Clinical Trials

A new investigational drug, INZ-701, is currently in clinical trials for infants, children, and adults.  The infant and pediatric trials are still enrolling patients with ENPP1 Deficiency.  More information about the studies and study sites is available below.

THE ENERGY STUDY FOR INFANTS
(currently recruiting)


STUDY OVERVIEW

Study INZ701-104 (The ENERGY Study) is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of an investigational ENPP1 enzyme therapy, INZ-701, in infant subjects (from birth to 1 year) with ENPP1 Deficiency. For more information, visit clinicaltrials.gov.


FIND A STUDY SITE

BOSTON

Boston Children’s Hospital

Boston, Massachusetts, United States, 02115.

Contact: Alayna Dutcher
+1-617-355-0741
alayna.dutcher@childrens.harvard.edu

Contact: Andrea Hale, RN, MHP
+1-617-919-2867
andrea.hale@childrens.harvard.edu


CALIFORNIA

Rady Children’s Hospital

San Diego, CA, United States.

Contact: Phoebe Chandler
+1-858-576-1700 ext. 220096
pchandler@rchsd.org


OHIO

Nationwide Children’s Hospital

Columbus, Ohio, United States.

Contact: Bimal Chaudhari, MD
+1-614-722-3535
bimal.chaudhari@nationwidechildrens.org

Contact: Marina Artemova, PhD
+1-614-722-2655
marina.artemova@nationwidechildrens.org


PENNSYLVANIA

CHOP – The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104.

Contact: Maximilian Krumpholz
+1-267-432-0511
krumpholm1@chop.edu

Contact: Rachel Walega
+1-267-586-5969
walegar1@chop.edu

UNITED KINGDOM

Royal Manchester Children’s Hospital

Manchester, United Kingdom

Principal Investigator:  Dr Amish Chinoy

Contact:  Charlotte Boe
charlotte.boe@mft.nhs.uk

THE ENERGY 3 STUDY FOR CHILDREN
(currently recruiting)


STUDY OVERVIEW

Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children (aged 1 year to 12 years) with ENPP1 Deficiency. For more information, visit clinicaltrials.gov.


FIND A STUDY SITE

BOSTON

Boston Children’s Hospital

Boston, Massachusetts, United States, 02115.

Contact: Alayna Dutcher
+1-617-355-0741
alayna.dutcher@childrens.harvard.edu

Contact: Andrea Hale, RN, MHP
+1-617-919-2867
andrea.hale@childrens.harvard.edu


CHICAGO

Ann & Robert  H. Lurie Children’s Hospital

Chicago, Illinois, United States.

Principal Investigator: Dr. Jennie Miller

Contact: Madeleine Muller
 mmuller@luriechildrens.org


COLORADO

Children’s Hospital Colorado

Children’s Hospital Colorado

Principal Investigator:  Dr Nina Ma MD
+1-720-777-0780

Nina.Ma@childrenscolorado.org 

Coordinators:

Matt Brien
matthew.brien@childrenscolorado.org
Beni Garcia
benigno.garcia@childrenscolorado.org 


OHIO

Nationwide Children’s Hospital

Columbus, Ohio, United States.

Principal Investigator: Dr. Bimal Chaudhari

Contact: Kaitlyn Brown RN, BSN
Clinical Research Nurse

+1-614-722-2286
Kaitlyn.Brown2@nationwidechildrens.org


PENNSYLVANIA

CHOP – The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104.

Principal Investigator:  Dr. David Weber

Contact: Maximilian Krumpholz
krumpholm1@chop.edu


TEXAS

Cook Children’s Hospital

Fort Worth, Texas, United States, 76104.

Principal Investigator:  Dr. Joel Steelman
+1-682-885-1951
joel.steelman@cookchildrens.org

MONTREAL

CHU Sainte-Justine

Montreal, Quebec, Canada.

Principal Investigator: Dr. Nathalie Alos

Contact: Michna Alphonse Kenny
 kenny-michna.alphonse.hsj@ssss.gouv.qc.ca

FRANCE

Hôpital Bicêtre

Paris, France.

Principal Investigator: Agnès Linglart
agnes.linglart@aphp.fr


UNITED KINGDOM

Royal Manchester Children’s Hospital

Manchester, United Kingdom

Principal Investigator:  Dr Amish Chinoy

Contact:  Annie Tariq
+44 161 701 8558
annie.tariq@mft.nhs.uk

ENERGY-3 Pivotal Clinical Trial Webinar

The following is a webinar presented on August 19th, 2023, by GACI Global and Inozyme Pharma to the GACI Global community of patients and families affected by GACI & ARHR2.  The webinar gives information about the ENERGY-3 Pivotal Clinical Trial for Pediatric Patients Aged 1yr-<13yrs with ENPP1 Deficiency.  If you have any questions on the webinar, please email them us us at info@gaciglobal.org.

