants With Systemic Lupus Erythematosus (SLE)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Sponsor Decision

Study Start Date

March 15, 2022 (Actual)

Primary Completion Date

June 4, 2023 (Actual)

Study Completion Date

June 4, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Erythematosus, Systemic

Keywords

Systemic Lupus Erythematosus, Lupus, autoimmune disease, inflammatory disease, inflammation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: Cohort 1 - MHS552 low dose

Arm Type

Experimental

Arm Description

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

Arm Title

Part A: Cohort 1, 2, 3 - Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive placebo once weekly subcutaneously for 4 weeks

Arm Title

Part A: Cohort 2 - MHS552 medium dose

Arm Type

Experimental

Arm Description

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

Arm Title

Part A: Cohort 3 - MHS552 high dose

Arm Type

Experimental

Arm Description

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

Arm Title

Part B: MHS552

Arm Type

Experimental

Arm Description

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

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive placebo once weekly subcutaneously for 12 weeks

Intervention Type

Drug

Intervention Name(s)

MHS552

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)

Description

Numbers of participants with AEs and SAEs, and other safety data such as vital signs, electrocardiograms (ECG) and laboratory results

Time Frame

Part A: up to 12 weeks; Part B: up to 20 weeks

Secondary Outcome Measure Information:

Title

Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552

Description

Characterize the AUCtau profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

Title

Maximum Observed Blood Concentrations (Cmax) for MHS552

Description

Characterize the Cmax profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

Title

Time to Reach Maximum Blood Concentrations (Tmax) of MHS552

Description

Characterize the Tmax profile profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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. 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. Patients with central nervous system (CNS) lupus, active Lupus Nephritis, any type of lupus flare requiring pulse steroid or immunosuppressive therapy with cyclophosphamide, rituximab, calcineurin inhibitors, or others except those permitted in the inclusion criteria. 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). Other protocol-defined inclusion/exclusion criteria may apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

10117

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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