NCT01821118

A Phase 2, Randomized, Double Blind Placebo Controlled Trial To Evaluate The Safety, Tolerability, Pharmacokinetics And Efficacy Of Pf-04360365 (Ponezumab) In Adult Subjects With Probable Cerebral Amyloid Angiopathy

Completed Phase 2 Results posted Last updated 3 April 2017

What this trial tests

Phase 2 trial testing Ponezumab in Cerebral Amyloid Angiopathy in 36 participants. Completed in 1 September 2015.

Timeline

1 June 2013

Primary endpoint
1 September 2015

1 September 2015

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	36
Start date	1 June 2013
Primary completion	1 September 2015
Estimated completion	1 September 2015
Sites	13 locations across United States, Canada, France, Netherlands, United Kingdom

Drugs / interventions tested

• Ponezumab — full drug profile →
• placebo

Conditions studied

• Cerebral Amyloid Angiopathy — all drugs for Cerebral Amyloid Angiopathy →

Sponsor

Pfizer — full company profile →

Who can join

Adults 55 to 90, any sex, with Cerebral Amyloid Angiopathy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change From Baseline to Day 2 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked Functional Magnetic Resonance Imaging (fMRI)
  Time frame: Baseline, Day 2
  Blood Oxygen Level Dependant (BOLD) fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual corte
• Change From Baseline to Day 90 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked fMRI
  Time frame: Baseline, Day 90
  BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe.

Sponsor's own description

Cerebral Amyloid Angiopathy (CAA) is a condition caused by the build-up of a protein called amyloid, predominantly Aβ40, within the walls of brain blood vessels, especially those blood vessels in the occipital lobe of the brain. Probable CAA may be defined as two or more hemorrhages in the brain cortex in individuals 55 years of age or older. This study will examine the study drug (PF-04360365) vs. placebo (saline) at 10 mg/kg - Day 1 and the maintenance dose of the study drug (PF-04360365) vs. placebo (saline) at 7.5mg/kg on Days 30 and 60. Subjects will be followed for 6 months after receiving the last dose of study medication.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cerebral amyloid angiopathy: emerging concepts.
   Yamada M. · · 2015 · cited 260× · PMID 25692104 · DOI 10.5853/jos.2015.17.1.17
2. Amyloid-beta peptide and tau protein crosstalk in Alzheimer's disease.
   Roda AR, Serra-Mir G, Montoliu-Gaya L, Tiessler L, et al · · 2022 · cited 196× · PMID 35017413 · DOI 10.4103/1673-5374.332127
3. Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease.
   Shinohara M, Murray ME, Frank RD, Shinohara M, et al · · 2016 · cited 99× · PMID 27179972 · DOI 10.1007/s00401-016-1580-y
4. Anti-Aβ Autoantibodies in Amyloid Related Imaging Abnormalities (ARIA): Candidate Biomarker for Immunotherapy in Alzheimer's Disease and Cerebral Amyloid Angiopathy.
   DiFrancesco JC, Longoni M, Piazza F. · · 2015 · cited 61× · PMID 26441825 · DOI 10.3389/fneur.2015.00207
5. Immunotherapy with ponezumab for probable cerebral amyloid angiopathy.
   Leurent C, Goodman JA, Zhang Y, He P, et al · · 2019 · cited 60× · PMID 31020004 · DOI 10.1002/acn3.761
6. Antibody Therapeutics Targeting Aβ and Tau.
   Gallardo G, Holtzman DM. · · 2017 · cited 43× · PMID 28062555 · DOI 10.1101/cshperspect.a024331
7. Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials.
   Nimmo JT, Kelly L, Verma A, Carare RO, et al · · 2021 · cited 31× · PMID 34539340 · DOI 10.3389/fnins.2021.733857
8. Amyloid-beta immunotherapy: the hope for Alzheimer disease?
   Barrera-Ocampo A, Lopera F. · · 2016 · cited 30× · PMID 28293044 · DOI 10.25100/cm.v47i4.2640