A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease

NCT03131453 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCNP520A2202J2016-002976-28
• Study Type: interventional
• Target: 1,145
• Locations: 25 countries
• Sites: 194

Brief Summary

The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.

Conditions

Alzheimers Disease

Keywords

Placebo controlled; APOE4 carriers; Homozygotes; Heterozygotes; Brain Amyloid; Aβ lowering; BACE-1 inhibitor; CNP520; elderly; preclinical Alzheimers disease; Alzheimers Disease; Prevention; Unimpaired cognition

Outcome Measures

Primary Outcomes (2)

• Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))

  Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.

  Baseline to last cognitive assessment performed (up to day 648)

• Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score

  APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.

  Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)

Secondary Outcomes (13)

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score

  Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)

• Change in the Total and Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)

• Change in the Everyday Cognition Scale (ECog-Subject) Total Scores

  Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)

• Change in the Everyday Cognition Scale (ECog-Informant) Total Scores

  Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)

• Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)

  Baseline up to study termination approximately 617 days

Study Arms (3)

CNP520 50 mg

EXPERIMENTAL

50 mg capsule taken orally once daily

Drug: CNP520 50mg

CNP520 15 mg

EXPERIMENTAL

15 mg capsule taken orally once daily

Drug: CNP520 15mg

Placebo

PLACEBO COMPARATOR

Matching placebo to 15 and 50 mg CNP520 taken orally once daily

Other: Matching placebo

Interventions

CNP520 50mg DRUG

50 mg capsule

CNP520 50 mg

CNP520 15mg DRUG

15 mg capsule

CNP520 15 mg

Matching placebo OTHER

Matching placebo for 15 and 50 mg capsules

Placebo

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.
• Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential
• Cognitively unimpaired as evaluated by memory tests performed at screening.
• Participant's willingness to have a study partner.
• Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).

You may not qualify if:

• Any disability that could have prevented the participants from completing all study requirements. -
• Current medical or neurological condition that could have impacted cognition or performance on cognitive assessments.
• Advanced, severe progressive or unstable disease that could have interfered with the safety, tolerability and study assessments, or put the participant at special risk.
• History of malignancy of any organ system, treated or untreated, within the past 60 months.
• Indication for, or current treatment with ChEIs and/or another AD treatment (e.g. memantine).
• Contraindication or intolerance to MRI.
• Brain MRI results showing findings unrelated to AD that, in the opinion of the Investigator might be a leading cause to future cognitive decline, could have posed a risk to the participant, or could have prevented a satisfactory MRI assessment for safety monitoring.
• Suicidal Ideation in the past six months, or Suicidal Behavior in the past two years.
• A positive drug screen at Screening, if, in the Investigator's opinion, was is due to drug abuse.
• Significantly abnormal laboratory results at Screening, not as a result of a temporary condition.
• Current clinically significant ECG findings.
• Clinically relevant depigmenting or hypopigmenting conditions (e.g. albinism, vitiligo) or active / history of chronic urticaria in the past year.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Amgen: collaborator
• Banner Alzheimer's Institute: collaborator

Study Sites (194)

