A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (GS2)

Novartis

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Alzheimers Disease

Treatments: Drug: CNP520 50mg; Other: Matching placebo; Drug: CNP520 15mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03131453

2016-002976-28 (EudraCT Number)

CCNP520A2202J

Details and patient eligibility

About

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.

Full description

This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired participants aged 60 to 75 years, with at least one apolipoprotein E allele (APOE4), (homozygotes (HMs) or heterozygotes (HTs)) and, if HTs, with evidence of elevated brain amyloid. The participants were randomized to either CNP520 50 mg, CNP520 15 mg or placebo a 2:1:2 ratio and was stratified based on amyloid status. The planned treatment period of 5 to 8 years was not achieved due to early study termination.

Enrollment: 1,145 patients

Sex: All

Ages: 60 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,145 participants in 3 patient groups, including a placebo group

CNP520 50 mg

Experimental group

Description:

50 mg capsule taken orally once daily

Treatment:

Drug: CNP520 50mg

CNP520 15 mg

Experimental group

Description:

15 mg capsule taken orally once daily

Treatment:

Drug: CNP520 15mg

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Matching placebo