A Long-term Extension Study to Evaluate Safety, Tolerability, and Efficacy of AL002 in Alzheimer's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alector LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

13 Apr 2023 → 31 Jan 2025

Decision date (initial)

2025-01-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Alector LLC

External identifiers

EU CT number

2023-506872-29-00

EudraCT number

2022-002987-57

ClinicalTrials.gov

NCT05744401

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the long-term safety and tolerability of AL002 in participants with Alzheimer's disease (AD) and to evaluate the effect of immunogenicity to AL002 on safety, PK, and PD biomarkers in participants with AD

Conditions and MedDRA coding

Alzheimer's Disease

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. The participant has completed the planned treatment period in the AL002-2 study. Completion of the planned treatment period is defined as any participant who did not prematurely and permanently discontinue the study drug in the AL002-2 study.
2. The participant is willing and able to give informed consent. Where local regulations permit inclusion of participants deemed not able to provide informed consent, a legally authorized representative must provide informed consent on his or her behalf, and the participant must provide assent, in accordance with the local regulations, guidelines, and institutional review board or independent ethics committee.
3. Female participants must be nonpregnant and nonlactating, and 1 of the following conditions must apply: a. Participant is not a woman of childbearing potential (WOCBP) (either surgically sterilized, or physiologically incapable of becoming pregnant, or at least 1-year postmenopausal [amenorrhea duration of 12 consecutive months with no identified cause other than menopause]). b. Participant is a WOCBP and agrees to use an acceptable contraceptive method from screening until 12 weeks after the last dose of study drug. Acceptable contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom, or the sole sexual partner to a vasectomized male. Vasectomized males must have received medical assessment of surgical success. In addition, total abstinence, in accordance with the lifestyle of the participant, is acceptable. c. A WOCBP must have a serum pregnancy test conducted at screening. Additional requirements for pregnancy testing during and after study intervention are described in the Schedules of Assessments.
4. Male participants must agree to use acceptable contraception and not donate sperm from screening until 12 weeks after the last dose of study drug. Acceptable contraception for the male participant when having sexual intercourse with a WOCBP who is not currently pregnant is defined as using a condom. In addition, WOCBP partners must use hormonal contraceptives or an intrauterine device. Vasectomized male participants should have received medical assessment of surgical success.
5. Participant weighs ≤120 kg; body mass index (BMI) is between 18.5 and 34.9 kg/m2 inclusive.
6. The participant has availability of a person (“study partner”) who, in the Investigator’s opinion, has frequent and sufficient contact with the participant (eg, at least 10 hours per week of in person contact), is able to provide accurate information regarding the participant’s cognitive and functional abilities, agrees to provide information at clinic visits (which require partner input for scale completion), and signs the necessary consent form. a. The study partner must have sufficient cognitive capacity, in the Investigator’s opinion, to accurately report upon the participant’s behavior, cognitive, and functional abilities. The study partner should be in sufficiently good general health, in the Investigator’s opinion, to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the study duration. b. Every effort should be made to have the same study partner participate throughout the duration of the study, and to have the same study partner as in the parent study.
7. The participant and study partner are fluent in the language of the tests used at the study site as assessed by site personnel.
8. The participant is willing and able to complete all aspects of the study (including MRI). The participant should be capable of completing assessments either alone or with the help of the study partner. Participants whose disease has progressed such that they cannot complete the efficacy assessments may participate in the study for assessment of safety.
9. The participant has adequate visual and auditory acuity, in the Investigator’s opinion, sufficient to perform the neuropsychological testing (corrective lenses and hearing aids are permitted).
10. Participant agrees not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study drug
11. Inclusion criteria for participants in the optional Tau PET imaging assessment with [18F]MK- 6240 only: Participant has not had excessive radiation exposure prior to enrollment in the trial, as defined by local standards.
12. Inclusion criteria for participants in the optional Tau PET imaging assessment with [18F]MK- 6240 only: [18F]MK-6240 is available to the PET imaging center based on manufacturing distribution network and local regulations.
13. Inclusion criteria for participants in the optional longitudinal Amyloid PET imaging assessment only: Participant has not had excessive radiation exposure prior to enrollment in the trial, as defined by local standards.
14. Inclusion criteria for participants in the optional longitudinal Amyloid PET imaging assessment only: An approved amyloid radiotracer is available to the PET imaging center based on manufacturing distribution network and local regulations.

Exclusion criteria 7

1. Participants deemed not able to provide consent or assent by the Investigator or by local regulations.
2. Participants who were prematurely and permanently discontinued from IMP in the parent study for safety reasons.
3. The participant has MRI evidence of: a. >2 lacunar infarcts. b. Any territorial infarct >1 cm^3. c. White matter hyperintense lesions on the FLAIR sequence that correspond to an overall Fazekas score of 3. d. Participants who have an increase in their number of microbleeds, since the previous screening/ baseline MRI in the AL002-2 study and greater than 5, should be discussed with the Medical Monitor. e. Participants who have developed ARIA-E and ARIA-H in the parent study and who were permitted to continue dosing according to the ARIA management guidelines, will not be excluded from participation in the AL002-LTE, on the basis of microbleeds or hemosiderosis.
4. Anticoagulant medications other than antiplatelet agents are prohibited within 90 days of screening and throughout the study. Short-term use of anticoagulants to treat an emergent medical need is permitted. Treatment with platelet anti-aggregation agents such as aspirin, clopidogrel, or dipyridamole is permitted.
5. Participants taking any passive immunotherapy (eg, immunoglobulin) or other long-acting biologic agent that is under evaluation or approved to prevent or postpone cognitive decline.
6. Participation in the AL002-LTE is deemed inappropriate for any reason per Investigator discretion.
7. Participant agrees not to receive any investigational treatment, other than AL002, during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence of AEs, including AESIs and SAEs
2. Vital signs, clinical laboratory results, and incidence of findings from physical, neurological, ophthalmological examinations, and ECG
3. C-SSRS
4. MRI abnormalities
5. Incidence and severity of ARIA in participants undergoing titration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alector LLC

Sponsor organisation

Alector LLC

Address

131 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-2029

Country

United States

Scientific contact point

Organisation

Alector LLC

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Alector LLC

Contact name

Clinical Trial Information Desk

Third parties 13

Locations

6 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 113 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications