Clinical trial NCT04184063: Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA)
Official title: A Pilot Exploratory, Randomised, Placebo-controlled, Double Blinded, Cross-over , Phase 2a Study to Explore Efficacy and Safety of NBMI Treatment in Patients With Progressive Supranuclear Palsy (PSP) or Multiple System Atrophy (MSA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Progressive Supranuclear Palsy
Multiple System Atrophy
Lead sponsor: EmeraMed
Sponsor class: INDUSTRY
First posted: 2019-12-03
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: In total 20 subjects will be enrolled at one participating site -UMC Ljubljana. The 20 subjects will be treated with placebo and NBMI 300 mg in a cross-over design. In case of subject drop-outs, additional subjects may be enrolled as decided by the Sponsor, to allow for expected number of evaluable subjects in each group.

Detailed description: · The study's primary objective is: To explore the efficacy of 28 days NBMI treatment on motor and non-motor symptoms and heath related quality of life in patients with Progressive Supranuclear Palsy or Multiple Systems Atrophy disease.

The study's secondary objectives are:

* to explore safety and tolerability of 28 day NBMI treatment in patients with Progressive Supranuclear Palsy or Multiple Systems Atrophy.
* to investigate the efficacy of NBMI daily oral administration for 28 days on fatigue in MSA and PSP patients,
* to investigate the efficacy of NBMI daily oral administration for 28 days on depression in MSA and PSP patients.

The study's exploratory aims are:

* to explore the effect of NBMI treatment on patient's brain iron levels as evaluated by MRI imaging,
* to explore the effect of NBMI on brain metabolism with FDG- PET- CT brain imaging,
* to explore the pharmacokinetics of NBMI in patients with PSP or MSA.

Eligibility criteria: Inclusion Criteria:

1. Patient has clinically confirmed documented diagnosis of PSP or MSA, according to the current clinical criteria.
2. Patient has a brain MRI finding consistent with the diagnosis of PSP or MSA at Screening.
3. Patient is aged 40 years to 85 years inclusive at screening age.
4. Patient is fluent in the local language and possesses sufficient auditory and visual capacities to allow neuropsychological testing.
5. Patient and caregiver are able to read and understand informed consent.
6. Patient is on a stable therapy for PSP, MSA for at least 1 month prior to screening visit.
7. If the patient received i.v. amantadine treatment, the last infusion must have been administered at least 6 months prior to the screening (V01).
8. Availability of a caregiver who sufficiently knows the patient and will be able to accompany the patient on the study visits and to participate in study assessments of the patient where required.
9. Female patients are only eligible for the study if they are either surgically sterile or at least 2 years postmenopausal or have a negative result of serum hCG test at screening and apply to criteria no. 10.
10. Female of childbearing potential can only participate in the study if willing to use acceptable, effective methods of contraception during the trial and for three month after the end of trial participation as defined in point 6.7. of this protocol.
11. Male patients must either be surgically sterile or he and his female spouse/partner who is of childbearing potential must be willing to use highly effective methods of contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study.
12. Patient provides written informed consent.

Exclusion Criteria:

1. Known history or presence of clinically significant other neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2. Known or suspected allergy hypersensitivity or idiosyncratic reaction to NBMI or any other drug substances with similar activity.
3. Patient has known contraindication for MRI imaging such as MRI-incompatible metallic endoprosthesis or MRI-incompatible stent implantation or other as judged by the Investigator.
4. Patient has claustrophobia that could prevent MRI imaging
5. History of drug or alcohol addiction requiring treatment.
6. Patient who had previous chronic exposure (within one year before recruitment) to iron from taking preparations/medications for rising iron
7. History of malabsorption within the last year or presence of clinically significant gastrointestinal disease or surgery that may affect drug bioavailability, including but not limited to cholecystectomy.
8. Patient is ridden to bed.
9. Presence of hepatic or renal dysfunction. (SGOT and SGPT and bilirubin \> X2 UNL. creatinine \> 1.5mg/dl)
10. Female patient who is pregnant (serum hCG level consistent with pregnancy diagnosis); or breastfeeding.
11. Participation in a clinical trial that involved administration of an investigational medicinal product within 90 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results.
12. Patient has a history with evidence of cerebrovascular disease (ischemic or haemorrhagic), or diagnosis of possible, probable or definite vascular Parkinsonism or dementia.
13. Have clinically significant abnormal laboratory values (e.g. liver enzymes)
14. Have clinically significant findings from a physical examination (e.g. fever)
15. Patient has claustrophobia that could prevent him from attending MRI imaging

Primary outcomes:
measure: Changes in Progressive Supranuclear Palsy rating Scale (PSPRS) individual scales scores from baseline in PSP patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in FAB individual scales scores from baseline in PSP patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in Unified Multiple System Atrophy Rating Scale (UMSARS) individual scale from baseline in MSA patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in Non-Motor Symptoms assessment scale (NMSS) individual scale from baseline in MSA patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in QOL individual scores from baseline by MSA questionnaire in MSA patients
timeFrame: through study completion, an average of 85 days
measure: Changes in QOL individual scores from baseline by MSA questionnaire in MSA patients using Visual Analog score
timeFrame: through study completion, an average of 85 days
measure: Changes in QOL individual scores from baseline by EQ-5D score in PSP patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
Secondary outcomes:
measure: Changes in Parkinson's Disease Fatigue Score (PFS) score from Baseline - V1 to V2 (D29) and V1 to V5 (D57) in PSP and MSA patients compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in Beck's Depression Inventory (BDI) scale (MSA patients) score from Baseline V1 to V2 (D29) and to V4 (D57) compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes in Geriatric depression scale (GDS) (PSP patients) score from Baseline - V1 to V2 (D29) and to V4 (D57) compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Frequency, type and severity of adverse events compared to placebo treatment .
timeFrame: through study completion, an average of 85 days
measure: Percentage of NBMI-treated patients who develop a response to NBMI.
timeFrame: through study completion, an average of 85 days
Other outcomes:
measure: Changes from baseline in brain metabolism as evaluated with Fluorodeoxyglucose Positron Emission Tomography (FDG PET) CT brain imaging compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Changes from baseline in brain iron levels as detected with Magnetic Resonance Imaging (MRI) imaging methods compared to placebo treatment
timeFrame: through study completion, an average of 85 days
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: Maximum Plasma Concentration [Cmax]
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: AUC0-t
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: AUC0-∞
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: AUC%Extrap,obs
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: t1/2
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: λz
timeFrame: Day 56, 57
measure: Pharmacokinetic parameters derived from plasma concentrations of NBMI: T max
timeFrame: Day 56, 57
Locations:
city: Ljubljana
country: Slovenia
facility: Ukc Ljubljana
Study officials:
affiliation: CRS d.o.o.
name: Tanja Turk, M. Pharm
role: STUDY_DIRECTOR
References: