Current Clinical Trials

Alzheimer's disease (AD)

Alnylam-EOAD (ALN-APP-001) - recruitment open

Official title

A phase 1 study to evaluate the safety and tolerability of ALN-APP in patients with early onset Alzheimer’s disease (AD)

Purpose of the study

To evaluate the safety (side effects) of a drug called ALN- APP. This drug may have the potential to slow disease progression by reducing production of amyloid protein, which builds up in the brains of people with AD

Participants

Patients with a diagnosis of early onset AD (onset <65 years), with a MMSE score of 21+, who are over the age of 18. Participants must be in good general health, other than AD.

What is involved?

In Part A of the study, participants will make a total of approx. 18 visits over a period of just over a year. Each visit will take approx. 3 to 6 hours depending on the procedures completed at each visit. An overnight stay may also be required. If a participant passes screening, a single dose of ALN-APP or placebo is administered, and they are closely monitored for several months afterwards. Assessments include medical and neurological examinations, memory and thinking questionnaires, blood and urine tests, brain scans (MRI and PET), and a lumbar puncture. Part B will be a multi-dose open-label period including patients previously enrolled in Part A, as well as new participants. This will involve multiple administrations of ALN-APP (all patients will receive the active drug and there will be no placebo). The estimated duration of Part B for each participant is up to 2 years, including a 12 month dosing period (7 separate visits) and 6-12 month follow-up period (at least 2-3 visits).

ACI-35-182 - recruitment closed

Official title
Phase Ib/IIa Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses of Anti-Tau Vaccines in Early Alzheimer’s disease

Purpose of the study
To evaluate the safety and effects on the body of two study vaccines, ACI-35.030 and JACI-35.054, in patients with early Alzheimer’s Disease. The study vaccines have been designed to remove an abnormal form of a protein called Tau which builds up in the brain in Alzheimer’s disease. It is hoped that the reduction in build up of the abnormal Tau proteins will slow down progression of the disease.

Participants
Patients with early Alzheimer’s Disease (AD), or Mild Cognitive Impairment (MCI) due to AD, with a MMSE score of 22 and above, who are aged between 50 and 75 years old

What is involved
Participation in the study will last up to 80 weeks (around 1.5 years) in total. The study consists of 3 periods - screening period (up to 42 days); treatment period (50 weeks) and safety follow-up period (24 weeks). There will be up to 18 visits to see your study doctor in hospital (study visits will last between 4 and 24 hours, depending on what procedures are being carried out at the visit). During the 50-week treatment period, participants will receive 4 administrations of the study vaccine or placebo. Assessments include physical and neurological examinations, ECG, blood and urine tests, interviews and questionnaires, memory and thinking tests, brain scans (MRI) and lumbar puncture.

INVOKE (Alector, AL002-2) - recruitment closed

Official title
A Phase 2 Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of AL002 in Participants with Early Alzheimer’s Disease

Purpose of the study
To test the efficacy and safety of a new investigational drug, AL002, in patients with Early Alzheimer’s disease. AL002 is an antibody which interacts with a receptor called TREM2 to increase production of microglia, the immune cells of the brain. Microglia are thereby promoted to reduce the build-up of abnormal, disease-causing proteins in the brain that are associated with Alzheimer’s disease, aiming to slow disease progression.

Participants
Patients with early Alzheimer’s Disease (AD), or Mild Cognitive Impairment (MCI) due to AD, with a MMSE score of 22 and above, who are aged between 50 and 85 years old

What is involved
Participants will make a total of up to approximately 32 visits to the study site over about 28 months; each visit will take approximately 3 to 6 hours depending on the procedures completed at each visit. The drug/placebo is administered monthly by intravenous (IV) injection, for up to 22 months. Participants will visit us at the study centre for drug/placebo administration, and for assessments including medical and neurological examinations, memory and thinking questionnaires, blood and urine tests, brain scans (MRI and PET), and lumbar puncture.

DESPIAD - recruitment closed

Official title
DEpletion of Serum amyloid P component In Alzheimer’s Disease.

Randomized, placebo-controlled, phase IIb trial of SAP depletion by miridesap in mild Alzheimer’s disease.

Purpose of the study
To confirm the safety of a medication called miridesap and investigate whether it can slow down the progression of Alzheimer’s disease. Miridesap targets a protein called “Serum Amyloid P Component” (SAP) that is increased in the brains of people with Alzheimer’s disease. SAP sticks to the amyloid plaques which in turn stops the plaques from breaking down and directly damages brain cells which may contribute to the development of Alzheimer’s disease. 

Participants
Patients with a diagnosis of mild Alzheimer’s disease, with a MMSE score of 18 or above, who are over the age of 50.

What is involved
The trial is 14 months in duration. For a maximum of 12 months, participants will receive either the active medication or a placebo by subcutaneous (under the skin) injections using a small syringe with a very fine needle. Injections are self-administered (or administered by a study partner) at home, 3 times daily. Participants will also be asked to attend study visits at the study centre where a number of assessments will take place. Assessments include physical and neurological examinations, ECG, blood and urine tests, interviews and questionnaires, memory and thinking tests, brain scans (MRI and PET), and lumbar puncture.

IONIS-AD - recruitment closed

Official title
A Phase I, Randomized, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Intrathecally Administered ISIS 814907 in Patients with Mild Alzheimer’s Disease 

Purpose of the study
To evaluate the safety (side effects) of a drug called ISIS 814907. This drug may have the potential to slow disease progression by reducing production of a protein called tau which builds up in the brains of people with Alzheimer’s disease. Participants are treated with the study drug or placebo.

Participants
This study is now fully recruited.

What is involved
Participants received 4 intrathecal injections (via lumbar puncture) of the study drug or the placebo, with 28 days between each injection. Total study participation was approx. 44 weeks, which included up to 19 visits to the study clinic and 6 phone calls from the study staff. Doctors and staff members evaluated participants through various tests and assessments; including neurological and physical examinations, blood and urine tests, ECG, memory and thinking assessments, brain scans (MRI and PET), and lumbar puncture.

This study is currently in open-label extension phase.

EMBARK - recruitment closed

Official title
Phase 3b Open-Label Study of BIIB037 (aducanumab) in Subjects with Alzheimer’s disease Who Had Previously Participated in the Aducanumab Trials

Purpose of the study
Amyloid plaques accumulate in the brains of patients with Alzheimer’s disease (AD) and this is thought to contribute to the neuronal damage and symptoms of AD. Aducanumab is an antibody which binds to amyloid and helps to clear this protein from the brain. The purpose of this study is to evaluate the safety and tolerability of high dose aducanumab for a longer period than has been tested in previous trials of the drug. This study will also look at whether aducanumab improves participants’ thinking, memory and daily activities, how aducanumab affects biomarkers of disease, and pharmacokinetics. 

Participants
This study is now fully recruited.

What is involved
The study will last for about 2.5 years. Participants will have monthly administration of the study drug by intravenous (IV) infusion for approx. 2 years. Participants will also have examinations, safety assessments, interviews and questionnaires on memory and thinking, brain scans (MRI and PET), blood and urine tests, and lumbar puncture.

ImmunoBrain - recruitment open

Official title

A first in human study to evaluate the safety, tolerability and pharmacokinetics of IBC-Ab002 in persons with early Alzheimer’s disease (AD).

Purpose of the study

To investigate the safety (side effects) of a new drug, IBC-Ab002, in patients with early AD. IBC-Ab002 is an antibody which may help suppress age-related immune system decline by blocking certain immune system pathways that cause age-related impairment, slowing progression of AD.

Participants

Patients with a diagnosis of early Alzheimer’s disease (AD), with a MMSE score of 20-26, who are between 50 and 80 years of age. Participants must be in good general health, other than AD.

What is involved?

This study will be carried out in 2 parts; Part A and Part B. In Part A, a single dose of study medication is given. Part B will begin approximately 3 months later, and 3 doses of study drug will be given 3 months apart. The drug or placebo is administered via IV infusion. Total participation in this study will include approx. 23 visits to the study site over a period of just over a year. Participants will visit us for drug/placebo administration, and also for assessments including medical and neurological examinations, memory and thinking questionnaires, blood and urine tests, brain scans (MRI and PET), and lumbar puncture.

Dominantly Inherited Alzheimer’s Disease (DIAD), or familial Alzheimer’s disease (fAD)

DIAN-TU-001 (E2814 Secondary Prevention Tau NexGen) - recruitment open

Official title

A Phase II/III multicenter randomized, double-blind, placebocontrolled platform trial of potential disease modifying therapies utilizing biomarker, cognitive, and clinical endpoints in Dominantly Inherited Alzheimer’s Disease

Participants

Patients who have Dominantly Inherited Alzheimer’s Disease (DIAD) and are -10/+10 years from age of onset. Participants must know that they are gene positive because there will be open-label administration of lecanemab. Participants must also have a CDR global score of 1 or less.

What is involved?

There are 2 cohorts:

• Cohort 1 is for symptomatic gene carriers. Participants will start on lecanemab which will be administered via IV infusion every 2 weeks. After 6 months, participants will additionally be dosed with the trial drug E2814 or a placebo, administered via IV every 4 weeks.
• Cohort 2 is for asymptomatic gene carriers. Participants will start on the trial drug E2814 or a placebo administered via IV every 4 weeks. After 1 year, lecanemab will additionally be administered via IV every 2 weeks. The study duration is 4-7 years and continues until the last participant who joins the study has reached the end of year 4. Participants will visit us for drug/placebo administration, and also for assessments including medical and neurological examinations, memory and thinking questionnaires, blood and urine tests, brain scans (MRI and PET), and lumbar puncture.

DIAN-TU Cognitive run-in phase - recruitment closed

Official title
Dominantly Inherited Alzheimer’s Disease Network treatment trial (DIAN-TU) 

Purpose of the study
During the current phase of this trial (Cognitive run-in), those participating will be monitored with a number of cognitive and memory tests for up to two years while new drugs are identified for further interventional arms of the trial. These drugs will be targeting Tau protein, which alongside amyloid is known to be critical in development of Alzheimer’s Disease. Eligible individuals in the cognitive run-in will have the option to be screened for drug trials whenever the new drugs are available. 

Participants
Open to individuals both at risk of, and mildly affected by familial Alzheimer’s disease (fAD). This study is currently recruiting anyone over the age of 18 years who has received either a positive genetic test, or is not aware of their genetic mutation.

What is involved
There are approx. 7 short study visits per year required, involving cognitive tests each time. Each year, visits will be 1-2 full days and will include blood sample, MRI and TauPET scan in a proportion of participants. Patients and families are kept up to date and asked their opinions throughout, via webinars and patient conference.

EISAI - recruitment closed

Official title
EISAI E2814-G000-301

An Open-Label Phase 1b/2 Study to Assess Safety and Target Engagement of E2814 in Subjects with Mild to Moderate Cognitive Impairment due to Dominantly Inherited Alzheimer’s Disease

Purpose of the study
To evaluate the safety and target engagement of the investigational study drug, E2814. Accumulation of protein deposits of a substance called Tau in the brain cells may cause Alzheimer’s disease. E2814 is an antibody that binds to tau protein to inhibit further tau accumulation and accelerate its clearance from the brain. 

Participants
Individuals aged 18 to 80 years old who have a confirmed diagnosis of Dominantly Inherited Alzheimer’s Disease (DIAD) (mutation positive for PSEN1, APP or PSEN2 gene that is associated with DIAD).

What is involved
Monthly visits to the study centre for 31 months. The study drug will be administered monthly by intravenous infusion. Participants will also be required to have physical and neurological examinations, blood and urine tests, ECG, questionnaires, memory and thinking tests, brain scans (MRI and PET), and lumbar puncture. 

Frontotemporal dementia (FTD)

INFRONT-2 (AL001-2) - recruitment closed

Official title
A Phase 2 Open-Label Study to Evaluate the Safety and Tolerability of AL001 in Heterozygous Carriers of Granulin or C9orf72 Mutations Causative of Frontotemporal Dementia

Purpose of the study
To see how safe and well-tolerated the experimental drug AL001 is when given intravenously to participants with a mutation in the gene for Granulin (GRN) or C9orf72, which causes frontotemporal dementia (FTD). Mutations such as GRN and C9orf72 cause accumulation of a protein called TDP-43 in the brain, leading to disruption of brain activity, and neurodegeneration. AL001 prevents the breakdown of another protein, Progranulin, which has been found to reduce TDP-43 in non-clinical studies. Therapeutics targeted at reducing TDP-43 may slow the progression of disease in FTD.

Participants
This study will enrol symptomatic and asymptomatic participants with a GRN mutation who completed the AL001-1 study, as well as symptomatic patients with a GRN or C9orf72 mutation who have not had AL001 before.

What is involved
Participants will receive up to 13 doses of AL001 over a 48 week period. Study procedures will include blood sampling, adverse event monitoring, ECG, blood pressure, physical and neurological examinations, lumbar puncture, questionnaires, and MRI. 

INFRONT-3 (Alector, AL001-3) - recruitment open

Official title
A Phase 3, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AL001 in Individuals at Risk for or With Frontotemporal Dementia Due to Heterozygous Mutations in the Progranulin Gene

Purpose of the study
Alector, Inc. is studying AL001 as a new experimental drug for frontotemporal dementia (FTD) caused by mutations in the progranulin gene. These mutations reduce progranulin levels in the body and may lead to symptoms of FTD. The purpose of the phase 3 study is to learn whether increasing progranulin levels with treatment with AL001 will delay onset of symptoms or slow disease progression, when compared to a placebo (a solution that contains no active AL001 drug).

Participants
Open to participants who have been diagnosed with FTD and have a progranulin gene mutation OR have a progranulin gene mutation and are at risk of developing FTD symptoms as evidenced by a biomarker.

What is involved
AL001 or placebo will be administered every 4 weeks by an intravenous (IV) infusion. Assessments will include regular medical examinations, blood tests, brain imaging (MRI), and completion of questionnaires. All participants will be in the study about 2 years and will need to visit the study site at least once a month during this time. Participants who complete the study and who meet the criteria will be eligible to continue to the optional Open Label Extension, during which all participants will receive AL001.