This study will evaluate the efficacy and safety of gantenerumab compared with placebo in patients with early (prodromal to mild) Alzheimer's disease (AD).
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
neurologische aandoeningen, Alzheimer
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy objective of main study: To evaluate the efficacy of
gantenerumab administered by SC injection compared with placebo
The change from baseline (Day 1) to Week 104 in global outcome, as measured by
the CDR-SOB
Primary efficacy objective of the OLE period: To evaluate the long-term safety
and tolerability of SC gantenerumab in patients with early AD
Protocol version 4: endpoint timeline become week 116
The ongoing impact of the COVID-19 pandemic on the study procedures will be
closely monitored, and if necessary, the double-blind treatment period will be
further extended by another 12 weeks and times will be adjusted accordingly.
Secondary outcome
Secundary efficacy objective: To evaluate the efficacy of gantenerumab versus
placebo on cognition and function
The change from baseline to Week 104 in cognition
and/or function, as measured by:
* MMSE total score
* ADAS-Cog11 and ADAS-Cog13
* Verbal Fluency Task
* Coding
* FAQ
* ADCS-ADL total score and instrumental score
Protocol version 4: change of endpoint timelines to week 116.
Background summary
Gantenerumab (or RO4909832) is a fully human anti Amyloid beta (Ab) peptide
antibody developed by in vitro selection utilizing aggregated Ab and in vitro
maturation within a complete human Ig, subclass-1 framework (IgG1).
Gantenerumab recognizes a conformational epitope
of Ab present in aggregated Ab and that is demonstrated for both major species
of Ab that is, Ab*1*40 and Ab 1*42. Gantenerumab has a molecular mass of 146.3
kDa. In vitro, gantenerumab recognizes synthetic aggregated Ab fibrils and Ab
oligomers with high nanomolar affinity. Based on additional in vitro studies
and studies in animal models, the pharmacologic profile suggests that in humans
gantenerumab may prevent, inhibit, and reduce accumulation of Ab, which is
believed to play an important role in the pathogenesis of AD.
Study objective
This study will evaluate the efficacy and safety of gantenerumab compared with
placebo in patients with early (prodromal to mild) Alzheimer's disease (AD).
Study design
This is a Phase III, multicenter, randomized, double-blind, placebo-controlled,
parallel-group study designed to evaluate the efficacy and safety of
gantenerumab in patients with early (prodromal to mild) AD. The planned number
of patients for the global enrollment phase for the study is approximately 760
patients: randomized in a 1:1 ratio to receive gantenerumab and placebo (380
patients randomized to gantenerumab and 380 randomized to placebo). For more
information, see section 16 of the study protocol.
Protocol version 4: increase of included participants of 1016
Intervention
Gantenerumab (target dose 510 mg) or placebo will be administered by SC
injection to all patients.
Study burden and risks
SIDE EFFECTS KNOWN TO BE ASSOCIATED WITH GANTENERUMAB
As of 31 May 2019, approximately 1400 patients have been exposed to
gantenerumab. Gantenerumab is still being studied, and the side effects
associated with this treatment are not completely known yet. The most frequent
risks associated with gantenerumab, which have been identified to date, are
effects on brain and injection-site reactions as described below.
EFFECTS ON THE BRAIN
Some patients who received gantenerumab or other investigational drugs similar
to gantenerumab had some changes in their MRI brain scans. These may include
swelling. Other changes include something called *microbleeds,* which are very
small areas in the brain where a nearby blood vessel may have leaked.
Microbleeds can occur spontaneously and are sometimes seen in people who did
not receive gantenerumab or similar drugs. These MRI changes occurred more
frequently in people who have a certain type of *APOE* gene.
In previous and ongoing studies, approximatively 1400 patients have received
gantenerumab on doses ranging from 105-1200 mg. In some of these patients, MRI
changes compatible with brain swelling were observed. Swelling was also
observed in very few patients who received placebo. The vast majority of
patients reported no symptoms at the time of brain swelling and the swelling
resolved spontaneously when the study drug was withheld. In few cases,
patients developed symptoms, which were mostly of mild intensity (for example,
headache) and sometimes serious (for example, confusion or seizure/epilepsy).
Overall, such events did not occur more frequently than expected in the AD
population; however, it cannot be excluded that the presence of brain swelling
contributed to or triggered the onset of the symptoms.
INJECTION-SITE REACTIONS
Gantenerumab may cause a reaction when given as a subcutaneous (under the skin)
injection. To date, the most common events occurring more frequently with
gantenerumab than with placebo were local injection reactions such as reddening
of the skin at the site of injection. Most of these events were of mild
intensity and resolved without treatment.
TO DATE, THERE HAVE BEEN NO REPORTS OF SERIOUS ALLERGIC REACTIONS TO
GANTENERUMAB.
For other risks please see paragraph 5 of the main ICF and safety setions in
the protocol.
Beneluxlaan 2a Beneluxlaan 2a
3446 GR Woerden 3446 GR Woerden
NL
Beneluxlaan 2a Beneluxlaan 2a
3446 GR Woerden 3446 GR Woerden
NL
Listed location countries
Age
Inclusion criteria
- Age 50-90 years
- Meets National Institute on Aging/Alzheimer's Association (NIAAA) core
clinical criteria for probable AD dementia or prodromal AD (consistent with the
NIAAA diagnostic criteria and guidelines for mild cognitive impairment)
- Evidence of AD pathological process, as confirmed by cerebrospinal fluid
or amyloid positron emission tomography scan
- Demonstrate abnormal memory function
- MMSE score between 22-30 (inclusive)
- Clinical Dementia Rating Global Score of 0.5 or 1.0
- Availability of a reliable study partner who accepts to participate in
study procedure throughout the study duration
- If receiving symptomatic AD medication the dosing regimen must have been
stable for 3 months prior to screening
Exclusion criteria
- Any evidence of a condition other than AD that may affect cognition
- History or presence of clinically evident systemic vascular disease that
in the opinion of the investigator has the potential to affect cognitive
function
- History of schizophrenia, schizoaffective disorder, major depression, or
bipolar disorder
- Unstable or clinically significant cardiovascular, kidney or liver disease
- At risk of suicide in the opinion of the investigator
- Alcohol or substance abuse in past 2 years
- Relevant brain hemorrhage, bleeding disorder and cerebrovascular
abnormalities
- Any contraindications to brain magnetic resonance imaging
- Uncontrolled hypertension
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001365-24-NL |
| ClinicalTrials.gov | NCT03443973 |
| CCMO | NL65034.100.18 |