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NCT04988087

A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)

Terminated Phase 2 Results posted Last updated 9 October 2024
What this trial tests

Phase 2 trial testing MHV370 in Sjogren Syndrome in 30 participants. Terminated before completion.

Timeline
30 November 2021
Primary endpoint
7 February 2023
7 March 2023

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment30
Start date30 November 2021
Primary completion7 February 2023
Estimated completion7 March 2023
Sites10 locations across Taiwan, Germany, Poland, Hungary, China, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Sjogren Syndrome or Mixed Connective Tissue Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

SjS Participants: Change From Baseline in Eular Sjögren's Disease Activity Index (ESSDAI) After 24 Weeks of Treatment Primary · Baseline, Week 24

The ESSDAI is an established disease outcome measure for Sjögren's syndrome that classifies disease activity in 3-4 levels according to their severity (i.e., no, low, moderate, high), over each of 12 organ-specific domains. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The score range is 0 - 123, where a higher ESSDAI score indicates more severe symptoms. A negative change score from baseline indicates improvement.

GroupValue95% CI
Placebo - SjS-4.39± 2.41
MCTD Participants: Change From Baseline in Physician's Global Assessment Scale (PhGA) After 24 Weeks of Treatment Primary · Baseline, Week 24

The physician's global assessment scale is used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). A negative change score from baseline indicates improvement. Only participants with evaluable records are included.

GroupValue95% CI
MHV370 200mg - MCTD-62.00-62.00 – -62.00
SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State Secondary · pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

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.

GroupValue95% CI
MHV370 200mg - SjS278± 85.7
MHV370 200mg - MCTD194
SjS and MCTD Participants: Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours (AUC0-6h) of MHV370 Secondary · pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

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.

GroupValue95% CI
MHV370 200mg - SjS1060± 462
MHV370 200mg - MCTD742
SjS and MCTD Participants: Time to Reach Maximum Plasma Concentrations (Tmax) of MHV370 at Steady State Secondary · pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4

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.

GroupValue95% CI
MHV370 200mg - SjS1.501.00 – 4.00
MHV370 200mg - MCTD2.00
SjS and MCTD Participants: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Secondary · Baseline, Weeks 4, 8, 12, 20 and 24

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 indi

Week 4
GroupValue95% CI
MHV370 200mg - SjS0.13± 3.271
Placebo - SjS-1.58± 6.052
MHV370 200mg - MCTD15.50± 9.192
Placebo - MCTD-3.00
Week 8
GroupValue95% CI
MHV370 200mg - SjS3.14± 5.928
Placebo - SjS-2.80± 4.185
MHV370 200mg - MCTD20.00± 7.071
Placebo - MCTD-2.00
Week 12
GroupValue95% CI
MHV370 200mg - SjS-1.25± 6.702
Placebo - SjS2.71± 8.826
MHV370 200mg - MCTD20.00
Week 20
GroupValue95% CI
MHV370 200mg - SjS-9.42
Placebo - SjS4.80± 8.758
MHV370 200mg - MCTD23.00
Week 24
GroupValue95% CI
Placebo - SjS5.75± 10.782
MHV370 200mg - MCTD30.00
SjS and MCTD Participants: Change From Baseline in Physician Global Assessment (PhGA) Secondary · Baseline, Weeks 4, 8, 12, 20 and 24

The physician's global assessment scale is used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). A negative change score from baseline indicates improvement.

Week 4
GroupValue95% CI
MHV370 200mg - SjS-1.75± 12.658
Placebo - SjS-5.25± 11.185
MHV370 200mg - MCTD-20.50± 12.021
Placebo - MCTD-15.00
Week 8
GroupValue95% CI
MHV370 200mg - SjS2.57± 12.608
Placebo - SjS-8.90± 11.474
MHV370 200mg - MCTD-39.00± 18.385
Placebo - MCTD-12.50
Week 12
GroupValue95% CI
MHV370 200mg - SjS-4.00± 20.559
Placebo - SjS-19.43± 14.328
MHV370 200mg - MCTD-66.00
Week 20
GroupValue95% CI
MHV370 200mg - SjS3.00
Placebo - SjS-14.60± 22.423
MHV370 200mg - MCTD-64.00
Week 24
GroupValue95% CI
Placebo - SjS-30.75± 19.534
MHV370 200mg - MCTD-62.00
SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI) Secondary · Baseline, Weeks 4, 8, 12, 20 and 24

The ESSDAI is an established disease outcome measure for Sjögren's syndrome that classifies disease activity in 3-4 levels according to their severity (i.e., no, low, moderate, high), over each of 12 organ-specific domains. 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.

Week 4
GroupValue95% CI
MHV370 200mg - SjS-0.25± 1.753
Placebo - SjS-3.67± 9.355
Week 8
GroupValue95% CI
MHV370 200mg - SjS0.57± 6.528
Placebo - SjS-4.80± 11.487
Week 12
GroupValue95% CI
MHV370 200mg - SjS-3.00± 4.583
Placebo - SjS-3.43± 7.656
Week 20
GroupValue95% CI
MHV370 200mg - SjS-2.00
Placebo - SjS0.00± 14.629
Week 24
GroupValue95% CI
Placebo - SjS-0.25± 11.117
SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI) Secondary · baseline, weeks 4, 8, 12, 20 and 24

The ESSPRI is an established disease outcome measure for Sjögren's syndrome. The ESSPRI is a patient-reported, subjective symptom index which consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). The participant can assess severity of symptoms they experience on a single numerical scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable) for each of the three domains. The overall ESSPRI score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum s

Week 4
GroupValue95% CI
MHV370 200mg - SjS-0.12± 0.354
Placebo - SjS-0.53± 1.105
Week 8
GroupValue95% CI
MHV370 200mg - SjS-0.67± 0.793
Placebo - SjS-0.37± 1.511
Week 12
GroupValue95% CI
MHV370 200mg - SjS-0.42± 0.500
Placebo - SjS-1.38± 1.976
Week 20
GroupValue95% CI
MHV370 200mg - SjS-0.17
Placebo - SjS-2.20± 1.865
Week 24
GroupValue95% CI
Placebo - SjS-2.00± 2.000
SjS Participants: Change From Baseline to the Salivary Flow Rate Secondary · Baseline, Weeks 4, 12 and 24

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.

Week 4
GroupValue95% CI
MHV370 200mg - SjS0.162± 0.2735
Placebo - SjS-0.127± 0.7914
Week 12
GroupValue95% CI
MHV370 200mg - SjS0.144± 0.2109
Placebo - SjS0.183± 0.3944
Week 24
GroupValue95% CI
Placebo - SjS0.564± 0.9193
SjS Participants: Change From Baseline to the Schirmer's Test Secondary · Baseline, Week 4, 12 and 24

Schirmer's test is used to determine whether the eye produces enough tears to keep it moist especially for those who suffer from dry eye syndrome. A strip is placed in the lower eyelid for 5 minutes to assess tear production. After 5 minutes, the filter paper is removed and the distance between the leading edge of wetness and the initial fold is measured, using a millimeter ruler. Tear deficiency is defined as \<5 mm wetting of the paper after 5 minutes.

Week 4, right eye
GroupValue95% CI
MHV370 200mg - SjS-1.5± 4.87
Placebo - SjS0.0± 3.59
Week 12, right eye
GroupValue95% CI
MHV370 200mg - SjS-1.0± 2.16
Placebo - SjS5.3± 8.81
Week 24, right eye
GroupValue95% CI
Placebo - SjS-3.0± 6.32
Week 4, left eye
GroupValue95% CI
MHV370 200mg - SjS1.1± 1.96
Placebo - SjS1.6± 6.01
Week 12, left eye
GroupValue95% CI
MHV370 200mg - SjS2.0± 1.83
Placebo - SjS4.9± 12.50
Week 24, left eye
GroupValue95% CI
Placebo - SjS-1.0± 2.94
SjS Participants: Sjögren's Tool for Assessing Response (STAR) Response Over Time up to Week 24 Secondary · Baseline, Week 4, 12 and 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: * Systemic activity, if decrease in clin ESSDAI ≥ 3 points: 3 points * Patient reported outcome, if decrease in ESSPRI ≥ 1 point or 15%: 3 points * Lacrimal gland function (assessed by Schirmer's test), if abnormal score at baseline: increase ≥ 5 mm from baseline OR if normal score at baseline: no change to abnormal: 1 point *

Week 4
GroupValue95% CI
MHV370 200mg - SjS0
Placebo - SjS3
Week 12
GroupValue95% CI
MHV370 200mg - SjS1
Placebo - SjS4
Week 24
GroupValue95% CI
MHV370 200mg - SjS0
Placebo - SjS2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

sjs_MHV
Serious: 0/12 (0%)
Deaths: 0/12
sjs_Placebo
Serious: 0/14 (0%)
Deaths: 0/14
MCTD_MHV
Serious: 0/2 (0%)
Deaths: 0/2
MCTD_Placebo
Serious: 1/2 (50%)
Deaths: 0/2
Total
Serious: 1/30 (3%)
Deaths: 0/30

Serious adverse events (1 terms)

ReactionSystemsjs_MHVsjs_PlaceboMCTD_MHVMCTD_PlaceboTotal
Ovarian cystReproductive system and breast disorders
Other adverse events (82 terms — click to expand)

ReactionSystemsjs_MHVsjs_PlaceboMCTD_MHVMCTD_PlaceboTotal
HeadacheNervous system disorders
COVID-19Infections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
RhinitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Complement factor C3 decreasedInvestigations
HypertriglyceridaemiaMetabolism and nutrition disorders
HyperuricaemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
AnaemiaBlood and lymphatic system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
ExtrasystolesCardiac disorders
PalpitationsCardiac disorders
Sinus bradycardiaCardiac disorders
TinnitusEar and labyrinth disorders
Thyroid massEndocrine disorders
CataractEye disorders
Conjunctival suffusionEye disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Aphthous ulcerGastrointestinal disorders
Dental cariesGastrointestinal disorders
Dry mouthGastrointestinal disorders
DuodenitisGastrointestinal disorders
GastritisGastrointestinal disorders
Hiatus herniaGastrointestinal disorders
Mouth swellingGastrointestinal disorders
NauseaGastrointestinal disorders
Paraesthesia oralGastrointestinal disorders
Parotid gland enlargementGastrointestinal disorders
AstheniaGeneral disorders
Feeling hotGeneral disorders

Most-reported serious reactions: Ovarian cyst.

Data from ClinicalTrials.gov NCT04988087 adverse events section.

Sponsor's own description

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).

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing