Clinical trial NCT04988087: A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)
Official title: A Multi-center, Randomized, Participant- and Investigator- Blinded, Placebo-controlled, Parallel Group Basket Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjögren's Syndrome or Mixed Connective Tissue Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sjogren Syndrome
Mixed Connective Tissue Disease
Keywords: Sicca Syndrome
Sjogren Syndrome
Connective Tissue Disease, Mixed
MCTD
Sharp Syndrome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-08-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: SjS Participants: Change From Baseline in Eular Sjögren's Disease Activity Index (ESSDAI) After 24 Weeks of Treatment
timeFrame: Baseline, Week 24
measure: MCTD Participants: Change From Baseline in Physician's Global Assessment Scale (PhGA) After 24 Weeks of Treatment
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State
timeFrame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4
measure: SjS and MCTD Participants: Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours (AUC0-6h) of MHV370
timeFrame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4
measure: SjS and MCTD Participants: Time to Reach Maximum Plasma Concentrations (Tmax) of MHV370 at Steady State
timeFrame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4
measure: SjS and MCTD Participants: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
timeFrame: Baseline, Weeks 4, 8, 12, 20 and 24
measure: SjS and MCTD Participants: Change From Baseline in Physician Global Assessment (PhGA)
timeFrame: Baseline, Weeks 4, 8, 12, 20 and 24
measure: SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
timeFrame: Baseline, Weeks 4, 8, 12, 20 and 24
measure: SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI)
timeFrame: baseline, weeks 4, 8, 12, 20 and 24
measure: SjS Participants: Change From Baseline to the Salivary Flow Rate
timeFrame: Baseline, Weeks 4, 12 and 24
measure: SjS Participants: Change From Baseline to the Schirmer's Test
timeFrame: Baseline, Week 4, 12 and 24
measure: SjS Participants: Sjögren's Tool for Assessing Response (STAR) Response Over Time up to Week 24
timeFrame: Baseline, Week 4, 12 and 24
measure: MCTD: Change From Baseline in Articular and Pulmonary Domains of the Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
timeFrame: Baseline, Weeks 4, 8, 12 and 24
measure: MCTD Participants: Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline, Week 12
measure: MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Second (FEV1) of a Forced Breath
timeFrame: Baseline, Week 12
measure: MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Two Seconds (FEV2) of a Forced Breath
timeFrame: Baseline, Week 12
measure: MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Three Seconds (FEV3) of a Forced Breath
timeFrame: Baseline, Week 12
measure: MCTD Participants: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
timeFrame: Baseline, Week 24
measure: MCTD Participants: Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD)
timeFrame: Baseline, Weeks 4, 8, 12 and 24
measure: MCTD Participants: Change From Baseline in Raynaud's Condition Score (RCS)
timeFrame: Baseline, Weeks 4, 12 and 24
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
state: Podlaskie
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: