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.
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.