A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of Venglustat (GZ/SAR402671) in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation

Study at a glance

From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients With Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant

ClinicalTrials.gov ID

NCT02906020

Acronym / sponsor ID

MOVES-PD / ACT14820

Conditions

Parkinson's Disease

Phase

Phase 2

Study type

Interventional

Recruitment status

TerminatedReason stopped: The topline results of the 52-week double-blind placebo-controlled period were analyzed. The study did not meet the primary or secondary endpoints. Based on these results, the decision was made to halt the long-term follow-up period of the study

Enrolment

273 participants (actual)

Lead sponsor

Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)

Study start

15 Dec 2016 (actual)

Primary completion

18 Dec 2020 (actual)

Study completion

27 May 2021 (actual)

First posted

19 Sep 2016 (estimated)

Results

Posted 28 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Triple blind (participant, investigator, outcomes assessor)

Number of arms

2

Who may qualify

Ages

18 to 80 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the period from the time of first investigational medicinal product [IMP] administration up of 6 weeks after the last administration of the IMP).

2. Part 1: Number of Participants With Abnormal Physical Examination Findings

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Physical examination included following observations/measurements: general appearance; heart, skin, respiratory auscultation; head, eyes, ears, nose, and throat, extremities/joints, and abdomen. New onset of abnormal physical examination was defined as a normal physical examination at Baseline and an abnormal physical examination during the treatment-emergent (TE) period (defined as the period from the time of first IMP administration up of 6 weeks after the last administration of the IMP). Abnormalities in physical examination were based on investigator's evaluation.

3. Part 1: Number of Participants With Abnormal Neurological Examination Findings

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Neurological examination included at least assessments of the participant's cranial nerves, motor system (including muscle atrophy, tone, and power), mental status, deep tendon reflex, sensation, and cerebellar function. Abnormalities in neurological examination were based on investigator's evaluation.

4. Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematology

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for potentially clinically significant abnormalities (PCSA): Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (Male[M]) or <=95 g/L (Female[F]), greater than or equal to (>=) 185 g/L (M) or >=165 g/L (F), Decrease from baseline (DFB) >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) (M) or <=0.32 v/v (F), >=0.55 v/v (M) or >=0.5 v/v (F); Red blood cells (RBC): >=6 Tera/L; Platelets: less than (<) 100 Giga/L, >=700 Giga/L; White blood cells (WBC): <3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]), >=16.0 Giga/L; Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); Lymphocytes: <lower limit of normal (LLN), greater than (>) 4.0 Giga/L; Monocytes: <LLN, >0.7 Giga/L; Basophils: >0.1 Giga/L; Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L).

5. Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for PCSA: Alanine Aminotransferase (ALT): >3 ULN, >5 ULN; Aspartate aminotransferase (AST): >3 ULN; Alkaline phosphatase: >1.5 ULN; Total Bilirubin: >1.5 ULN; ALT and Bilirubin: >3 ULN and >2 ULN; Direct Bilirubin and Bilirubin: >35% and >1.5 ULN.

6. Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L) (adults), >=30% change from baseline, >=100% change from baseline; Blood urea nitrogen: >=17 millimoles (mmol)/L.

7. Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for PCSA: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]); Albumin: <=25 g/L.

8. Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for PCSA: Sodium: <=129 mmol/L, >=160 mmol/L; Potassium: <3 mmol/L, >=5.5 mmol/L and Chloride: <80 mmol/L, >115 mmol/L.

9. Part 1: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

   Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

   Criteria for PCSA: Systolic blood pressure (SBP) supine: <=95 millimeters of mercury (mmHg) and DFB >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg; Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg; SBP (Orthostatic): <=-20 mmHg; DBP (Orthostatic): <=-10 mmHg; Heart rate (HR) supine: <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm; Weight: >=5% DFB; >=5% IFB.

10. Part 1: Number of Participants With Potentially Clinically Significant Ophthalmological Abnormalities

    Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

    Clinically significant observations in left eye, right eye and any eye (any eye among left and right) were assessed by the investigator based on methods like visual acuity, slit lamp examination, examination of the cornea, lens, and retina. Any abnormal clinically significant ophthalmological examination finding (which was present at screening or not) on any eye during the treatment-emergent period corresponded to cornea verticillata, cataract and abnormal overall evaluation

11. Part 1: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities

    Time frame: From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

    Criteria for PCSA: HR: <50 bpm; <50 bpm and DFB >=20 bpm, <40 bpm; >90 bpm, <90 bpm and IFB >=20 bpm, >100 bpm; PR Interval: >200 milliseconds (msec), >200 msec and IFB >=25%, >220 msec; QRS Interval: >110 msec, >110 msec and IFB >=25%, >120 msec; QT Interval: >500 msec; QTc Bazett (QTcB) interval: >450 msec, >480 msec, IFB >30 and <=60 msec, IFB >60 msec; QTc Fridericia (QTc F): >450 msec, >480 msec, IFB >30 and <=60 msec, IFB >60 msec.

12. Part 2: Change From Baseline to Week 52 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II+III Total Score

    Time frame: Baseline to Week 52

    MDS-UPDRS is a multimodal scale consisting of 4 parts. Part II assessed motor experiences of daily living (total score range: 0 to 52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (total score range: 0 to 132). Part III contained 33 scores based on 18 items. In both parts, higher score indicated more severe symptoms. For each question in both parts, numeric score was assigned between 0 to 4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS Total Part II and III score = sum of Part II and III scores with score ranged from 0 (no symptom) to 184 (severe symptoms), where higher scores reflected more severe symptoms of PD. Data for this OM was not planned to be collected and analyzed for Part 1, Part 2: DB period re-randomized participants and Part 2 LTFU period, as pre-specified in protocol.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 37479372Giladi N, Alcalay RN, Cutter G, Gasser T, Gurevich T, Hoglinger GU, Marek K, Pacchetti C, Schapira AHV, Scherzer CR, Simuni T, Minini P, Sardi SP, Peterschmitt MJ. Safety and efficacy of venglustat in GBA1-associated Parkinson's disease: an international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2023 Aug;22(8):661-671. doi: 10.1016/S1474-4422(23)00205-3.
• Derived from this study: PubMed 37050861Schidlitzki A, Stanojlovic M, Fournier C, Kaufer C, Feja M, Gericke B, Garzotti M, Welford RWD, Steiner MA, Angot E, Richter F. Double-Edged Effects of Venglustat on Behavior and Pathology in Mice Overexpressing alpha-Synuclein. Mov Disord. 2023 Jun;38(6):1044-1055. doi: 10.1002/mds.29398. Epub 2023 Apr 12.
• Derived from this study: PubMed 34897099Peterschmitt MJ, Saiki H, Hatano T, Gasser T, Isaacson SH, Gaemers SJM, Minini P, Saubadu S, Sharma J, Walbillic S, Alcalay RN, Cutter G, Hattori N, Hoglinger GU, Marek K, Schapira AHV, Scherzer CR, Simuni T, Giladi N, Sardi SP, Fischer TZ; MOVES-PD Investigators. Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson's Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial. J Parkinsons Dis. 2022;12(2):557-570. doi: 10.3233/JPD-212714.
• Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

52 sites in 16 countries: see every site and its status.