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

NCT04988087 | Terminated Phase 2 Results

• 2 other identifiers: CMHV370A122012020-004937-19
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 10

Brief Summary

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).

Conditions

Sjogren Syndrome; Mixed Connective Tissue Disease

Keywords

Sicca Syndrome; Sjogren Syndrome; Connective Tissue Disease, Mixed; MCTD; Sharp Syndrome

Outcome Measures

Primary Outcomes (2)

• SjS Participants: Change From Baseline in Eular Sjögren's Disease Activity Index (ESSDAI) After 24 Weeks of Treatment

  The ESSDAI is an established disease outcome measure for Sjögren's syndrome that classifies disease activity in 3-4 levels according to their severity (i.e., no, low, moderate, high), over each of 12 organ-specific domains. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The score range is 0 - 123, where a higher ESSDAI score indicates more severe symptoms. A negative change score from baseline indicates improvement.

  Baseline, Week 24

• MCTD Participants: Change From Baseline in Physician's Global Assessment Scale (PhGA) After 24 Weeks of Treatment

  The physician's global assessment scale is used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). A negative change score from baseline indicates improvement. Only participants with evaluable records are included.

  Baseline, Week 24

Secondary Outcomes (18)

• SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State

  pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

• SjS and MCTD Participants: Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours (AUC0-6h) of MHV370

  pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

• SjS and MCTD Participants: Time to Reach Maximum Plasma Concentrations (Tmax) of MHV370 at Steady State

  pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

• SjS and MCTD Participants: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale

  Baseline, Weeks 4, 8, 12, 20 and 24

• SjS and MCTD Participants: Change From Baseline in Physician Global Assessment (PhGA)

  Baseline, Weeks 4, 8, 12, 20 and 24

Study Arms (4)

SjS participants: MHV370

EXPERIMENTAL

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

Drug: MHV370

SjS participants: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

MCTD participants: MHV370

EXPERIMENTAL

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

Drug: MHV370

MCTD participants: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

MHV370 DRUG

MHV370 for 24 weeks

MCTD participants: MHV370; SjS participants: MHV370

Placebo DRUG

Placebo for 24 weeks

MCTD participants: Placebo; SjS participants: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Székesfehérvár, Fejér, 8000, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Bialystok, Podlaskie Voivodeship, 15 707, Poland

Location

Novartis Investigative Site

Lublin, 20-954, Poland

Location

Novartis Investigative Site

Warsaw, 02 637, Poland

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Kaohsiung City, 81346, Taiwan

Location

Related Publications (2)

• Raaphorst J, Gullick NJ, Shokraneh F, Brassington R, Min M, Ali SS, Gordon PA. Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies. Cochrane Database Syst Rev. 2025 Aug 11;8(8):CD015855. doi: 10.1002/14651858.CD015855.

  PMID: 40787733 DERIVED

• Raaphorst J, Gullick NJ, Shokraneh F, Brassington R, Min M, Ali SS, Gordon PA. Targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies. Cochrane Database Syst Rev. 2025 Aug 1;8(8):CD015854. doi: 10.1002/14651858.CD015854.

  PMID: 40747756 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Sjogren's Syndrome; Mixed Connective Tissue Disease

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 3, 2021
• Study Start: November 30, 2021
• Primary Completion: February 7, 2023
• Study Completion: March 7, 2023
• Last Updated: October 9, 2024
• Results First Posted: July 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); PL (3); CN (2); HU (2); TW (1); ES (1)