A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (GS1)

Novartis

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Alzheimers Disease

Treatments: Other: Alum; Other: Placebo to CAD106; Other: Placebo to CNP520; Biological: CAD106 Immunotherapy; Drug: CNP520

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02565511

2015-002715-15 (EudraCT Number)

1UF1AG046150-01 (U.S. NIH Grant/Contract)

CAPI015A2201J

Details and patient eligibility

About

The purpose of this study was to test whether two investigational drugs called CAD106 and CNP520, administered separately, could slow down the onset and progression of clinical symptoms associated with Alzheimer's disease (AD) in participants at the risk to develop clinical symptoms based on their age and genotype.

Full description

The study (also known as the Generation Study 1, GS1) was conducted as part of the Alzheimer's Prevention Initiative (API) program.

This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired APOE4 homozygotes (HMs) aged 60 to 75 years. Participants were enrolled into Cohort I (CAD106) or Cohort II (CNP520).

The planned treatment period of 5 to 8 years was not achieved due to early study termination.

The study was terminated due to unexpected changes in cognitive function, brain volume loss, and body weight loss. Cohort II (CNP520) treatment was stopped and evaluated through an off-treatment follow-up period. After the decision to terminate Cohort II of the study (CNP520), treatment with CAD106 (Cohort I) was also terminated.

Enrollment: 480 patients

Sex: All

Ages: 60 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Consented to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype.
• Male or female, age 60 to 75 years inclusive. Females were to be post-menopausal.
• Mini-Mental State Examination (MMSE) total score ≥ 24 and cognitively unimpaired as evaluated by memory tests
• Homozygous APOE4 genotype.
• Participant willing to have a study partner.

Key Exclusion Criteria:

• Any disability that prevented the participant 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 may 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 60 months prior to screening.
• History of hypersensitivity to any of the investigational drugs or their excipients / adjuvant or to drugs of similar chemical classes.
• Indication or on current treatment with ChEIs and/or another AD treatment (e.g. memantine).
• Contraindication or intolerance to MRI or PET investigations (with fluorinated radio ligands).
• Brain MRI results showing findings unrelated to AD that, in the opinion of the Investigator could have been a leading cause to future cognitive decline, pose a risk to the participant, or prevent a satisfactory MRI assessment for safety monitoring.
• Suicidal Ideation in the past six months or Suicidal Behavior in the past two years, prior to screening.
• A positive drug screen at Screening, if, in the Investigator's opinion, this was due to drug abuse.
• Significantly abnormal laboratory results at Screening, or infection not as a result of a temporary condition.
• Current clinically significant ECG findings. For Cohort - I only: Participants with previous organ transplantation or stem cell transplantation, or indication for treatment with anti-coagulants.

For Cohort - II only: Participants with depigmenting or hypopigmenting conditions (e.g. albinism vitiligo) or active / history of chronic urticarial in the past year.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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480 participants in 4 patient groups, including a placebo group

Cohort I (CAD106)

Experimental group

Description:

CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Treatment:

Biological: CAD106 Immunotherapy

Other: Alum

Cohort I (CAD106 Placebo)

Placebo Comparator group

Description:

Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Treatment:

Other: Alum

Other: Placebo to CAD106

Cohort II (CNP520)

Experimental group

Description:

CNP520 (50 mg) capsules taken orally once daily

Treatment:

Drug: CNP520

Cohort II (CNP520 Placebo)

Placebo Comparator group

Description:

Matching Placebo to CNP520 capsules taken orally once daily

Treatment:

Other: Placebo to CNP520