Banner Alzheimer's Institute, 901 East Willetta Street

Phoenix, Arizona, 85006, United States

Location

Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Building B

Sun City, Arizona, 85351, United States

Location

Novartis Investigative Site

Tucson, Arizona, 85724, United States

Location

ATP Clinical Research Inc, 3151 Airway Avenue T 3

Costa Mesa, California, 92626, United States

Location

Irvine Center for Clinical Res, 2515 McCabe Way

Irvine, California, 92618, United States

Location

Torrance Clinical Research Institute, 25043 Narbonne Avenue

Lomita, California, 90717, United States

Location

Novartis Investigative Site

Oxnard, California, 93030, United States

Location

Novartis Investigative Site

Palo Alto, California, 94304, United States

Location

Novartis Investigative Site

San Diego, California, 92103, United States

Location

Syrentis Clinical Research, 1401 N Tustin Ave, Suite 130

Santa Ana, California, 92705, United States

Location

Novartis Investigative Site

Sebastopol, California, 95472, United States

Location

Novartis Investigative Site

Sherman Oaks, California, 91403, United States

Location

Mountain Neurological Research, 350 Market Street, Suite 316

Basalt, Colorado, 81621, United States

Location

Colorado Springs Neurological, 2312 North Nevada Avenue, Suite 100

Colorado Springs, Colorado, 80907, United States

Location

Denver Neurological Clinic, 950 E Harvard Ave

Denver, Colorado, 80210, United States

Location

Yale University, One Church Street, Suite 600

New Haven, Connecticut, 06519, United States

Location

Novartis Investigative Site

Stamford, Connecticut, 06905, United States

Location

Novartis Investigative Site

Washington D.C., District of Columbia, 20057, United States

Location

Novartis Investigative Site

Atlantis, Florida, 33462-6608, United States

Location

Quantum Laboratories

Deerfield Beach, Florida, 33064, United States

Location

Brain Matters Research, Inc., 800 NW 17th Avenue

Delray Beach, Florida, 33445, United States

Location

Infinity Clinical Research LLC, 4925 Sheridan Street, Suite 200

Hollywood, Florida, 33021, United States

Location

Alzheimer's Research and Treatment Center, 5065 State Road 7, Suite 102

Lake Worth, Florida, 33449, United States

Location

Meridien Research, 2300 Maitland center, Pkwy Ste 230

Maitland, Florida, 32751, United States

Location

Novartis Investigative Site

Melbourne, Florida, 32940, United States

Location

Novartis Investigative Site

Merritt Island, Florida, 32952, United States

Location

Novartis Investigative Site

Miami, Florida, 33032, United States

Location

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

New Horizon Research Center, 11880 SW 40 St., Suite 405

Miami, Florida, 33175, United States

Location

Miami-Dade Medical Research, 8955 SW 87 CT, Suite 112

Miami, Florida, 33176, United States

Location

Novartis Investigative Site

Miami Beach, Florida, 33140, United States

Location

Compass Research, LLC,100 West Gore Street, Suite 202

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Ormond Beach, Florida, 32174, United States

Location

Novartis Investigative Site

Palm Beach Gardens, Florida, 33410, United States

Location

Novartis Investigative Site

Port Orange, Florida, 32127, United States

Location

Roskamp Institute, Inc., 2040 Whitfield Avenue

Sarasota, Florida, 34243, United States

Location

Novartis Investigative Site

Tallahassee, Florida, 32308, United States

Location

Novartis Investigative Site

Tampa, Florida, 33613, United States

Location

Novartis Investigative Site

West Palm Beach, Florida, 33407, United States

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Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Novartis Investigative Site

Columbus, Georgia, 31909, United States

Location

Novartis Investigative Site

Decatur, Georgia, 30033, United States

Location

Hawaii Pacific Neuroscience, 2230 Liliha st 104

Honolulu, Hawaii, 96817, United States

Location

Advanced Clinical Research, 2950 E Magic View Dr, Suite 182

Meridian, Idaho, 83642, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60640, United States

Location

Alexian Brothers Neuroscience, 800 Biesterfield Rd, Neuroscience Institute Brock

Elk Grove Village, Illinois, 60007, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Novartis Investigative Site

Fairway, Kansas, 66205, United States

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Novartis Investigative Site

Wichita, Kansas, 67206, United States

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Novartis Investigative Site

Wichita, Kansas, 67214, United States

Location

Novartis Investigative Site

Lexington, Kentucky, 40536-0284, United States

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Novartis Investigative Site

Bangor, Maine, 04401, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02118, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02215, United States

Location

QUEST Research Institute, 28595 Orchard Lake Road, Suite 301

Farmington Hills, Michigan, 48334, United States

Location

Novartis Investigative Site

Kalamazoo, Michigan, 49008, United States

Location

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Hattiesburg Clinic, 415 South 28th Avenue

Hattiesburg, Mississippi, 39401, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63104, United States

Location

Novartis Investigative Site

Omaha, Nebraska, 68198 7680, United States

Location

Novartis Investigative Site

West Long Branch, New Jersey, 07764, United States

Location

Albuquerque Neuroscience, 101 Hospital Loop ne, 209 209

Albuquerque, New Mexico, 87109, United States

Location

Novartis Investigative Site

Brooklyn, New York, 11235, United States

Location

Novartis Investigative Site

East Syracuse, New York, 13057, United States

Location

Novartis Investigative Site

Latham, New York, 12110, United States

Location

NYU Langone Medical Center, 145 East 32nd Street, 2nd Floor, Room 226

New York, New York, 10016, United States

Location

Novartis Investigative Site

Orangeburg, New York, 10962, United States

Location

Novartis Investigative Site

Rochester, New York, 14642, United States

Location

ANI Neurology, PLLC dba Alzhe, 7809 Sardis Road

Charlotte, North Carolina, 28270, United States

Location

Novartis Investigative Site

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Greensboro, North Carolina, 27410, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45242, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Tulsa Clinical Research LLC, 1705 E 19th ST., STE 406/408

Tulsa, Oklahoma, 74104, United States

Location

Summit Research Network, 2701 NW Vaughn St, Suite 350

Portland, Oregon, 97210, United States

Location

Novartis Investigative Site

Portland, Oregon, 97239, United States

Location

Novartis Investigative Site

Jenkintown, Pennsylvania, 19046, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Abington Neurological Associate Ltd., 2325 Maryland Road, Suite 100

Willow Grove, Pennsylvania, 19090, United States

Location

Rhode Island Hospital and Memory Research Institute, 1018 Waterman Ave

East Providence, Rhode Island, 02914, United States

Location

Butler Hospital, 345 Blackstone Blvd.

Providence, Rhode Island, 02906, United States

Location

Roper Hospital, 316 Calhoun Street 5th Floor

Charleston, South Carolina, 29401, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

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Novartis Investigative Site

Memphis, Tennessee, 38119, United States

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Novartis Investigative Site

Nashville, Tennessee, 37212, United States

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Novartis Investigative Site

Austin, Texas, 78757, United States

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Novartis Investigative Site

Dallas, Texas, 75231, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Houston, Texas, 77054, United States

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Novartis Investigative Site

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Bennington, Vermont, 05201, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1428AQK, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1012AAR, Argentina

Location

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

Location

Novartis Investigative Site

Heidelberg West, Victoria, 3081, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Kelowna, British Columbia, V1Y1Z9, Canada

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Novartis Investigative Site

Kentville, Nova Scota, B4N 4K9, Canada

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Novartis Investigative Site

Halifax, Nova Scotia, B3S 1M7, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1G 1Z3, Canada

Location

Toronto Memory Program, 1 Valleybrook Drive Suite 400

Toronto, Ontario, M3B 2S7, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M4G 3E8, Canada

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Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

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Novartis Investigative Site

Gatineau, Quebec, J8T 8J1, Canada

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Novartis Investigative Site

Greenfield Park, Quebec, J4V 2J2, Canada

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Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

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Novartis Investigative Site

Santiago, 7500710, Chile

Location

Novartis Investigative Site

Santiago, 838 0456, Chile

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200080, China

Location

Novartis Investigative Site

Beijing, 100053, China

Location

Novartis Investigative Site

Guangdong, 510370, China

Location

Novartis Investigative Site

Kuopio, 70210, Finland

Location

Novartis Investigative Site

Turku, 20520, Finland

Location

Novartis Investigative Site

Strasbourg, Cedex, 67098, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Paris, 75651, France

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Novartis Investigative Site

Rouen, 76031, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Villeurbanne, 69100, France

Location

Novartis Investigative Site

Bayreuth, 95445, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Cologne, 50937, Germany

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Novartis Investigative Site

Leipzig, 04107, Germany

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Novartis Investigative Site

Mannheim, 68159, Germany

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Novartis Investigative Site

Siegen, 57076, Germany

Location

Novartis Investigative Site

Kopavogur, IS-201, Iceland

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Novartis Investigative Site

Ashkelon, 78278, Israel

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Novartis Investigative Site

Haifa, 31096, Israel

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Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Brescia, BS, 25100, Italy

Location

Novartis Investigative Site

Rome, Lazio, 00168, Italy

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

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Novartis Investigative Site

Milan, 20112, Italy

Location

Novartis Investigative Site

Tōon, Ehime, 791-0295, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 814 0180, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 236-0004, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565 0871, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113 8655, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8431, Japan

Location

Novartis Investigative Site

Kodaira, Tokyo, 187-8551, Japan

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Novartis Investigative Site

Shinjuku-ku, Tokyo, 160 8582, Japan

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Novartis Investigative Site

Chiba, 260 8677, Japan

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Novartis Investigative Site

Osaka, 545-8586, Japan

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Novartis Investigative Site

Mexico City, Mexico CP, 14080, Mexico

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Novartis Investigative Site

Monterrey, Nuevo León, 64710, Mexico

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Novartis Investigative Site

Culiacán, Sinaloa, 80020, Mexico

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Novartis Investigative Site

's-Hertogenbosch, North Brabant, 5223 LA, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1081 GN, Netherlands

Location

Novartis Investigative Site

Torres Vedras, Lisbon District, 2560-280, Portugal

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Novartis Investigative Site

Coimbra, 3000 075, Portugal

Location

Novartis Investigative Site

Lisbon, 1998-018, Portugal

Location

Novartis Investigative Site

Matosinhos Municipality, 4454 513, Portugal

Location

Inspira Clinical Research, Ave Hostos 405

San Juan, 00918, Puerto Rico

Location

Novartis Investigative Site

Singapore, 308433, Singapore

Location

Novartis Investigative Site

Rosebank, Johannesburg, 2132, South Africa

Location

Novartis Investigative Site

Cape Town, Western Cape, 7530, South Africa

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Novartis Investigative Site

George, ZAF, 6529, South Africa

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Novartis Investigative Site

Suwon, Gyeonggi-do, 16499, South Korea

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Novartis Investigative Site

Busan, 49201, South Korea

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Novartis Investigative Site

Incheon, 22332, South Korea

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Novartis Investigative Site

Seoul, 05505, South Korea

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Novartis Investigative Site

Seoul, 06351, South Korea

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Novartis Investigative Site

Terrassa, Barcelona, 08221, Spain

Location

Novartis Investigative Site

Pozuelo de Alarcón, Madrid, 28223, Spain

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Novartis Investigative Site

Barcelona, 08005, Spain

Location

Novartis Investigative Site

Barcelona, 08014, Spain

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Novartis Investigative Site

Donostia / San Sebastian, 20009, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Basel, CH, 4002, Switzerland

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Novartis Investigative Site

Geneva, 1227, Switzerland

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Novartis Investigative Site

Lausanne, CH-1011, Switzerland

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Novartis Investigative Site

Kaoshiung, 83301, Taiwan

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Novartis Investigative Site

New Taipei City, 23561, Taiwan

Location

Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Exeter, Devon, EX2 5DW, United Kingdom

Location

Novartis Investigative Site

Plymouth, Devon, PL6 8BT, United Kingdom

Location

Novartis Investigative Site

London, GBR, W12 7RH, United Kingdom

Location

Novartis Investigative Site

Guildford, Surrey, GU27YD, United Kingdom

Location

Novartis Investigative Site

Avon, BA1 3NG, United Kingdom

Location

Novartis Investigative Site

Birmingham, B16 8QQ, United Kingdom

Location

Novartis Investigative Site

Bristol, BS10 5NB, United Kingdom

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Novartis Investigative Site

Dundee, DD1 9SY, United Kingdom

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Novartis Investigative Site

Glasgow, United Kingdom

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Novartis Investigative Site

London, W12 0HS, United Kingdom

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Novartis Investigative Site

London, W1G 9JF, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Umibecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The study was terminated due to safety issues.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2017
• First Posted: April 27, 2017
• Study Start: August 3, 2017
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (7); AU (3); ME (3); BE (2); CA (10); IC (1); SG (1); CL (2); FR (6); IL (5); IT (4); DE (6); PR (1); US (95); AR (2); PT (4); NL (2); ZA (3); CH (3); CN (3); FI (2); JP (10); KR (5); TW (3); GB (11)