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A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation

Trial Profile

A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation

Status: Active, no longer recruiting
Phase of Trial: Phase I

Latest Information Update: 12 Aug 2019

At a glance

  • Drugs AL 001 (Primary)
  • Indications Dementia
  • Focus Adverse reactions; First in man
  • Acronyms INFRONT
  • Sponsors Alector
  • Most Recent Events

    • 12 Aug 2019 Status changed from recruiting to active, no longer recruiting (in Jul 2019), according to an Alector media release.
    • 18 Apr 2019 Planned End Date changed from 30 Sep 2020 to 31 Dec 2019.
    • 18 Apr 2019 Planned primary completion date changed from 30 Mar 2020 to 31 Dec 2019.

Trial Overview

Purpose

This phase I/Ib, first in human trial is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenously administered AL001 in healthy volunteers and participants with frontotemporal dementia that carry the GRN mutation, known as FTD-GRN.
The study is designed to assess single and multiple doses of AL001 and measure the levels of progranulin, a disease specific biomarker, in plasma and in cerebrospinal fluid.

Primary Endpoints

Evaluation of safety and tolerability of AL001 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs)

description: Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods.
time_frame: 85 days

Other Endpoints

Pharmacokinetics (PK) of AL001

description: Serum and CSF concentration of AL001 at specified time points
time_frame: 85 days

Maximum plasma concentration (Cmax) for AL001

description: Evaluate Cmax for serum and CSF concentration of AL001 at specified time points
time_frame: 85 days

Area under the curve concentration (AUC) for AL001

description: Evaluate AUC for serum and CSF concentration of AL001 at specified time points
time_frame: 85 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
Dementia treatment -

Subjects

  • Subject Type patients & volunteers
  • Number

    Planned: 60

  • Sex male & female
  • Age Group 18-80 years; adult; elderly

Patient Inclusion Criteria

- BMI 18.0-35.0 kg/m2 - 45-120 kg, inclusive - At screening, females must be non-pregnant and non-lactating, or of nonchildbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1-year postmenopausal (amenorrhoea duration of 12 consecutive months); nonpregnancy will be confirmed for all females by a pregnancy test conducted at screening, (each) admission, and at follow-up. - Female participants of child-bearing potential must agree to use adequate contraception from screening until 90 days after the follow-up visit. A - In good physical health on the basis of no clinically significant findings from medical history, physical examination (PE), laboratory tests, 12 lead ECG, and vital signs, as judged by the Investigator. - Willingness and able to comply with the study protocol, in the investigator's judgement.

Patient Exclusion Criteria

- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins. - Positive drug or alcohol at screening and prior to first dose - History of alcohol abuse or substance abuse

Trial Details

Identifiers

Identifier Owner
NCT03636204 ClinicalTrials.gov: US National Institutes of Health
AL001-1 -

Organisations

  • Sponsors Alector
  • Affiliations Alector

Trial Dates

  • Initiation Dates

    Planned : 15 Sep 2018

    Actual : 14 Sep 2018

  • Primary Completion Dates

    Planned : 31 Dec 2019

  • End Dates

    Planned : 31 Dec 2019

Other Details

  • Design double-blind; multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase I
  • Location Canada; England; USA
  • Focus Adverse reactions; First in man

Interventions

Drugs Route Formulation
AL 001Primary Drug Intravenous
-

AL001

Up to six single ascending doses of AL001 Biological: AL001 (Active dose of AL001)

Saline Solution

Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects Other: Placebo (Saline solution administered as a single infusion as palcebo.)

Results

Therapeutic efficacy

Results from the single ascending dose part of the phase I trial of AL 001, demonstrated dose dependent increase in PGRN levels in plasma and in cerebrospinal fluid in healthy volunteers and in patients with frontotemporal dementia [2] .

Results from the phase I INFRONT study showed that AL 001 was able to restore the level of progranulin in patients with frontotemporal dementia with a granulin mutation back to the normal range [3] .

Adverse events

Results from phase I INFRONT study showed that AL 001 was well tolerated and was safe in patients with frontotemporal dementia with a granulin mutation [3] .

In a phase I trial, AL 001 was generally safe and well tolerated through the highest dose assessed, healthy volunteers and in patients with frontotemporal dementia [2] .

Publications

  1. Paul R, Ward M, Siddiqui O, Hagey M, Long H, King R, et al. A phase 1 study of AL001 in healthy volunteers and frontotemporal dementia patients carrying a granulin mutation. AAIC-2019 2019; abstr. 35586.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=35586
  2. Alector. Alector Announces Data from On-going Phase 1b Trial Demonstrating that AL001 Reverses Progranulin Deficiency in Frontotemporal Dementia Patients. Media-Rel 2019;.

    Media Release
  3. Alector. Alector Announces First Frontotemporal Dementia Patient Dosed in Phase 1b Study of AL001. Media-Rel 2017;.

    Media Release

Authors

Author Total Publications First Author Last Author
Alector 2 2 2
Hagey M 1 - -
King R 1 - -
Kurnellas M 1 - -
Long H 1 - -
Lu S-P 1 - -
Paul R 1 1 -
Rosenthal A 1 - 1
Schwabe T 1 - -
Siddiqui O 1 - -
Ward M 1 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
George Stoica Bioclinica Research
-
Study Coordinator
+1-519-685-4292 cognitiveneurology@sjhc.london.on.ca
show details
Lawson Health Research Institute, St. Joseph's, Mayo Clinic, Sunnybrook Health Sciences Centre, UCSF, University College London, University of Alabama, University of Pennsylvania Canada, United-Kingdom, USA
Study Lead
4152315660 Ext: 328 info@alector.com
show details
Alector Inc.
-

Centres

Centre Name Location Trial Centre Country
Alector Inc.
-
-
Bioclinica Research
-
-
Lawson Health Research Institute, St. Joseph's London, Ontario Canada
Mayo Clinic Rochester, Minnesota USA
Study site Orlando, Florida USA
Sunnybrook Health Sciences Centre Toronto Canada
UCSF San Francisco, California USA
University College London London United-Kingdom
University of Alabama Birmingham, Alabama USA
University of Pennsylvania Philadelphia, Pennsylvania USA

Trial History

Event Date Event Type Comment
12 Aug 2019 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting (in Jul 2019), according to an Alector media release. Updated 09 Oct 2019
18 Jul 2019 Results Results from the single ascending dose (SAD) presented at the Alzheimer's Association International Conference 2019 Updated 23 Oct 2019
17 Jul 2019 Interim results According to an Alector media release, data from this study (n=50 healthy volunteers and n=4 patients with FTD-GRN) were presented today at the 2019 Alzheimer's Association International Conference (AAIC) by Robert Paul, M.D., Ph.D., (chief medical officer of Alector). Updated 10 Oct 2019
17 Jul 2019 Interim results Results from ongoing phase 1b portion of this trial (n=50 healthy volunteers and n=4 patients with FTD-GRN) presented in an Alector media release. Updated 10 Oct 2019
22 Apr 2019 Other trial event Last checked against ClinicalTrials.gov record. Updated 22 Apr 2019
18 Apr 2019 Completion date Planned End Date changed from 30 Sep 2020 to 31 Dec 2019. Updated 22 Apr 2019
18 Apr 2019 Other trial event Planned primary completion date changed from 30 Mar 2020 to 31 Dec 2019. Updated 22 Apr 2019
17 Apr 2019 Interim results Results of phase I healthy volunteer portion of this study presented in an Alector media release. Updated 10 Oct 2019
17 Apr 2019 Other trial event According to an Alector media release, the first frontotemporal dementia (FTD) patient has been dosed in the Phase 1b portion of this trial after successful completion of the healthy volunteer single ascending dose escalation portion of the study. Updated 09 Oct 2019
19 Sep 2018 Status change - recruiting Status changed from not yet recruiting to recruiting, according to an Alector media release. Updated 09 Oct 2019
24 Aug 2018 New trial record New trial record Updated 24 Aug 2018

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Paul R, Ward M, Siddiqui O, Hagey M, Long H, King R, et al. A phase 1 study of AL001 in healthy volunteers and frontotemporal dementia patients carrying a granulin mutation. AAIC-2019 2019; abstr. 35586.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=35586
  3. Alector. Alector Announces Data from On-going Phase 1b Trial Demonstrating that AL001 Reverses Progranulin Deficiency in Frontotemporal Dementia Patients. Media-Rel 2019;.

    Media Release
  4. Alector. Alector Initiates Phase 1 Trial of AL001 for the Treatment of Frontotemporal Dementia. Media-Rel 2019;.

    Media Release
  5. Alector. Alector Announces First Frontotemporal Dementia Patient Dosed in Phase 1b Study of AL001. Media-Rel 2017;.

    Media Release
  6. Alector. Alector Reports Recent Business Highlights and Second Quarter 2019 Financial Results. Media-Rel 2019;.

    Media Release
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