Ambroxol in New and Early DLB, A Phase IIa Multicentre Randomized Controlled Double Blind Clinical Trial

NCT04588285 | Recruiting Phase 2 DMC

• 1 other identifier: 3.4 Date: 11th of March 2024
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 8

Brief Summary

This is a confirmatory investigational medicinal product (IMP) study to investigate the effects on cognition, functional decline and on neuropsychiatric symptoms of the Glucocerebrosidase (GCase) enhancing chaperone ambroxol in participants diagnosed with prodromal and early dementia with Lewybodies (DLB).

Conditions

Dementia With Lewy Bodies

Keywords

Cognitive; Neuropsychiatric; Functional Outcomes; New and Early Patients; Prodromal; Mild Dementia; Lewybodies

Outcome Measures

Primary Outcomes (9)

• Change in the incidence, nature and severity of AE's and SAE's from baseline.

  Change in the number of participants with AE's and SAE's.

  All patient visits including phonecalls trough study completion, planned duration 18 months

• Change in the number of participants with treatment discontinuations and study discontinuation due to AEs from baseline.

  Change from baseline in the number of participants with treatment and/or study discontinuation will be used to demonstrate safety and tolerability

  All patient visits including phonecalls trough study completion, planned duration 18 months

• Change in the number of participants with electrocardiogram (ECG) abnormalities.

  Including QTc interval.

  Through study completion at the following visits: Screening, Baseline, week 4, week 24, week 36, week 52, month 15, and month 18.

• Change in blood analyses from baseline over time abnormalities.

  Change from baseline in number of participants with abnormal changes in clinical laboratory blood tests from baseline over time for safety.

  Through study completion at the following visits: Screening, week 4, week 8, week 24, week 36, week 52, month 15, and month 18.

• Change in MMSE-NR3 (Mini Mental Status Examination, Norwegian revised version) over time.

  To confirm the effect of the IMP ambroxol in participants diagnosed with DLB measured by a defined battery of cognitive tests defining MMSE-NR3 as the primary outcome. The MMSE-NR3 is a screening test for cognitive impairment that spans the visuospatial/executive, naming, memory, attention, language, delayed recall and orientation domains (score range from 0 to 30 points).

  Through study completion at the following visits: Screening, week 24, week 36, week 52, Month 18.

• ADCS-CGIC (Clinician's Global Impression of Change)

  To confirm the effect of the IMP Ambroxol on the rate of functional decline in DLB.

  Through study completion at the following visits: Screening, week 24, week 36, week 52, month 18.

• Change in CDR-SB (Clinical Dementia Rating-Sum of Boxes).

  Measure Rate of decline from screening to study completion at month 18 using CDR-SB.

  Through study completion at the following visits: Screening, week 24, week 36 week 52, Month 18.

• Change NPI (neuropsychiatric inventory)

  To confirm the effect of the IMP Ambroxol on neuropsychiatric symptoms in DLB from screening to study completion at month 18 by using NPI. The NPI is a semistructured clinician interview of caretakers in which the severity and frequency of disturbance in 12 symptom domains is rated. The scoring reflects not only the effect on the patient, but also the extent to which the symptom causes distress in the caregiver. Score 0-144. The higher the score the more disease progression.

  Through study completion at the following visits: Screening, week 24, week 36, week 52, month 18.

• GDS (geriatric depression scale) - 15 items

  To confirm the effect of the IMP Ambroxol on neuropsychiatric symptoms in DLB from screening to study completion at month 18 by using GDS. The Geriatric Depression Scale (GDS) is a 15-item self-report assessment used to identify depression in the elderly. A high score usually always indicates depression and more severe depression.

  Through study completion at the following visits: Screening, week 24, week 36, week 52, month 18.

Secondary Outcomes (4)

• Mayo Sleep Questionnaire (MSQ).

  Through study completion at the following visits: Screening, week 24, week 36, week 52, Month 18.

• Mayo Fluctuation Scale (MFS)

  Through study completion at the following visits: Screening, week 24, week 36, week 52, Month 18.

• Unified Parkinson Disease Rating Scale (UPDRS-III)

  Through study completion at the following visits: Screening, week 8, week 24, week 36, week 52, Month 18.

• Number of falls and related injury

  Through study completion at the following visits: Screening, week 24, week 36, week 52, Month 18.

Study Arms (2)

Ambroxol

EXPERIMENTAL

Oral ambroxol medication, from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 mg BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)).

Drug: Ambroxol

Placebo

EXPERIMENTAL

Oral placebo medication, from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 mg BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)).

Drug: Placebo

Interventions

Placebo DRUG

Oral placebo medication (60 mg) from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 mg BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)

Placebo

Ambroxol DRUG

Oral ambroxol medication (60 mg) from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 mg BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)

Also known as: Mucosolvan

Ambroxol

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female.
• Age ≥ 50 and ≤ 85 years of age.
• Confirmed diagnosis of Dementia with Lewy Bodies (DLB) or Mild Cognitive Impairment in DLB (DLB-MCI).
• MMSE score\>=15
• Able and willing to provide informed consent prior to any study related assessments and procedures at screening visit 1.
• Capable of complying with all study procedures.
• Willing to provide blood samples for genetic analyses of APOE and GBA.
• Willing and able to self-administer or administer by a caregiver oral ambroxol medication, from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)).
• Able to travel to the participating study site.
• A female participant is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 consecutive months of spontaneous amenorrhea, at least 6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) or post tubal ligation. In questionable cases, menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) 25.8 - 134.8 IU/L and oestradiol \< 201 pmol/l at entry.
• Women of child-bearing potential must use accepted contraceptive methods (listed below), and must have a negative serum at screening visit 1 and urine pregnancy tests at subsequent visits if applicable. An additional pregnancy test will be performed, and results obtained, prior to administration of the first dose of ambroxol.
• A female participant is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 consecutive months of spontaneous amenorrhea, at least 6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) or post tubal ligation. In questionable cases, menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) 25.8 - 134.8 IU/L and oestradiol \< 201 pmol/l at entry.
• Women of child-bearing potential must use accepted contraceptive methods (listed below), and must have a negative serum at screening visit 1 and urine pregnancy tests at subsequent visits if applicable. An additional pregnancy test will be performed, and results obtained, prior to administration of the first dose of ambroxol.

You may not qualify if:

• Current treatment with anticoagulants (e.g. warfarin) that might preclude safe completion in the opinion of the Investigator.
• Current use of investigational medicinal product or participation in another interventional clinical trial or who have done so within 30 days prior to the first dose in the current study.
• Exposure to more than three investigational medicinal products within 12 months prior to the first dose in the current study;
• Confirmed dysphagia that would preclude self-administration of ambroxol up to 6 tablets daily for the duration of day 1 to day 550/Month 18.
• Significant known lower spinal malformations or other spinal abnormalities that would preclude lumbar puncture.
• History of known sensitivity to the study medication, ambroxol or its excipients (lactose monohydrate, granulated microcrystalline cellulose, copovidone and magnesium stearate) in the opinion of the investigator that contraindicates their participation.
• History of known rare hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
• History of illegal substance abuse, drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the study.
• Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of the study drug.
• Pregnant or breastfeeding; All participants of child bearing potential in the opinion of the Investigator that would preclude participation in the study and who do not agree to use double-barrier birth control or abstinence while participating in the study and for two weeks following the last dose of study drug;
• Any clinically significant or unstable psychiatric, medical or surgical condition that in the opinion of the PI or PI-delegated clinician may put the participant at risk when participating in the study or may influence the results of the study or affect the participant's ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests.
• Such conditions may include:
• Impaired renal function
• Moderate/Severe hepatic impairment
• A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, pulmonary embolism, coronary revascularisation that occurred within 6 months prior to the screening visit.

Sponsors & Collaborators

• Helse Fonna: lead
• Klinbeforsk: collaborator
• Helse-Bergen HF: collaborator
• University Hospital, Akershus: collaborator
• Helse Stavanger HF: collaborator
• Haraldsplass Deaconess Hospital: collaborator
• University Hospital of North Norway: collaborator
• Oslo University Hospital: collaborator
• St. Olavs Hospital: collaborator

Study Sites (8)

Helse Fonna

Haugesund, Haugesund, 5504, Norway

RECRUITING

Haraldsplass Deaconess Hospital

Bergen, Norway

RECRUITING

University Hospital, Akershus

Hågån, Norway

RECRUITING

University Hospital, Akershus

Lørenskog, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Stavanger University Hospital

Stavanger, Norway

RECRUITING

University Hospital North-Norway

Tromsø, Norway

RECRUITING

Trondheim University Hospital

Trondheim, Norway

RECRUITING

Related Links

• Rongve, A., et al. Demens med Lewylegemer- utredning og behandling. 2017
• Aarsland, D. MULTI-CENTRE COHORT-STUDIES IN LEWY-BODY DEMENTIA. 2015

MeSH Terms

Conditions

Lewy Body Disease

Interventions

Ambroxol

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Study Officials

• Arvid Rongve, Phd

  arvid.rongve@helse-fonna.no

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arvid Rongve, Phd

CONTACT

90548749; arvid.rongve@helse-fonna.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The blinded phase (placebo or ambroxol) will last for 18 months and an open extension with ambroxol will be offered to all participants for one additional year. Randomisation to placebo or ambroxol will be done by the system Viedoc.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant will receive 5 intra-participant dose escalations at 60 mg TID (day 1-7), 120 mg TID (day 8-14), 315 BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550) with ambroxol or placebo for the duration of 18 months.

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: October 19, 2020
• Study Start: May 4, 2021
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): September 15, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (8)