An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum

Alzheimer Disease Clinical Trial

Official title:

A Randomized, Two-Period, Double-Blind Placebo-Controlled and Open-Label, Multicenter Extension Study to Determine the Long-Term Safety and Tolerability of JNJ-54861911 in Subjects in the Early Alzheimer's Disease Spectrum

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02406027
• Other study ID #: CR106978
• Secondary ID: 54861911ALZ20042
• Status: Terminated
• Phase: Phase 2
• Start date: July 2, 2015
• Est. completion date: June 28, 2018

Study information

• Verified date: June 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 in participants in the early Alzheimer's disease (AD [progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks]) spectrum that have completed a Phase 1b or Phase 2 clinical trial with JNJ-54861911, who are willing to continue their assigned treatment.

Description:

Participants in the early Alzheimer's Disease (AD) spectrum, enrolled in ongoing or future clinical trials with JNJ-54861911 (Phase 1b or Phase 2 studies) will be provided the opportunity to participate in this study upon completion of their treatment period under the parent protocol. The study will consist of a Screening phase and 2 sequential treatment phases (a 12-month double-blind [DB] treatment phase [placebo controlled] and an open-label [OL] phase [active]) followed by an End-of-Treatment visit. Treatment in OL phase will continue until registration of JNJ-54861911; unless safety issues emerge as determined by the Data Review Committee (DRC) that would warrant termination of the study. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma and CSF pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 90
• Est. completion date: June 28, 2018
• Est. primary completion date: June 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Participants in the early Alzheimer's disease (AD) spectrum at time of enrollment under the parent protocol and according to its inclusion and exclusion criteria, must have very recently completed their treatment in a Phase 1b or Phase 2 JNJ-54861911 clinical study (example [e.g.], 54861911ALZ2002) under the parent protocol. Enrollment in this study should be completed (Day 1 of double-blind [DB] treatment phase) as soon as possible, but within 6 weeks, following completion of their treatment period under the parent protocol. If not defined under the parent protocol, completion of the treatment period is defined as having completed all study related procedures of the last visit of the treatment period under the parent protocol. A screening phase of up to 12 weeks may be allowed following written approval of the Sponsor

• Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol

• Each Participants (or their legally acceptable representative and caregiver depending on disease state and local requirements) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study

• Participants must have a reliable informant (relative, partner, or friend). The informant must be willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or other audio/visual communication). The informant must have sufficient contact such that the Investigator feels he/she can provide meaningful information about the participant's daily function. If possible, an alternate informant meeting these criteria who can replace the primary informant should be identified prior to randomization

Exclusion Criteria:

• Any condition or situation which, in the opinion of the Investigator, may put the participant at significant risk, may confound the study results, or may interfere significantly with participant's participation in the study

• The use of concomitant medications known to prolong the QT/QTc interval

• Participant has a history of moderate or severe hepatic impairment or severe renal insufficiency unless completely resolved for more than a year. Participant has clinically significant ongoing hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric or metabolic conditions (e.g., requiring frequent monitoring or medication adjustments or is otherwise unstable)

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• JNJ-54861911, 10 mg
Participants will self-administer JNJ-54861911 tablet, 10 mg (2*5 mg), orally, once daily.
• JNJ-54861911, 25 mg
Participants will self-administer 1 tablet of JNJ-54861911, containing 25 mg orally, once daily.
• Placebo
Participants will self administer placebo matching to JNJ-54861911 orally once daily.
• JNJ-54861911, 5 mg
Participants will self-administer JNJ-54861911 tablet, 5 mg, orally, once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to 3 years that were absent before treatment or that worsened relative to pre-treatment state. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to 3 years
Secondary	Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels	CSF samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, and ABeta 1-42. ABeta fragments of different length produced by cleavage of amyloid precursor protein (APP) by beta-secretase (BACE) and gamma-secretase complex in brain and excreted into CSF. Participants were classified as asymptomatic at risk: cognitively and functionally normal (Clinical Dementia Rating Scale score [CDR] =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).	Baseline, Double-blind (DB) Day 1 and DB Week 52
Secondary	Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels	The CSF samples were obtained for measuring levels of different soluble amyloid precursor protein (sAPP) fragments (sAPP-alpha, sAPP-beta). Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage alzheimer's disease (AD) (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).	Baseline, DB Day 1 and DB Week 52
Secondary	Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels	Plasma samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length were produced by cleavage of APP by beta-secretase (BACE) and gamma-secretase complex in different peripheral tissues, including white blood cells and were measured in plasma. Participants classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).	Baseline, DB Day 1, DB Week 24, and DB Week 52
Secondary	Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level	The CSF samples were obtained for measuring levels of Tau protein and phosphorylated (p)-tau protein. Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).	Baseline, DB Day 1 and DB Week 52