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NCT03952806: M-STAR

Study of BHV-3241 in Participants With Multiple System Atrophy

Completed Phase 3 Results posted Last updated 29 September 2023
What this trial tests

Phase 3 trial testing Verdiperstat in Multiple System Atrophy in 421 participants. Completed in 30 June 2022.

Timeline
29 July 2019
Primary endpoint
29 July 2021
30 June 2022

Quick facts

Lead sponsorBiohaven Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment421
Start date29 July 2019
Primary completion29 July 2021
Estimated completion30 June 2022
Sites48 locations across France, Italy, Austria, United Kingdom, Germany, United States

Drugs / interventions tested

Conditions studied

Sponsor

Biohaven Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 40 to 80, any sex, with Multiple System Atrophy. 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.

Change From Baseline in the Modified UMSARS Score at Week 48 Primary · Baseline and Week 48

UMSARS - clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination), Part IV (Global Disability Scale). Modified UMSARS is composed of subset of 9 items from original UMSARS Part I and Part II. Responses are measured on 4-point scale ranged from 0-3, where 0= no/mild impairment, 1= moderate impairment, 2= severe impairment, 3=complete impairment. Total modified UMSARS score is sum of these 9 items, score range from 0 to 27. Higher scores indicate greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase5.204.52 – 5.89
Placebo - Randomization Phase4.854.19 – 5.51
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Primary · Up to 100 weeks

An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a

TEAE
GroupValue95% CI
Verdiperstat - Randomization Phase160
Placebo - Randomization Phase156
Verdiperstat - Randomization Phase/ Verdiperstat - OLE Phase95
Placebo - Randomization Phase/ Verdiperstat - OLE Phase112
Serious TEAE
GroupValue95% CI
Verdiperstat - Randomization Phase44
Placebo - Randomization Phase29
Verdiperstat - Randomization Phase/ Verdiperstat - OLE Phase30
Placebo - Randomization Phase/ Verdiperstat - OLE Phase27
Clinical Global Impression of Improvement (CGI-I) Score at Week 48 Secondary · Week 48

The CGI-I is a clinician-rated scale measuring the change in the participant's clinical status from a specific point in time. It is scored on a 7- point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change. Higher scores indicate greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase5.074.92 – 5.21
Placebo - Randomization Phase5.145.00 – 5.27
Change From Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Motor Subscale at Week 48 Secondary · Baseline and Week 48

The MSA-QoL is a participant-rated scale that was designed to measure health-related quality of life specifically in MSA. It assesses activities of daily living and has subscales for motor, nonmotor, and emotional/social domains. The MSA-QoL motor subscale includes 14 items. The response to each question ranges from 0= no problem, to 4= extreme problem, with a total scale ranging from 0-56. Higher scores indicates higher impact of the disease on the aspect measured by each subscale.

GroupValue95% CI
Verdiperstat - Randomization Phase13.8310.97 – 16.69
Placebo - Randomization Phase13.4510.72 – 16.18
Change From Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Non-motor Subscale at Week 48 Secondary · Baseline and Week 48

The MSA-QoL is a participant-rated scale that was designed to measure health-related quality of life specifically in MSA. It assesses activities of daily living and has subscales for motor, nonmotor, and emotional/social domains. The MSA-QoL nonmotor subscale includes 12 items. The response to each question ranges from 0= no problem, to 4= extreme problem, with a total scale ranging from 0-48. Higher scores indicates higher impact of the disease on the aspect measured by each subscale.

GroupValue95% CI
Verdiperstat - Randomization Phase7.524.93 – 10.11
Placebo - Randomization Phase5.563.07 – 8.04
Change From Baseline in UMSARS Part I and Part II Total Score at Week 48 Secondary · Baseline and Week 48

The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review with 12 questions), Part II (Motor Examination with 14 questions), Part III (Autonomic Examination), and Part IV (Global Disability Scale). UMSARS Part I and Part II responses are measured on a 5-point scale ranging from 0 to 4, where 0= no impairment, 1= mild impairment, 2= moderate impairment, 3= severe impairment, 4=complete impairment. Each subscale score is a sum of its items and total score is sum of all 26 items, score range from 0 to 104. Higher scores indicates greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase12.0010.37 – 13.63
Placebo - Randomization Phase11.349.77 – 12.90
Change From Baseline in Patient Global Impression of Severity (PGI-S) at Week 48 Secondary · Baseline and Week 48

The PGI-S is a participant-rated scale that measures how participants perceive the severity of their illness. The PGI-S is a 1-item questionnaire on a 4-point scale ranging from 1 to 4, where, 1 = normal, 2 = mild, 3 = moderate, 4 = severe. Higher scores indicate greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase0.330.23 – 0.42
Placebo - Randomization Phase0.270.18 – 0.36
Change From Baseline in Clinical Global Impression of Severity (CGI-S) at Week 48 Secondary · Baseline and Week 48

The CGI-S is a clinician-rated scale measuring the severity of the participant's illness. It is scored on a 7- point scale ranging from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). Higher scores indicate greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase0.790.66 – 0.92
Placebo - Randomization Phase0.780.66 – 0.90
Change From Baseline in UMSARS Part III at Week 48 (Blood Pressure (BP) Only) Secondary · Baseline and Week 48

The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part III of UMSARS was analyzed. Part III of the UMSARS is an Autonomic Exam, consisting of Supine and Standing Systolic and Diastolic Blood Pressure, Heart rate and presence Orthostatic Symptoms. Only change in Orthostatic Blood Pressure reported.

Change in Orthostatic Systolic BP
GroupValue95% CI
Verdiperstat - Randomization Phase-2.18-5.90 – 1.55
Placebo - Randomization Phase-3.09-6.63 – 0.44
Change in Orthostatic Diastolic BP
GroupValue95% CI
Verdiperstat - Randomization Phase-2.87-5.13 – -0.61
Placebo - Randomization Phase-2.54-4.70 – -0.38
Change From Baseline in UMSARS Part III at Week 48 (Heart Rate (HR) Only) Secondary · Baseline and Week 48

The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part III of UMSARS was analyzed. Part III of the UMSARS is an Autonomic Exam, consisting of Supine and Standing Systolic and Diastolic Blood Pressure, Heart rate and presence Orthostatic Symptoms. Only change in Orthostatic Heart Rate reported.

GroupValue95% CI
Verdiperstat - Randomization Phase0.20-1.48 – 1.87
Placebo - Randomization Phase-0.68-2.27 – 0.91
Change From Baseline in UMSARS Part IV at Week 48 Secondary · Baseline and Week 48

The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part IV of UMSARS was analyzed. Part IV was measured on a 5-point scale ranging from 1= Completely independent. Able to do all chores with minimal difficulty or impairment. Essentially normal. Unaware of any difficulty, to 5= Totally dependent and helpless. Bedridden. Higher scores indicate greater impairment.

GroupValue95% CI
Verdiperstat - Randomization Phase0.820.69 – 0.96
Placebo - Randomization Phase0.850.72 – 0.99

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAEs were reported from first dose of study drug and prior to 30 days after the last dose of study drug, maximum of 100 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Verdiperstat - Randomization Phase
Serious: 44/168 (26%)
Deaths: 11/168
Placebo - Randomization Phase
Serious: 29/168 (17%)
Deaths: 5/168
Verdiperstat - Randomization Phase/Verdiperstat - OLE Phase
Serious: 30/123 (24%)
Deaths: 12/123
Placebo - Randomization Phase/Verdiperstat - OLE Phase
Serious: 27/140 (19%)
Deaths: 10/140

Serious adverse events (101 terms)

ReactionSystemVerdiperstat - Randomizati…Placebo - Randomization Ph…Verdiperstat - Randomizati…Placebo - Randomization Ph…
Urinary tract infectionInfections and infestations
PneumoniaInfections and infestations
UrosepsisInfections and infestations
COVID-19 pneumoniaInfections and infestations
Pneumonia aspirationInfections and infestations
SepsisInfections and infestations
Multiple system atrophyNervous system disorders
FallInjury, poisoning and procedural complications
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
Myocardial infarctionCardiac disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
SyncopeNervous system disorders
Ischaemic strokeNervous system disorders
Clavicle fractureInjury, poisoning and procedural complications
Femoral neck fractureInjury, poisoning and procedural complications
DysphagiaGastrointestinal disorders
Deep vein thrombosisVascular disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Head injuryInjury, poisoning and procedural complications
COVID-19Infections and infestations
Clostridial sepsisInfections and infestations
Clostridium difficile colitisInfections and infestations
DiverticulitisInfections and infestations
Herpes zosterInfections and infestations
Other adverse events (20 terms — click to expand)

ReactionSystemVerdiperstat - Randomizati…Placebo - Randomization Ph…Verdiperstat - Randomizati…Placebo - Randomization Ph…
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
HeadacheNervous system disorders
DizzinessNervous system disorders
ConstipationGastrointestinal disorders
Balance disorderNervous system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Gait disturbanceGeneral disorders
Oedema peripheralGeneral disorders
COVID-19Infections and infestations
Orthostatic hypotensionVascular disorders
DepressionPsychiatric disorders
SyncopeNervous system disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
RashSkin and subcutaneous tissue disorders
Blood thyroid stimulating hormone increasedInvestigations
AstheniaGeneral disorders

Most-reported serious reactions: Urinary tract infection, Pneumonia, Urosepsis, COVID-19 pneumonia, Pneumonia aspiration, Sepsis, Multiple system atrophy, Fall.

Data from ClinicalTrials.gov NCT03952806 adverse events section.

Sponsor's own description

The purpose of this study is to compare the efficacy of verdiperstat (BHV-3241) versus placebo in participants with Multiple System Atrophy

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.
    Gao C, Jiang J, Tan Y, Chen S. · · 2023 · cited 998× · PMID 37735487 · DOI 10.1038/s41392-023-01588-0
  2. Baseline Clinical and Blood Biomarkers in Patients With Preataxic and Early-Stage Disease Spinocerebellar Ataxia 1 and 3.
    Tezenas du Montcel S, Petit E, Olubajo T, Faber J, et al · · 2023 · cited 31× · PMID 36797067 · DOI 10.1212/wnl.0000000000207088
  3. Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials.
    Street D, Jabbari E, Costantini A, Jones PS, et al · · 2023 · cited 30× · PMID 36975168 · DOI 10.1093/brain/awad105
  4. MRI Shrimp Sign in Cerebellar Progressive Multifocal Leukoencephalopathy: Description and Validation of a Novel Observation.
    Adra N, Goodheart AE, Rapalino O, Caruso P, et al · · 2021 · cited 28× · PMID 33985948 · DOI 10.3174/ajnr.a7145
  5. Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
    Inghardt T, Antonsson T, Ericsson C, Hovdal D, et al · · 2022 · cited 26× · PMID 36005476 · DOI 10.1021/acs.jmedchem.1c02141
  6. The Unified Multiple System Atrophy Rating Scale: Status, Critique, and Recommendations.
    Krismer F, Palma JA, Calandra-Buonaura G, Stankovic I, et al · · 2022 · cited 25× · PMID 36074648 · DOI 10.1002/mds.29215
  7. Update on the Treatment of Ataxia: Medication and Emerging Therapies.
    Perlman SL. · · 2020 · cited 21× · PMID 33021724 · DOI 10.1007/s13311-020-00941-3
  8. The frequency of non-motor symptoms in SCA3 and their association with disease severity and lifestyle factors.
    Hengel H, Martus P, Faber J, Giunit P, et al · · 2023 · cited 20× · PMID 36324033 · DOI 10.1007/s00415-022-11441-z

Verify or expand the search:

Other trials of Verdiperstat

Trials testing the same drug.

Other recruiting trials for Multiple System Atrophy

Currently open trials in the same condition.

Other Biohaven Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03952806.

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