- ICH GCP
- US Clinical Trials Registry
- 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)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510000
- Novartis Investigative Site
-
-
Jilin
-
Chang Chun, Jilin, China, 130021
- Novartis Investigative Site
-
-
-
-
-
Berlin, Germany, 10117
- Novartis Investigative Site
-
-
-
-
-
Debrecen, Hungary, 4032
- Novartis Investigative Site
-
-
Fejer
-
Szekesfehervar, Fejer, Hungary, 8000
- Novartis Investigative Site
-
-
-
-
-
Lublin, Poland, 20-954
- Novartis Investigative Site
-
Warszawa, Poland, 02 637
- Novartis Investigative Site
-
-
Podlaskie
-
Bialystok, Podlaskie, Poland, 15 707
- Novartis Investigative Site
-
-
-
-
-
Madrid, Spain, 28041
- Novartis Investigative Site
-
-
-
-
-
Kaohsiung, Taiwan, 81346
- Novartis Investigative Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SjS participants: MHV370
SjS participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks.
Double-blind supply will be used.
|
MHV370 for 24 weeks
|
Placebo Comparator: SjS participants: Placebo
SjS participants randomized in the placebo arm will be treated with placebo for 24 weeks.
Double-blind supply will be used.
|
Placebo for 24 weeks
|
Experimental: MCTD participants: MHV370
MCTD participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks.
Double-blind supply will be used.
|
MHV370 for 24 weeks
|
Placebo Comparator: MCTD participants: Placebo
MCTD participants randomized in the placebo arm will be treated with placebo for 24 weeks.
Double-blind supply will be used.
|
Placebo for 24 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SjS participants: Change from baseline in Eular Sjögren's Disease Activity Index (ESSDAI) after 24 weeks of treatment
Time Frame: baseline, week 24
|
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: biologic (1), hematologic (2), articular (2), glandular (2), cutaneous (3), constitutional (3), lymphadenopathy (4), renal (5), pulmonary (5), PNS (5), CNS (5) and muscular (6).
The maximum possible score is 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
Time Frame: baseline, week 24
|
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.
|
baseline, week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SjS and MCTD participants: Maximum Observed Blood Concentrations (Cmax) of MHV370 at steady state
Time Frame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
The maximum (peak) observed blood drug concentration after single dose administration (ng / mL).
Pharmacokinetic (PK) parameters will be calculated based on MHV370 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1 ng/mL.
Cmax will be determined using non-compartmental methods.
|
pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
SjS and MCTD participants: Area under the blood concentration-time curve from time zero to time of last measurable concentration (AUClast) of MHV370 at steady state
Time Frame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
The AUC from time zero to the last measurable concentration sampling time (tlast) (ng x h / mL).
Pharmacokinetic (PK) parameters will be calculated based on MHV370 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1 ng / mL.
AUClast will be determined using non-compartmental methods.
|
pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
SjS and MCTD participants: Time to Reach Maximum Blood Concentrations (Tmax) of MHV370 at steady state
Time Frame: pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
The time to reach maximum (peak) blood drug concentration after single dose administration (h).
Pharmacokinetic (PK) parameters will be calculated based on MHV370 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1 ng/mL.
Tmax will be determined using non-compartmental methods.
|
pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 and predose and 4 hours after dosing at weeks 12 and 24
|
SjS and MCTD participants: Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale
Time Frame: baseline, weeks 4, 8, 12, 20 and 24
|
The FACIT-F v4 is a short, 13-item patient-reported measure, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week.
The level of fatigue is measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).
To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52, where a higher FACIT-F score indicates more severe symptoms.
A negative change score from baseline indicates improvement.
|
baseline, weeks 4, 8, 12, 20 and 24
|
SjS and MCTD participants: Change from baseline in Physician Global Assessment (PhGA)
Time Frame: SjS participants: baseline, weeks 4, 8, 12, 20 and 24. MCTD participants: baseline, weeks 4, 8, 12, and 20.
|
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.
|
SjS participants: baseline, weeks 4, 8, 12, 20 and 24. MCTD participants: baseline, weeks 4, 8, 12, and 20.
|
SjS participants: Change from baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
Time Frame: baseline, weeks 4, 8, 12 and 20
|
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: biologic (1), hematologic (2), articular (2), glandular (2), cutaneous (3), constitutional (3), lymphadenopathy (4), renal (5), pulmonary (5), PNS (5), CNS (5) and muscular (6).
The maximum possible score is 123, where a higher ESSDAI score indicates more severe symptoms.
A negative change score from baseline indicates improvement.
|
baseline, weeks 4, 8, 12 and 20
|
SjS participants: Change from baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI)
Time Frame: baseline, weeks 4, 8, 12, 20 and 24
|
The ESSPRI is an established disease outcome measure for Sjögren's syndrome.
The ESSPRI is a patient-reported, subjective symptom index which consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular).
The participant can assess severity of symptoms they experience on a single numerical scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable) for each of the three domains.
The overall ESSPRI score is calculated as the mean of the three individual domains where all domains carry the same weight.
Minimum score can be 0 and maximum score can be 10, where a higher ESSPRI score indicates more severe symptoms.
A negative change score from baseline indicates improvement.
|
baseline, weeks 4, 8, 12, 20 and 24
|
SjS participants: Change from baseline to the salivary flow rate
Time Frame: baseline, weeks 4,12 and 24
|
Unstimulated whole salivary fluid secretions are collected over 5 minutes from participants.
The start time and end time of saliva collection will be recorded to calculate the salivary flow rate per minute.
|
baseline, weeks 4,12 and 24
|
SjS participants: Change from baseline to the Schirmer's test
Time Frame: baseline, weeks 4, 12 and 24
|
Schirmer's test is used to determine whether the eye produces enough tears to keep it moist especially for those who suffer from dry eye syndrome.
A strip is placed in the lower eyelid for 5 minutes to assess tear production.
After 5 minutes, the filter paper is removed and the distance between the leading edge of wetness and the initial fold is measured, using a millimeter ruler.
Tear deficiency is defined as <5 mm wetting of the paper after 5 minutes.
|
baseline, weeks 4, 12 and 24
|
SjS participants: Sjögren's Tool for Assessing Response (STAR) response over time up to week 24
Time Frame: baseline, weeks 4, 12 and24
|
STAR is a composite responder index, including in a single tool all main disease features, and designed for use as a key efficacy endpoint in SjS randomized clinical trials
|
baseline, weeks 4, 12 and24
|
MCTD: Change from baseline in articular and pulmonary domains of the Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
Time Frame: baseline, weeks 4, 8, 12 and 24
|
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.
Participants with Mixed Connective Tissue Disease (MCTD) will complete the articular (from 0 "no activity" to 3 "high activity") and pulmonary (from 0 "no activity to 3 "high activity") domains of the ESSDAI only.
For MCTD participants, the maximum possible score is 21, where a higher score indicates more severe symptoms.
A negative change score from baseline indicates improvement.
|
baseline, weeks 4, 8, 12 and 24
|
MCTD participants: Change from baseline in Forced Vital Capacity (FVC)
Time Frame: baseline, weeks 12 and 24
|
FVC is the total amount of air exhaled during the Forced expiratory volume (FEV) test measured through spirometry testing.
FEV measures how much air a person can exhale during a forced breath.
The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath.
A positive change from baseline is considered a favorable outcome.
(FEV3) of the forced breath.
FVC is the total amount of air exhaled during the FEV test.
|
baseline, weeks 12 and 24
|
MCTD participants: Change from baseline in Forced expiratory volume during the first second (FEV1) of a forced breath
Time Frame: baseline, weeks 12 and 24
|
FEV test measures how much air a person can exhale during a forced breath.
The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath.
The test is measured through spirometry testing.
A positive change from baseline is considered a favorable outcome.
|
baseline, weeks 12 and 24
|
MCTD participants: Change from baseline in Forced expiratory volume during the first two seconds (FEV2) of a forced breath
Time Frame: baseline, weeks 12 and 24
|
FEV test measures how much air a person can exhale during a forced breath.
The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath.
The test is measured through spirometry testing.
A positive change from baseline is considered a favorable outcome.
|
baseline, weeks 12 and 24
|
MCTD participants: Change from baseline in Forced expiratory volume during the first three seconds (FEV3) of a forced breath
Time Frame: baseline, weeks 12 and 24
|
FEV test measures how much air a person can exhale during a forced breath.
The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath.
The test is measured through spirometry testing.
A positive change from baseline is considered a favorable outcome.
|
baseline, weeks 12 and 24
|
MCTD participants: Change from baseline in the diffusing capacity of the lungs for carbon monoxide (DLCO)
Time Frame: baseline, weeks 12 and 24
|
DLCO is a measurement to assess the ability of the lungs to transfer gas from inspired air to the bloodstream.
Inhaled carbon monoxide (CO) is used for this test due to its high affinity for hemoglobin.
During a ten-second breath-hold, DLCO measures uptake of CO per time per CO pressure (cc of CO/sec/mm of Hg).
A positive change from baseline is considered a favorable outcome.
|
baseline, weeks 12 and 24
|
MCTD participants: Change from baseline in King's Brief Interstitial Lung Disease (K-BILD)
Time Frame: baseline, weeks 4, 8, 12 and 24
|
The K-BILD questionnaire is a self-administered health-status questionnaire that has been developed in patients with interstitial lung diseases.
It consists of 15 items in three domains: breathlessness and activities, psychological factors, and chest symptoms.
Domain and total scores range from 0 to 100, with higher scores representing better health status.
|
baseline, weeks 4, 8, 12 and 24
|
MCTD participants: Change from baseline in Raynaud's Condition Score (RCS)
Time Frame: baseline, weeks 4, 12 and 24
|
The RCS is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon and impact of Raynaud's alone on use of hands every day.
An 11-point Likert scale is used to rate the difficulty caused by the condition with 0 = no difficulty and 10 = extreme difficulty.
Participants are asked to select the number that best describes their difficulty, with higher score indicating worse condition.
|
baseline, weeks 4, 12 and 24
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Eye Diseases
- Disease
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Arthritis
- Stomatognathic Diseases
- Mouth Diseases
- Lacrimal Apparatus Diseases
- Arthritis, Rheumatoid
- Xerostomia
- Salivary Gland Diseases
- Dry Eye Syndromes
- Syndrome
- Connective Tissue Diseases
- Sjogren's Syndrome
- Mixed Connective Tissue Disease
Other Study ID Numbers
- CMHV370A12201
- 2020-004937-19 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sjogren Syndrome
-
Pontificia Universidad Catolica de ChileFormulario MAgistral Farmacias AhumadaCompletedXerostomia | Primary Sjogren | Secondary SjogrenChile
-
Federal University of São PauloAllerganCompletedEvaporative Dry Eye Disease | Primary Sjogren Syndrome | Secondary Sjogren Syndrome | Aqueous Deficient Dry Eye DiseaseBrazil
-
Novartis PharmaceuticalsRecruitingSjogren SyndromeUnited States, Brazil, Mexico, Portugal, Turkey, Belgium, Spain, Chile, Germany, Guatemala, Korea, Republic of, Czechia, France, China, Austria, Poland, Singapore, Lithuania
-
University of NebraskaCompletedSjogren-Larsson Syndrome (SLS)United States
-
University of Roma La SapienzaUnknown
-
Novartis PharmaceuticalsRecruitingSjogren SyndromeUnited States, Spain, Hungary, Germany, Brazil, Israel, Canada, Chile, Colombia, Argentina, Greece, United Kingdom, Australia, Bulgaria, Japan, Mexico, South Africa, China, Lebanon, Taiwan, Italy, France, Romania, India, Poland, Slovakia, S...
-
Novartis PharmaceuticalsActive, not recruiting
-
Novartis PharmaceuticalsCompletedPrimary Sjogren SyndromeUnited States, Belgium, Italy, Austria, Israel, France, Germany, Hungary, Netherlands, United Kingdom, Japan, Portugal, Argentina, Spain, Taiwan, Russian Federation, Romania, Chile, Poland
-
Federal University of São PauloCompletedXEROSTOMIA | KERATOCONJUNCTIVITIS SICCA | SICCA SYNDROME | PRIMARY SJOGREN SYNDROMEBrazil
-
Meir Medical CenterUnknownPrimary Sjogren Syndrome With Multisystem Involvement