A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)

Novartis

Status and phase: Terminated; Phase 2

Conditions: Sjogren Syndrome; Mixed Connective Tissue Disease

Treatments: Drug: Placebo; Drug: MHV370

Study type: Interventional

Funder types: Industry

Identifiers

NCT04988087

2020-004937-19 (EudraCT Number)

CMHV370A12201

Details and patient eligibility

About

This study was a basket trial designed to establish safety, tolerability and efficacy of MHV370 in Sjögren's Syndrome (SjS) and Mixed Connective Tissue Disease (MCTD).

Full description

This was a randomized, participant and investigator blinded, placebo-controlled, multi center parallel group basket study to evaluate the safety, tolerability and efficacy of MHV370 in participants with Sjögren's Syndrome (SjS) or with Mixed Connective Tissue Disease (MCTD). Participants first underwent a screening period of up to 6 weeks, followed by a treatment duration of 24 weeks and a follow-up period of 4 weeks. Total study duration for each participant was up to 34 weeks. Participants with SjS were randomized in a 1:1 ratio to MHV370 or placebo and participants with MCTD were randomized in a 1:1 ratio to MHV370 or placebo.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

SjS and MCTD:

• Fully vaccinated with any locally approved COVID-19 vaccination including booster vaccinations if required by local guidelines

SjS:

• Unstimulated whole salivary flow rate of > 0 mL/min at screening
• Classification of Sjögren's Syndrome according to the 2016 ACR/EULAR criteria at screening
• Screening ESSDAI (based on weighted score) ≥ 5 from 8 defined domains (biologic, hematologic, articular, cutaneous, glandular, lymphadenopathy, renal, constitutional).

MCTD:

• Diagnosis of MCTD based on criteria like a) Raynaud's phenomenon b) At least two of the four following signs: i) synovitis, ii) myositis, iii) swollen fingers and vi) interstitial lung disease
• Patients with overlap syndromes, i.e. patients meeting diagnostic criteria for systemic autoimmune disease other than MCTD may be included unless they have major organ involvement as judged by the investigator

Exclusion criteria

SjS and MCTD:

• Prior use of B-cell depleting therapy within 6 months of baseline. For participants who received B-cell depleting therapy within 6 -12 months of baseline visit, B-cell count should be within normal range
• Prior treatment with any of the following within 3 months of baseline: CTLA4-Fc Ig (abatacept), Anti-TNF mAb, Intravenous Ig, Plasmapheresis, i.v. or oral cyclophosphamide, i.v. or oral cyclosporine A
• Screening CBC laboratory values as follows: Hemoglobin levels < 8 g/dL (< 5 mmol/L), Total leukocyte count < 2,000/µL (2 x 109/L), Platelets < 50,000/µL (50 x 109/L), Neutrophil count < 1,000/µL (1 x 109/L)
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they use a highly effective method of contraception

SjS:

• Sjögren's Syndrome overlap syndromes where another autoimmune disease constitutes the primary illness
• Required regular use of medications known to cause, as a major side effect, dry mouth / eyes

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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30 participants in 4 patient groups, including a placebo group

SjS participants: MHV370

Experimental group

Description:

SjS participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.

Treatment:

Drug: MHV370

SjS participants: Placebo

Placebo Comparator group

Description:

SjS participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.

Treatment:

Drug: Placebo

MCTD participants: MHV370

Experimental group

Description:

MCTD participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.

Treatment:

Drug: MHV370

MCTD participants: Placebo

Placebo Comparator group

Description:

MCTD participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.

Treatment:

Drug: Placebo