There is a new investigational drug, INZ-701, currently in clinical trials for infants, children, and adults.  The infant and pediatric trials are still enrolling patients with ENPP1 Deficiency.  More information about the studies and study sites is available below.

THE ENERGY STUDY FOR INFANTS
(currently recruiting)


STUDY OVERVIEW

Study INZ701-104 (The ENERGY Study) is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of an investigational ENPP1 enzyme therapy, INZ-701, in infant subjects (from birth to 1 year) with ENPP1 Deficiency. For more information, visit clinicaltrials.gov.


FIND A STUDY SITE


Boston Children’s Hospital

Boston, Massachusetts, United States, 02115.

Contact: Alayna Dutcher
+1-617-355-0741
alayna.dutcher@childrens.harvard.edu

Contact: Andrea Hale, RN, MHP
+1-617-919-2867
andrea.hale@childrens.harvard.edu


The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104.

Contact: Maximilian Krumpholz
+1-267-432-0511
krumpholm1@chop.edu

Contact: Rachel Walega
+1-267-586-5969
walegar1@chop.edu

Nationwide Children’s Hospital

Columbus, Ohio, United States.

Contact: Bimal Chaudhari, MD
+1-614-722-3535
bimal.chaudhari@nationwidechildrens.org

Contact: Marina Artemova, PhD
+1-614-722-2655
marina.artemova@nationwidechildrens.org

THE ENERGY 3 STUDY FOR CHILDREN
(currently recruiting)


STUDY OVERVIEW

Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children (aged 1 year to 12 years) with ENPP1 Deficiency. For more information, visit clinicaltrials.gov.


FIND A STUDY SITE


UNITED STATES

The Children’s Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States, 19104.

Principal Investigator:  Dr. David Weber

Contact: Maximilian Krumpholz
krumpholm1@chop.edu

Cook Children’s Hospital

Fort Worth, Texas, United States, 76104.

Principal Investigator:  Dr. Joel Steelman

Contact:  Dr. Joel Steelman
+1-682-885-1951
joel.steelman@cookchildrens.org


Ann & Robert  H. Lurie Children’s Hospital

Chicago, Illinois, United States.

Principal Investigator: Dr. Jennie Miller

Contact: Madeleine Muller
 mmuller@luriechildrens.org


CANADA


CHU Sainte-Justine

Montreal, Quebec, Canada.

Principal Investigator: Dr. Nathalie Alos

Contact: Michna Alphonse Kenny
 michna.alphonse.hsj@ssss.gouv.qc.ca

ENERGY-3 Pivotal Clinical Trial Webinar

The following is a webinar presented on August 19th, 2023, by GACI Global and Inozyme Pharma to the GACI Global community of patients and families affected by GACI & ARHR2.  The webinar gives information about the ENERGY-3 Pivotal Clinical Trial for Pediatric Patients Aged 1yr-<13yrs with ENPP1 Deficiency.  If you have any questions on the webinar, please email them us us at info@gaciglobal.org.

Ultra-Rapid Genetic Testing

Inozyme Pharma is sponsoring ultra-rapid genetic testing at Rady Children’s Institute for Genomic Medicine® for infants suspected of having GACI.  GACI is characterized by narrowing of large and medium arteries caused by severe and pathological vascular calcification and neointimal proliferation, resulting in dysfunction and potential failure of major organs, such as the heart, lungs, and kidneys.

To access the sponsored genetic testing program for infants under 1 year old, please reach out to Catherine Nester, Inozyme Pharma at catherine.nester@inozyme.com or +1-717-587-0845 Please click here to print out a leaflet with this information.

Patients under 1 year of age with these symptoms may qualify for sponsored ultra-rapid genetic testing:

ABCC6 Deficiency

Age-dependent manifestations of ABCC6 Deficiency (GACI type 2 and PXE)

ABCC6 Deficiency disorder is also characterized by low PPi levels and may sometimes manifest as GACI type 2 in infants.  In infants with ABCC6 Deficiency (GACI type 2 phenotype), the ability to inhibit ectopic calcification is lost due to low PPi levels, resulting in pathological soft tissue calcification, including mineralization of the arteries, heart, kidneys, and joints.  This process of ectopic calcification usually begins in utero or within the first few weeks of life.  Infants who survive the first 6 months have a much lower risk of death1, likely due to reduced arterial blood flow resistance as infants age.

ABCC6 Deficiency is most likely manifest as Pseudoxanthoma Elasticum (PXE) in the post-infancy stage.  PXE is a disorder that causes select elastic tissue in the body to become mineralized due to calcium and other minerals being deposited in the tissue.  This can result in changes in the skin and eyes.

ENPP1 Deficiency

Age-dependent manifestations of ENPP1 Deficiency (GACI type 1 and ARHR2)

Depending on age, ENPP1 Deficiency can manifest as two phenotypes due to the interaction between low plasma PPi and age-dependent normal or compensatory physiological changes.  In infants with ENPP1 Deficiency (GACI type 1 phenotype), the ability to inhibit ectopic calcification is lost due to low PPi levels, resulting in pathological soft tissue calcification, including mineralization of the arteries, heart, kidneys, and joints.  This process of ectopic calcification usually begins in utero or within the first few weeks of life.  Infants who survive the first 6 months have a much lower risk of death1, likely due to reduced arterial blood flow resistance as infants age.

Infants with ENPP1 Deficiency who survive GACI type 1 will almost all develop ARHR2, usually beginning between ages 2–8 years.  ARHR2 is a skeletal disorder that is characterized by rickets, bone and muscle pain, bowing of the legs, short stature, and an increased risk of fractures.  It is hypothesized that children with ENPP1 Deficiency develop a state of low phosphate in their serum, known as hypophosphatemia, as a compensatory mechanism for the state of low PPi in order to inhibit or decrease ectopic calcification1.  This hypophosphatemia leads to rickets in affected children.

The role of pyrophosphate in preventing pathogenic mineralization

ENPP1 Deficiency is caused by loss of function mutations in the ENPP1 gene that leads to decreased levels or activity of ENPP1 enzyme.  ENPP1 enzyme cleaves adenosine triphosphate (ATP) to generate adenosine monophosphate (AMP) and inorganic pyrophosphate (PPi), a molecule essential for preventing harmful soft tissue calcification and for regulating bone mineralization5,6. Therefore, a decrease in PPi levels causes a disease state exhibiting both ectopic (especially vascular) calcification in infants (GACI phenotype) and defects in bone mineralization (ARHR2 phenotype) post-infancy.

There is a substantial body of evidence that documents PPi as an endogenous inhibitor of calcification5,6.  Specifically, PPi potently inhibits the ability of calcium to crystallize with phosphate to form hydroxyapatite (HA), the main mineral component of bone, in soft tissue.  PPi prevents the initiation of mineralization in soft tissue by binding strongly to the surface of HA crystals and blocking HA crystals from growing, thereby preventing the initial mineralization and further harmful soft tissue calcification.  Therefore, it is the low level of PPi that permits pathological mineralization in vascular smooth muscle tissue.  The ability of PPi to inhibit calcification and its essential role in preventing harmful soft tissue calcification is highlighted in ENPP1 Deficiency where low PPi levels allow for ectopic calcification.  Low levels of plasma PPi are linked with abnormalities in bone microstructure7,8 leading to ARHR2 (rickets)1.

References

  1. Rutsch F, Böyer P, Nitschke Y, Ruf N, Lorenz-Depierieux B, Wittkampf T, Weissen-Plenz G, Fischer RJ, Mughal Z, Gregory JW, Davies JH, Loirat C, Strom TM, Schnabel D, Nürnberg P, Terkeltaub R; GACI Study Group. “Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy.” Circ Cardiovasc Genet. 2008 Dec;1(2):133-40. View Link.
  1. Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. “ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.” Nat Commun. 2015 Dec 1;6:10006. View Link.
  1. Khan T, Sinkevicius KW, Vong S, Avakian A, Leavitt MC, Malanson H, Marozsan A, Askew KL. “ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy.” Dis Model Mech. 2018 Oct 8;11(10). View Link.
  1. https://www.inozyme.com/wp-content/uploads/2019/04/Series-A2-Financing-News-Release-Final-Apr-09-2019-1700.pdf
  2. Orriss, IR, Arnett TR, Russell RG. “Pyrophosphate: a key inhibitor of mineralisation.” 2016 Curr Opin Pharmacol 28:57-68. View Link.
  3. Fleisch H, Russell RG, Straumann F. “Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis.” Nature. 1966 Nov 26;212(5065):901-3. View Link.
  4. Mackenzie, NC, Huesa C, Rutsch F, MacRae VE. “New insights into NPP1 function: lessons from clinical and animal studies.” 2012 Bone 51 (5):961-8. View Link.
  5. Hajjawi, M O, MacRae VE, Huesa C, Boyde A, J. Millan JL, Arnett TR, and Orriss IR. “Mineralisation of collagen rich soft tissues and osteocyte lacunae in ENPP1(-/-) mice.” 2014 Bone 69:139-47. View Link.