A Phase 3, prospective, randomized, double-blind, placebo-controlled, parallel group, international, multi-center study of rotigotine in combination with rivastigmine in mild to moderate Alzheimer’s disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Santa Lucia IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Oct 2023 → ongoing

Decision date (initial)

2023-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Alzheimer's Drug Discovery Foundation (ADDF)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo (change from Baseline to Week 24 in the FAB);

Secondary objectives 1

1. To evaluate efficacy of rotigotine in combination with rivastigmine on activities of daily living as compared to rivastigmine in combination with placebo (change from Baseline to Week 24 in the ADCS-ADL).

Conditions and MedDRA coding

Mild to moderate Alzheimer's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Men and women (non-childbearing potential, as defined in Appendix 2) with a diagnosis of AD according to IWG criteria 2. Age 50-85 years 3. MRI or computerized tomography (CT) assessment within twelve months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3) 4. Patients who show CSF biomarker data supporting the diagnosis of AD measured within the last 3 years, or patients with a positive Amyloid Pet Scan within the last 3 years will qualify for the study 5. Mild to moderate stage of AD according to MMSE ≥18 and ≤26 6. Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) 7. Evidence of frontal lobe dysfunctions as assessed by FAB ≤14 8. Absence of major depressive disease according to GDS of < 5 9. Formal education for eight or more years 10. Previous decline in cognition for more than six months as documented in patient medical records 11. A caregiver available and living in the same household or interacting with the patient and available if necessary to assure administration of drug 12. Patients living at home or nursing home setting without continuous nursing care 13. General health status acceptable for a participation in a 6-month clinical trial 14. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening 15. No regular intake of prohibited medications. 16. Signed informed consent by the patient, prior to the initiation of any study specific procedure and signed consent of the caregiver

Exclusion criteria 1

1. 1. Failure to perform screening or baseline examinations 2. Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period 3. Clinical, laboratory or neuro-imaging findings consistent with: • other primary degenerative dementia (dementia with Lewy bodies, fronto-temporal dementia, Huntington’s disease, Creutzfeldt-Jakob Disease, Down’s syndrome, etc.); • other neurodegenerative condition (Parkinson’s disease, amyotrophic lateral sclerosis, etc.); • orthostatic hypotension and autonomic disorders • cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter); • other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.); • seizure disorder; • other infectious, metabolic, or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.). 4. A current DSM-V diagnosis of active major depression, schizophrenia, or bipolar disorder 5. Clinically significant, advanced, or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: • chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN); • respiratory insufficiency; • renal insufficiency (serum creatinine >2 mg/dl) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula). In case of creatinine clearance ≤30 mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the patient can be included; • heart disease (myocardial infarction, unstable angina, heart failure, Cardiomyopathy within six months before screening); • bradycardia (heart beat <50/min.) or tachycardia (heart beat >95/min); • hypertension (>180/95) or hypotension (<90/60) requiring treatment with more than three drugs; •AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males >450 and females >470 msec); • uncontrolled diabetes defined by HbA1c >8.5;

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ● to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo (change from Baseline to Week 24 in the FAB);

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Santa Lucia IRCCS

Sponsor organisation

Fondazione Santa Lucia IRCCS

Address

Via Ardeatina 306

City

Rome

Postcode

00179

Country

Italy

Scientific contact point

Organisation

Fondazione Santa Lucia IRCCS

Contact name

Dr. Giacomo Koch

Public contact point

Organisation

Fondazione Santa Lucia IRCCS

Contact name

Francesco Di Lorenzo, MD

Third parties 4

Locations

4 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications