Back to resultsA Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)
Primary Purpose
Sjogren Syndrome, Mixed Connective Tissue Disease
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MHV370
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sjogren Syndrome focused on measuring Sicca Syndrome, Sjogren Syndrome, Connective Tissue Disease, Mixed, MCTD, Sharp Syndrome
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
SjS participants: MHV370
SjS participants: Placebo
MCTD participants: MHV370
MCTD participants: Placebo
Arm Description
SjS participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
SjS participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
MCTD participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
MCTD participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
Outcomes
Primary Outcome Measures
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: 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.
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.
Secondary Outcome Measures
SjS and MCTD participants: Maximum Observed Blood Concentrations (Cmax) of MHV370 at steady state
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.
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
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.
SjS and MCTD participants: Time to Reach Maximum Blood Concentrations (Tmax) of MHV370 at steady state
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.
SjS and MCTD participants: Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale
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.
SjS and MCTD participants: Change from baseline in Physician Global Assessment (PhGA)
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: Change from baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
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.
SjS participants: Change from baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI)
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.
SjS participants: Change from baseline to the salivary flow rate
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.
SjS participants: Change from baseline to the Schirmer's test
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.
SjS participants: Sjögren's Tool for Assessing Response (STAR) response over time up to week 24
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
MCTD: Change from baseline in articular and pulmonary domains of the Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
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.
MCTD participants: Change from baseline in Forced Vital Capacity (FVC)
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.
MCTD participants: Change from baseline in Forced expiratory volume during the first second (FEV1) of a forced breath
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.
MCTD participants: Change from baseline in Forced expiratory volume during the first two seconds (FEV2) of a forced breath
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.
MCTD participants: Change from baseline in Forced expiratory volume during the first three seconds (FEV3) of a forced breath
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.
MCTD participants: Change from baseline in the diffusing capacity of the lungs for carbon monoxide (DLCO)
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.
MCTD participants: Change from baseline in King's Brief Interstitial Lung Disease (K-BILD)
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.
MCTD participants: Change from baseline in Raynaud's Condition Score (RCS)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04988087
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
February 7, 2023 (Actual)
Study Completion Date
March 7, 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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is 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 is 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sjogren Syndrome, Mixed Connective Tissue Disease
Keywords
Sicca Syndrome, Sjogren Syndrome, Connective Tissue Disease, Mixed, MCTD, Sharp Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SjS participants: MHV370
Arm Type
Experimental
Arm Description
SjS participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
Arm Title
SjS participants: Placebo
Arm Type
Placebo Comparator
Arm Description
SjS participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
Arm Title
MCTD participants: MHV370
Arm Type
Experimental
Arm Description
MCTD participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
Arm Title
MCTD participants: Placebo
Arm Type
Placebo Comparator
Arm Description
MCTD participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
Intervention Type
Drug
Intervention Name(s)
MHV370
Intervention Description
MHV370 for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for 24 weeks
Primary Outcome Measure Information:
Title
SjS participants: Change from baseline in Eular Sjögren's Disease Activity Index (ESSDAI) after 24 weeks of treatment
Description
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.
Time Frame
baseline, week 24
Title
MCTD participants: Change from baseline in physician's global assessment scale (PhGA) after 24 weeks of treatment
Description
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.
Time Frame
baseline, week 24
Secondary Outcome Measure Information:
Title
SjS and MCTD participants: Maximum Observed Blood Concentrations (Cmax) of MHV370 at steady state
Description
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.
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
Title
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
Description
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.
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
Title
SjS and MCTD participants: Time to Reach Maximum Blood Concentrations (Tmax) of MHV370 at steady state
Description
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.
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
Title
SjS and MCTD participants: Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale
Description
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.
Time Frame
baseline, weeks 4, 8, 12, 20 and 24
Title
SjS and MCTD participants: Change from baseline in Physician Global Assessment (PhGA)
Description
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.
Time Frame
SjS participants: baseline, weeks 4, 8, 12, 20 and 24. MCTD participants: baseline, weeks 4, 8, 12, and 20.
Title
SjS participants: Change from baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
Description
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.
Time Frame
baseline, weeks 4, 8, 12 and 20
Title
SjS participants: Change from baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI)
Description
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.
Time Frame
baseline, weeks 4, 8, 12, 20 and 24
Title
SjS participants: Change from baseline to the salivary flow rate
Description
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.
Time Frame
baseline, weeks 4,12 and 24
Title
SjS participants: Change from baseline to the Schirmer's test
Description
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.
Time Frame
baseline, weeks 4, 12 and 24
Title
SjS participants: Sjögren's Tool for Assessing Response (STAR) response over time up to week 24
Description
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
Time Frame
baseline, weeks 4, 12 and24
Title
MCTD: Change from baseline in articular and pulmonary domains of the Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)
Description
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.
Time Frame
baseline, weeks 4, 8, 12 and 24
Title
MCTD participants: Change from baseline in Forced Vital Capacity (FVC)
Description
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.
Time Frame
baseline, weeks 12 and 24
Title
MCTD participants: Change from baseline in Forced expiratory volume during the first second (FEV1) of a forced breath
Description
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.
Time Frame
baseline, weeks 12 and 24
Title
MCTD participants: Change from baseline in Forced expiratory volume during the first two seconds (FEV2) of a forced breath
Description
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.
Time Frame
baseline, weeks 12 and 24
Title
MCTD participants: Change from baseline in Forced expiratory volume during the first three seconds (FEV3) of a forced breath
Description
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.
Time Frame
baseline, weeks 12 and 24
Title
MCTD participants: Change from baseline in the diffusing capacity of the lungs for carbon monoxide (DLCO)
Description
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.
Time Frame
baseline, weeks 12 and 24
Title
MCTD participants: Change from baseline in King's Brief Interstitial Lung Disease (K-BILD)
Description
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.
Time Frame
baseline, weeks 4, 8, 12 and 24
Title
MCTD participants: Change from baseline in Raynaud's Condition Score (RCS)
Description
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.
Time Frame
baseline, weeks 4, 12 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
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
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Novartis Investigative Site
City
Chang Chun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Novartis Investigative Site
City
Szekesfehervar
State/Province
Fejer
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Bialystok
State/Province
Podlaskie
ZIP/Postal Code
15 707
Country
Poland
Facility Name
Novartis Investigative Site
City
Lublin
ZIP/Postal Code
20-954
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 637
Country
Poland
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
81346
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)
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