A study to determine if ALXN2220 is effective, safe, and tolerable in adults with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

30 Apr 2024 → ongoing

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Alexion Pharmaceuticals, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo groups as assessed by the total occurrences of ACM and CV clinical events.

Secondary objectives 8

1. To assess the effects of ALXN2220 on symptoms, functionality, and health-related QoL as measured by the change from baseline in KCCQ-OS
2. To assess the effects of ALXN2220 on CV related mortality
3. To assess the effects of ALXN2220 on change from baseline in 6MWT
4. To assess the efficacy of ALXN2220 in the treatment of ATTR-CM as assessed by the rate of CV clinical events
5. To assess the efficacy of ALXN2220 in the treatment of ATTR-CM as assessed by time to ACM
6. To assess the safety and tolerability of ALXN2220
7. To assess immunogenicity to ALXN2220
8. To characterize the PK of ALXN2220 in participants with ATTR-CM

Conditions and MedDRA coding

Adults with Transthyretin Amyloid Cardiomyopathy (ATTR-CM).

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female ≥ 18 years to ≤ 90 years of age at time of randomization.
2. Male and/or female (according to their reproductive organs and functions assigned by chromosomal complement). Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participant is eligible to participate if she is not pregnant or breastfeeding, and is a woman of nonchildbearing potential or is a WOCBP and using a highly effective contraceptive method, and agrees not to donate eggs. Male participants are eligible to participate if they agree to refrain from donating fresh unwashed semen plus abstinent from heterosexual intercourse or must agree to use contraception/barrier,
3. Diagnosis of ATTR-CM with either wild-type or a variant TTR genotype based on one of the following: a. Endomyocardial biopsy with confirmatory TTR amyloid typing by either immunohistochemistry or mass spectrometry; OR b. Grade 2 or 3 cardiac uptake on 99mTc scintigraphy (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the absence of monoclonal gammopathy; OR c. Grade 2 or 3 cardiac uptake on 99mTc scintigraphy (99mTc DPD, 99mTc PYP, or 99mTc HMDP) AND confirmatory TTR amyloid typing by either immunohistochemistry or mass spectrometry in tissue biopsy in the presence of monoclonal gammopathy
4. End-diastolic interventricular septal wall thickness ≥ 12 mm on echocardiography measured at Screening
5. NT-proBNP > 2000 pg/mL measured by a central laboratory at Screening
6. Treatment with a loop diuretic for at least 30 days prior to Screening
7. History of heart failure as documented by one of the following events within 1 year prior to Screening: a. heart failure hospitalization b. urgent heart failure visit c. episode of volume overload documented by NT-proBNP > 2000 pg/mL (or equivalent BNP)
8. NYHA Class II-IV at Screening
9. Life expectancy of ≥ 6 months as per the Investigator’s judgment
10. If treated with locally approved TTR gene silencing agent for ATTR amyloidosis (except as listed in Section 6.9.2 of the protocol), must be on a stable dose for at least 90 calendar days prior to Screening

Exclusion criteria 7

1. Known leptomeningeal amyloidosis
2. Participants with renal failure requiring dialysis or who have an eGFR by CKD-Epi formula < 20 mL/min/1.73 m2 measured by a central laboratory at Screening
3. Polyneuropathy secondary to ATTR amyloidosis requiring a wheelchair (ie, PND score IV)
4. Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis
5. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
6. Uncontrolled clinically significant cardiac arrhythmia, per Investigator's assessment.
7. LVEF < 30% on echocardiography

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Total occurrence of ACM and CV clinical events during the Blinded Treatment Period

Secondary endpoints 8

1. Change from baseline in KCCQ-OS to 24 months
2. Time to CV related mortality
3. Change from baseline in 6MWT to 24 months
4. Rate of CV clinical events
5. Time to ACM
6. Incidence of TEAEs and treatment-emergent SAEs. Changes from baseline in physical examination, vital signs, clinical laboratory tests, and 12-lead ECGs
7. ADA incidence and NAb incidence, response categories and titer
8. Serum ALXN2220 concentration

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

14 EU/EEA countries · 82 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

Documents 143 files

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

Application history

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