The ENERGY 2 Study: A study to investigate if study drug INZ-701 increases survival in infants with ENPP1 Deficiency by preventing heart dysfunction and calcification of arteries

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inozyme Pharma Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

24 Oct 2024 → ongoing

Decision date (initial)

2024-09-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Inozyme Pharma Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

• To determine if INZ-701 increases inorganic pyrophosphate (PPi) levels
• To determine if INZ-701 increases overall survival compared to the Natural History Database

Secondary objectives 6

1. To determine if INZ-701 prevents decline in cardiac ejection fraction
2. To determine if INZ-701 prevents heart failure
3. To determine if INZ-701 attenuates progression of arterial calcification
4. To determine if INZ-701 increases physical growth: body length and weight
5. To determine if INZ-701 prevents respiratory dysfunction
6. To characterize the PK and ENPP1 activity of INZ-701

Conditions and MedDRA coding

Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003232-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Caregiver(s) written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per International Council on Harmonisation (ICH) Good Clinical Practice (GCP)
2. A confirmed postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed using assays that meet CE-marked requirements, or by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory, or a regional equivalent
3. Clinical manifestations of GACI, which must include at least one of the following: ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly. Heart failure is defined as a structural and/or functional abnormality that produces raised intracardiac pressures and/or inadequate cardiac output resulting in characteristic signs and symptoms including edema and respiratory distress. Cardiomegaly is defined as cardiothoracic ratio exceeding 0.5 by chest X-ray or increased left ventricular mass on echocardiography or cross-sectional imaging relative to normal based on Investigator judgment.
4. Males and females from birth to <1 year of age at Study Day 1
5. Plasma PPi concentration of <1400 nM: a. at study Screening if study participant has not participated in the EAP. b. at the documented baseline prior to treatment with INZ-701 in the EAP
6. Body weight ≥0.5 kg at the time of the first dose of INZ-701
7. Be able to complete all aspects of the study in the opinion of the Investigator
8. Caregiver(s) agree to provide access to their infant’s relevant medical records

Exclusion criteria 6

1. In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality not associated with ENPP1 Deficiency that will preclude study participation and/or may confound interpretation of study results
2. Care has been withdrawn or infant is receiving end of life or hospice care
3. Planned surgery that may confound the interpretation of study results during the 52-week Treatment Period in the opinion of the Investigator
4. Known intolerance to INZ-701 or any of its excipients
5. Previous treatment with INZ-701 unless prior treatment was part of the EAP, in which case they may participate upon Sponsor approval
6. Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from Baseline in plasma PPi concentration through Week 52
2. Overall survival based on time from date of birth to event of all-cause mortality through Week 52

Secondary endpoints 7

1. Change from Baseline in left ventricular ejection fraction via echocardiography through Week 52
2. Incidence of heart failure
3. Change from Baseline in vascular calcification in the coronary arteries and aorta via CT scan through Week 52
4. Change from Baseline in growth Z-score (body length and weight) through Week 52
5. Growth velocity
6. Number of days of mechanical ventilation
7. Measurement of INZ-701 plasma concentration and ENPP1 activity

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inozyme Pharma Inc.

Sponsor organisation

Inozyme Pharma Inc.

Address

321 Summer Street

City

Boston

Postcode

02210-1725

Country

United States

Scientific contact point

Organisation

Inozyme Pharma Inc.

Contact name

Jack Brownrigg, MBChB, PhD

Public contact point

Organisation

Inozyme Pharma Inc.

Contact name

Clinical Trial Information

Third parties 12

Locations

5 EU/EEA countries · 5 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 55 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