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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-004937-19 | EudraCT Number |
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Sponsor decision
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MHV370 | Drug | MHV370 for 24 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State | Cmax is the maximum (peak) observed plasma concentration of MHV370 after single dose administration. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. Cmax was determined using non-compartmental methods. |
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Inclusion Criteria:
SjS and MCTD:
• Fully vaccinated with any locally approved COVID-19 vaccination including booster vaccinations if required by local guidelines
SjS:
MCTD:
Exclusion Criteria:
SjS and MCTD:
SjS:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Guangzhou | Guangdong | 510000 | China | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40787733 | Derived | 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. | |
| 40747756 | 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. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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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
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There was a screening period of up to 6 weeks to assess participants eligibility.
Participants took part in 10 investigative sites in 6 countries/regions.
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| ID | Title | Description |
|---|---|---|
| FG000 | MHV370 200mg - SjS | MHV370 200mg oral dose, twice daily. SjS participants. |
| FG001 | Placebo - SjS | Placebo oral dose, twice daily. SjS participants. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 9, 2022 | Jan 16, 2024 |
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| Placebo |
| Drug |
Placebo for 24 weeks |
|
| 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 | The AUC from time zero to the 6-hours post-dose sampling time. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. AUClast was determined using non-compartmental methods. | 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 | Tmax is the time to reach maximum (peak) plasma concentration of MHV370 after single dose administration. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. Tmax was determined using non-compartmental methods. | 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 | The Functional Assessment of Chronic Illness Therapy-Fatigue (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) | 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, Weeks 4, 8, 12, 20 and 24 |
| 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. The score range is 0 - 123, where a higher ESSDAI 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 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. | baseline, weeks 4, 8, 12, 20 and 24 |
| SjS Participants: Change From Baseline to the Salivary Flow Rate | Unstimulated whole salivary fluid secretions were collected over 5 minutes from participants. All assessments were performed at a fixed time of the day to minimize fluctuations related to the circadian rhythm of salivary flow and composition. Participants were instructed not to eat, drink or smoke for 90 minutes before the assessment. The start time and end time of saliva collection were recorded to calculate the salivary flow rate per minute. Only participants with evaluable records are included. | Baseline, Weeks 4, 12 and 24 |
| 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. | Baseline, Week 4, 12 and 24 |
| 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 Domain Point Definition of response. Points are assigned in the following 5 domains, if the corresponding criteria are met:
| Baseline, Week 4, 12 and 24 |
| 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) completed 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 score range is 0-21, 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) | Forced Vital Capacity (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. A positive change from baseline is considered a favorable outcome. | Baseline, Week 12 |
| MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Second (FEV1) of a Forced Breath | FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV1 is considered a favourable outcome. | Baseline, Week 12 |
| MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Two Seconds (FEV2) of a Forced Breath | FEV2 (forced expiratory volume in two seconds) is the amount of air which can be forcibly exhaled from the lungs in the first two seconds of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV2 is considered a favourable outcome. | Baseline, Week 12 |
| MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Three Seconds (FEV3) of a Forced Breath | FEV3 (forced expiratory volume in three seconds) is the amount of air which can be forcibly exhaled from the lungs in the first three seconds of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV3 is considered a favourable outcome. | Baseline, Week 12 |
| MCTD Participants: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) | Diffusing capacity of the lungs for carbon monoxide (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. The outcome is presented as percentage of predicted DLCO value. | Baseline, Week 24 |
| 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. 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) | The Raynaud's Condition score (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 |
| Changchun |
| Jilin |
| 130021 |
| China |
| Novartis Investigative Site | Berlin | 10117 | Germany |
| Novartis Investigative Site | Székesfehérvár | Fejér | 8000 | Hungary |
| Novartis Investigative Site | Debrecen | 4032 | Hungary |
| Novartis Investigative Site | Bialystok | Podlaskie Voivodeship | 15 707 | Poland |
| Novartis Investigative Site | Lublin | 20-954 | Poland |
| Novartis Investigative Site | Warsaw | 02 637 | Poland |
| Novartis Investigative Site | Madrid | 28041 | Spain |
| Novartis Investigative Site | Kaohsiung City | 81346 | Taiwan |
| FG002 | MHV370 200mg - MCTD | MHV370 200mg oral dose, twice daily. MCTD participants. |
| FG003 | Placebo - MCTD | Placebo oral dose, twice daily. MCTD participants. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | MHV370 200mg - SjS | MHV370 200mg oral dose, twice daily. SjS participants. |
| BG001 | Placebo - SjS | Placebo oral dose, twice daily. SjS participants. |
| BG002 | MHV370 200mg - MCTD | MHV370 200mg oral dose, twice daily. MCTD participants. |
| BG003 | Placebo - MCTD | Placebo oral dose, twice daily. MCTD participants. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. The data includes only participants who completed Week 24. Only participants with evaluable records are included. | Posted | Mean | Standard Error | Score on scale | Baseline, Week 24 |
|
|
| ||||||||||||||||||||||||||||
| Primary | 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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. The data includes only participants who completed Week 24. Only participants with evaluable records are included. | Posted | Median | Full Range | Score on scale | Baseline, Week 24 |
|
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| Secondary | SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State | Cmax is the maximum (peak) observed plasma concentration of MHV370 after single dose administration. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. Cmax was determined using non-compartmental methods. | The pharmacokinetic (PK) analysis set included participants with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received MHV370 and with no protocol deviations with impact on PK data. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 |
|
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| Secondary | SjS and MCTD Participants: Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours (AUC0-6h) of MHV370 | The AUC from time zero to the 6-hours post-dose sampling time. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. AUClast was determined using non-compartmental methods. | The pharmacokinetic (PK) analysis set included participants with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received MHV370 and with no protocol deviations with impact on PK data. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | ng*h/mL | pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 |
|
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| Secondary | SjS and MCTD Participants: Time to Reach Maximum Plasma Concentrations (Tmax) of MHV370 at Steady State | Tmax is the time to reach maximum (peak) plasma concentration of MHV370 after single dose administration. Pharmacokinetic (PK) parameters were calculated based on MHV370 plasma concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1.0 ng/mL. Tmax was determined using non-compartmental methods. | The pharmacokinetic (PK) analysis set included participants with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received MHV370 and with no protocol deviations with impact on PK data. Only participants with evaluable records are included. | Posted | Median | Full Range | hours | pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4 |
|
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| Secondary | SjS and MCTD Participants: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale | The Functional Assessment of Chronic Illness Therapy-Fatigue (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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 8, 12, 20 and 24 |
| ||||||||||||||||||||||||||||||
| Secondary | 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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 8, 12, 20 and 24 |
| ||||||||||||||||||||||||||||||
| Secondary | 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. The score range is 0 - 123, where a higher ESSDAI score indicates more severe symptoms. A negative change score from baseline indicates improvement. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 8, 12, 20 and 24 |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | baseline, weeks 4, 8, 12, 20 and 24 |
| ||||||||||||||||||||||||||||||
| Secondary | SjS Participants: Change From Baseline to the Salivary Flow Rate | Unstimulated whole salivary fluid secretions were collected over 5 minutes from participants. All assessments were performed at a fixed time of the day to minimize fluctuations related to the circadian rhythm of salivary flow and composition. Participants were instructed not to eat, drink or smoke for 90 minutes before the assessment. The start time and end time of saliva collection were recorded to calculate the salivary flow rate per minute. Only participants with evaluable records are included. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. | Posted | Mean | Standard Deviation | mL/min | Baseline, Weeks 4, 12 and 24 |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | milimeter | Baseline, Week 4, 12 and 24 |
|
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| Secondary | 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 Domain Point Definition of response. Points are assigned in the following 5 domains, if the corresponding criteria are met:
| The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Missing responses will be treated as non-responders. Only participants with evaluable records are included. | Posted | Count of Participants | Participants | Baseline, Week 4, 12 and 24 |
| |||||||||||||||||||||||||||||||
| Secondary | 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) completed 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 score range is 0-21, where a higher score indicates more severe symptoms. A negative change score from baseline indicates improvement. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 8, 12 and 24 |
| ||||||||||||||||||||||||||||||
| Secondary | MCTD Participants: Change From Baseline in Forced Vital Capacity (FVC) | Forced Vital Capacity (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. A positive change from baseline is considered a favorable outcome. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | liters (L) | Baseline, Week 12 |
|
| |||||||||||||||||||||||||||||
| Secondary | MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Second (FEV1) of a Forced Breath | FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV1 is considered a favourable outcome. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | liters (L) | Baseline, Week 12 |
|
| |||||||||||||||||||||||||||||
| Secondary | MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Two Seconds (FEV2) of a Forced Breath | FEV2 (forced expiratory volume in two seconds) is the amount of air which can be forcibly exhaled from the lungs in the first two seconds of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV2 is considered a favourable outcome. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | liters (L) | Baseline, Week 12 |
|
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| Secondary | MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Three Seconds (FEV3) of a Forced Breath | FEV3 (forced expiratory volume in three seconds) is the amount of air which can be forcibly exhaled from the lungs in the first three seconds of a forced exhalation, measured through spirometry testing. A positive change from baseline in FEV3 is considered a favourable outcome. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | liters (L) | Baseline, Week 12 |
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| Secondary | MCTD Participants: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) | Diffusing capacity of the lungs for carbon monoxide (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. The outcome is presented as percentage of predicted DLCO value. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | percentage of predicted DLCO | Baseline, Week 24 |
|
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| Secondary | 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. Total scores range from 0 to 100, with higher scores representing better health status. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 8, 12 and 24 |
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| Secondary | MCTD Participants: Change From Baseline in Raynaud's Condition Score (RCS) | The Raynaud's Condition score (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. | The pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD/efficacy data. Data from participants who have discontinued treatment early are regarded as missing after the treatment discontinuation. Only participants with evaluable records are included. | Posted | Mean | Standard Deviation | Score on scale | Baseline, Weeks 4, 12 and 24 |
|
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 199 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | sjs_MHV | sjs_MHV | 0 | 12 | 0 | 12 | 12 | 12 |
| EG001 | sjs_Placebo | sjs_Placebo | 0 | 14 | 0 | 14 | 12 | 14 |
| EG002 | MCTD_MHV | MCTD_MHV | 0 | 2 | 0 | 2 | 1 | 2 |
| EG003 | MCTD_Placebo | MCTD_Placebo | 0 | 2 | 1 | 2 | 2 | 2 |
| EG004 | Total | Total | 0 | 30 | 1 | 30 | 27 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Thyroid mass | Endocrine disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Conjunctival suffusion | Eye disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Duodenitis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Mouth swelling | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Parotid gland enlargement | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Swelling | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Allergy to arthropod bite | Immune system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Dacryocanaliculitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Antinuclear antibody increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Complement factor C3 decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Complement factor C4 decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Glomerular filtration rate decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Vertebral foraminal stenosis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypergeusia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cutaneous vasculitis | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2023 | Jan 16, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012859 | Sjogren's Syndrome |
| D008947 | Mixed Connective Tissue Disease |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D014987 | Xerostomia |
| D012466 | Salivary Gland Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D015352 | Dry Eye Syndromes |
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| Male |
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| White |
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| MHV370 200mg - MCTD |
MHV370 200mg oral dose, twice daily. MCTD participants. |
| OG003 | Placebo - MCTD | Placebo oral dose, twice daily. MCTD participants. |
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| Placebo - MCTD |
Placebo oral dose, twice daily. MCTD participants. |
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Placebo oral dose, twice daily. SjS participants.
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