Alzheimer's DiseasePhase 2REALNCT01075763
A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease
A Phase 2 study testing Interferon beta-1a in people with Alzheimer's Disease, run by Merck KGaA, Darmstadt, Germany at 1 site in Italy.
Trial summary
This was a 52-week, multicentric, phase II, pilot study conducted in 40 subjects with early-onset Alzheimer's disease (AD) to evaluate safety, tolerability and clinical efficacy of subcutaneous (sc) interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] in the treatment of AD by comparing the… Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Interferon beta-1a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2004to May 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects aged between 50 and 75 years
- Subjects diagnosed with AD, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
- Subjects with MMSE score of 20 to 26 (inclusive)
- Subjects supervised by a caregiver
- Subjects who have been given informed written consent and approval of the Local Ethical Committee
Who cannot join
- Subjects with constant use in the 3 months prior study enrolment of other drugs that can modify the course of the disease (e.g. statins, nonsteroidal anti-inflammatory drugs [NSAIDs] and steroids) or symptomatic cognitive treatments (e.g. cholinesterase inhibitors)
- Subjects with modified Hachinski Ischemic Score ≥ 4
- Subjects who are unable to undergo neuropsychological evaluation (including analphabetism)
- Subjects with significant liver (aspartate aminotransferase, alanine aminotransferase , alkaline phosphatase > 2.0 times the upper limit of normal [ULN] of the local laboratory, or total bilirubin > 1.5 times the ULN of the local laboratory), thyroid (according to clinical judgment) or hematological dysfunctions (e.g. leucocytes ≤ 2.0 * 109/Liter [L]; platelets ≤ 100 * 109/L; hemoglobin ≤ 12 gram/deciliter [g/dL] for women and ≤ 13 g/dL for men, serum albumin ≤ 3 g/dL)
- Subjects with history (past or recurrent) of depression unresponsive to medication or past medical history of suicidal ideation
- Subjects with severe cardiac disease (angina, congestive heart failure class 3-4 New York Heart Association [NYHA] Functional Classification , or severe arrhythmia)
Show all 9Show fewer
- Subjects with epilepsy
- Subjects with concomitant use of hypnotic, anxiolytic, antidepressant, antipsychotic, anticholinergic
- Subjects with known allergic reactions against IFNs or other components of the applied drug
Trial locations and contacts
1 site in 1 country.
Italy1 site
U.VA. Neurologia - Azienda Ospedaliera Garibaldi Nesina
Catania, CT, 95122
About this study
Official title: Pilot Trial of Interferon Beta-1a in Alzheimer's Disease
This was a 52-week, multicentric, phase II, pilot study conducted in 40 subjects with early-onset Alzheimer's disease (AD) to evaluate safety, tolerability and clinical efficacy of subcutaneous (sc) interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] in the treatment of AD by comparing the neuropsychological performance changes into placebo and treatment arms from screening/baseline to 52 week.
Read the detailed description
Alzheimer's disease is characterized by progressive cognitive impairment resulting from neuronal loss. The primary pathological feature of the disease is the extracellular deposition of fibrillary amyloid and its compaction into senile plaques. The senile plaque is the focus of a complex cellular reaction involving the activation of both microglia and astrocytes adjacent to the amyloid plaque. In fact, microglias are the most abundant and prominent cellular components associated with these plaques. Plaque-associated microglia exhibits a reactive or activated phenotype. Through the acquisition of a reactive phenotype, microglia responds to various stimuli, as is evident by the increased expression of numerous cell-surface molecules, including major histocompatibility complex (MHC) class-II antigens and complement receptors.
Traditionally, multiple sclerosis (MS) has been considered a "demyelinating" disease. Recent immunocytochemical studies suggest that MS may be more than a demyelinating disorder, and that even in early stages of the disease, MS pathological scenario envisages axonal damage. Interferons, the modern therapeutic strategies for the treatment of MS, are cytokines - proteins which lead to a network of signals within different cells. In the immune system, IFNs act at different levels. For example, IFNs increase the expression of MHC class II antigens and, thereby, facilitate the antigen-presenting process and the activation of lymphocytes. T-lymphocytes are important targets of IFN immunomodulation. In MS, it is believed that IFN beta suppresses the production of proinflammatory cytokines such as IFN-γ and TNF-α, and increases the production of immunosuppressive cytokines such as interleukin-4 (IL-4) and IL-10. Since the activation of microglia and astrocytes is common to both AD and MS, IFN beta could have therapeutic applications in the treatment of AD. Furthermore, recent studies have also found that through astrocyte production, IFNs promote the activation of nerve-growth factor.
OBJECTIVES
- To evaluate safety, tolerability and clinical efficacy of IFN beta-1a (Rebif® 22 mcg, tiw) in the treatment of AD
In this study, subjects were randomized into two groups: the first group (treatment arm, n=20) received Rebif® 22 mcg tiw; the second group (placebo arm, n=20) received placebo. The treatment period was for 28 weeks and subjects were followed up to Week 52. Efficacy was determined by comparing neuropsychological performance changes into placebo and treatment arms from screening/baseline to Week 52.
On Day 1 of the study treatment period, subjects received injection training and were administered the first dose of Rebif under the supervision of the clinical personnel by subcutaneous injection tiw at approximately the same time each day preferably in the late afternoon or evening. All subjects received 28 weeks of therapy and after 24 weeks from the therapy conclusion, a termination visit was conducted.
- Conditions
- Alzheimer's Disease
- Being tested
- Interferon beta-1a, Placebo
- Keywords
- Alzheimer's, Dementia, Interferon beta-1a, Rebif
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon beta-1aDrug
Also called Rebif®
Interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] administered subcutaneously (sc)
PlaceboDrug
The inactive substance (placebo) looks the same as Interferon beta-1a (Rebif®), and is given the same way
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm - Rebif® | Experimental | Subjets in this arm received interferon beta-1a (Rebif® 22 mcg tiw) Receives: Drug: Interferon beta-1a |
| Placebo arm | Placebo comparator | Subjects in this arm received placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit).
Measured: Baseline and Week 52
Secondary outcomes (8)
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit).
Measured: Week 12 and 28
Mini Mental Status Examination (MMSE) Score
MMSE is a tool for screening cognitive decline associated with dementia. It is a brief examination intended to evaluate an adult participant's level of cognitive functioning. The test is performed in following areas: orientation in time and place, learning and immediate recall, mental control and concentration, short-term recall, naming ability, language expression, verbal comprehension, writing comprehension, writing ability and visual-spatial coordination. Scores range between 0 (maximum cognitive deficit) and 30 (no cognitive deficit).
Measured: Baseline, Week 12, 28 and 52
Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score
ADAS-NonCog is a subscale of ADAS aimed to evaluate the non-cognitive features such as mood state and behavioral changes. It takes about 10 minutes to be performed and includes 10 items: testing tearful, depressed mood, concentration/distractibility, uncooperative to testing, delusions, hallucinations, pacing, motor activity increase, tremors and appetite change. Scores range between 0 (excellent performance) and 35 (worst performance).
Measured: Baseline, Week 12, 28 and 52
Instrumental Activities of Daily Living (IADL) Score
IADL is used to evaluate participants with early-stage disease, both to assess level of disease and to determine participant's ability of self-care. IADL scale measures functional impact of emotional, cognitive, and physical impairments. It provides information about participants' compromising rate and care he might need. It includes 8 items: testing ability to use telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication and ability to handle finances. Scores range between 0 (impairment) and 8 (full independence).
Measured: Baseline, Week 28 and 52
Physical Self-Maintenance Scale (PSMS) Score
PSMS designed as a disability measure for use in planning and evaluating treatment in elderly participants living in community or in institutions, is Guttman scale containing 6 items of self-care. The scale is based on theory that human behavior can be ordered in a hierarchy of complexity, within each category, a further hierarchy of complexity runs from basic to complex activities. It includes 6 items, testing the following areas: toilet use, eating, dressing, physical appearance, deambulation and bath. Scores range between 0 (excellent performance) and 30 (worst performance).
Measured: Baseline, Week 28 and 52
Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score
CIBIC-PLUS: structured instrument based on comprehensive evaluation of 3 domains: participant cognition, behavior and functioning, including assessment of daily living activities. It includes 15 items and represents assessment of skilled clinician using validated scales based on the observation at interviews conducted separately with participant and caregiver familiar with behavior of participant. According to comparison between baseline and follow-up assessments, scores can range between 1 (markedly improved) and 7 (markedly worsened), with 4 indicating no change observed between two visits.
Measured: Week 28 and 52
Geriatric Depression Scale (GDS) Score
The GDS consists of 30 'yes' or 'no' items aimed to assess depression. One point is assigned to each answer and the cumulative score is rated on a scoring grid. Scores are grouped as follows: 0-9 'normal', 10-19 'mildly depressed', and 20-30 'severely depressed'.
Measured: Baseline, Week 28 and 52
Global Deterioration Scale Score
Global deterioration scale includes seven different diagnostic stages ranging between "no cognitive deterioration" and "very serious cognitive deterioration". It investigates the cognitive impairment. Scores range between 1 (no cognitive deterioration) and 7 (very severe cognitive decline).
Measured: Baseline, Week 28 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2010 (estimated)
- Study startNov 2004
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.P.A., Italy
- Responsible party
- Sponsor
- Investigators
- Andrea Paolillo, MD, PhD, Study director, Merck Serono S.P.A., Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01075763
- Sponsor's protocol ID
- 24386
- Acronym
- REAL
- Status last verified
- Jan 2014
- First submitted
- 24 Feb 2010
- Last updated
- 13 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial of Interferon Beta-1a in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01075763
- Acronym / sponsor ID
- REAL / 24386
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's, Dementia, Interferon beta-1a, Rebif
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.P.A., Italy
- Study start
- Nov 2004
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 25 Feb 2010 (estimated)
- Results
- Posted 4 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a 52-week, multicentric, phase II, pilot study conducted in 40 subjects with early-onset Alzheimer's disease (AD) to evaluate safety, tolerability and clinical efficacy of subcutaneous (sc) interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] in the treatment of AD by comparing the neuropsychological performance changes into placebo and treatment arms from screening/baseline to 52 week.
Detailed description
Alzheimer's disease is characterized by progressive cognitive impairment resulting from neuronal loss. The primary pathological feature of the disease is the extracellular deposition of fibrillary amyloid and its compaction into senile plaques. The senile plaque is the focus of a complex cellular reaction involving the activation of both microglia and astrocytes adjacent to the amyloid plaque. In fact, microglias are the most abundant and prominent cellular components associated with these plaques. Plaque-associated microglia exhibits a reactive or activated phenotype. Through the acquisition of a reactive phenotype, microglia responds to various stimuli, as is evident by the increased expression of numerous cell-surface molecules, including major histocompatibility complex (MHC) class-II antigens and complement receptors.
Traditionally, multiple sclerosis (MS) has been considered a "demyelinating" disease. Recent immunocytochemical studies suggest that MS may be more than a demyelinating disorder, and that even in early stages of the disease, MS pathological scenario envisages axonal damage. Interferons, the modern therapeutic strategies for the treatment of MS, are cytokines - proteins which lead to a network of signals within different cells. In the immune system, IFNs act at different levels. For example, IFNs increase the expression of MHC class II antigens and, thereby, facilitate the antigen-presenting process and the activation of lymphocytes. T-lymphocytes are important targets of IFN immunomodulation. In MS, it is believed that IFN beta suppresses the production of proinflammatory cytokines such as IFN-γ and TNF-α, and increases the production of immunosuppressive cytokines such as interleukin-4 (IL-4) and IL-10. Since the activation of microglia and astrocytes is common to both AD and MS, IFN beta could have therapeutic applications in the treatment of AD. Furthermore, recent studies have also found that through astrocyte production, IFNs promote the activation of nerve-growth factor.
OBJECTIVES
- To evaluate safety, tolerability and clinical efficacy of IFN beta-1a (Rebif® 22 mcg, tiw) in the treatment of AD
In this study, subjects were randomized into two groups: the first group (treatment arm, n=20) received Rebif® 22 mcg tiw; the second group (placebo arm, n=20) received placebo. The treatment period was for 28 weeks and subjects were followed up to Week 52. Efficacy was determined by comparing neuropsychological performance changes into placebo and treatment arms from screening/baseline to Week 52.
On Day 1 of the study treatment period, subjects received injection training and were administered the first dose of Rebif under the supervision of the clinical personnel by subcutaneous injection tiw at approximately the same time each day preferably in the late afternoon or evening. All subjects received 28 weeks of therapy and after 24 weeks from the therapy conclusion, a termination visit was conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment arm - Rebif® | Experimental | Drug: Interferon beta-1aSubjets in this arm received interferon beta-1a (Rebif® 22 mcg tiw) |
| Placebo arm | Placebo comparator | Drug: PlaceboSubjects in this arm received placebo |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects aged between 50 and 75 years
- Subjects diagnosed with AD, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
- Subjects with MMSE score of 20 to 26 (inclusive)
- Subjects supervised by a caregiver
- Subjects who have been given informed written consent and approval of the Local Ethical Committee
Key exclusion criteria (9 listed)
- Subjects with constant use in the 3 months prior study enrolment of other drugs that can modify the course of the disease (e.g. statins, nonsteroidal anti-inflammatory drugs [NSAIDs] and steroids) or symptomatic cognitive treatments (e.g. cholinesterase inhibitors)
- Subjects with modified Hachinski Ischemic Score ≥ 4
- Subjects who are unable to undergo neuropsychological evaluation (including analphabetism)
- Subjects with significant liver (aspartate aminotransferase, alanine aminotransferase , alkaline phosphatase > 2.0 times the upper limit of normal [ULN] of the local laboratory, or total bilirubin > 1.5 times the ULN of the local laboratory), thyroid (according to clinical judgment) or hematological dysfunctions (e.g. leucocytes ≤ 2.0 * 109/Liter [L]; platelets ≤ 100 * 109/L; hemoglobin ≤ 12 gram/deciliter [g/dL] for women and ≤ 13 g/dL for men, serum albumin ≤ 3 g/dL)
- Subjects with history (past or recurrent) of depression unresponsive to medication or past medical history of suicidal ideation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon beta-1aAlso: Rebif®Interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] administered subcutaneously (sc) | Drug | Treatment arm - Rebif® |
| PlaceboThe inactive substance (placebo) looks the same as Interferon beta-1a (Rebif®), and is given the same way | Drug | Placebo arm |
Primary outcome
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
Time frame: Baseline and Week 52
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit).
8 secondary outcomes
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
Time frame: Week 12 and 28
Mini Mental Status Examination (MMSE) Score
Time frame: Baseline, Week 12, 28 and 52
Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score
Time frame: Baseline, Week 12, 28 and 52
Instrumental Activities of Daily Living (IADL) Score
Time frame: Baseline, Week 28 and 52
Physical Self-Maintenance Scale (PSMS) Score
Time frame: Baseline, Week 28 and 52
Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score
Time frame: Week 28 and 52
Geriatric Depression Scale (GDS) Score
Time frame: Baseline, Week 28 and 52
Global Deterioration Scale Score
Time frame: Baseline, Week 28 and 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Paolillo, MD, PhD study director
Merck Serono S.P.A., Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interferon beta-1a in people with Alzheimer's Disease, run by Merck KGaA, Darmstadt, Germany at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score (time frame: Baseline and Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2014.