EZN-2279 in Patients With ADA-SCID

A Study of EZN-2279 (Polyethylene Glycol Recombinant Adenosine Deaminase [PEG-rADA]) Administered as a Weekly Intramuscular Injection in Patients With Adenosine Deaminase (ADA)-Deficient Combined Immunodeficiency

The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of EZN-2279 in patients with ADA-deficient combined immunodeficiency currently being treated with Adagen.

Study Overview

• Status: Completed
• Conditions: Severe Combined Immunodeficiency; ADA-SCID; Adenosine Deaminase Deficiency
• Intervention / Treatment: Biological: EZN-2279; Biological: Adagen

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Colorado
    • Denver, Colorado, United States, 80206-2761
      • National Jewish Health
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • Buffalo, New York, United States, 14203
      • UBMD
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine The Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of ADA-deficient combined immunodeficiency
2. Stable clinical status while receiving therapy with Adagen®. Patients previously receiving gene therapy or undergoing hematopoietic stem cell transplantation who still require Adagen® treatment are eligible. The dose of Adagen® must be stable for at least 6 months prior to study entry.

3. Have both of the following during the Adagen® Lead-in phase of the study prior to EZN-2279 transition:

   1. Trough plasma ADA activity >15 μmol/h/mL while receiving Adagen® and
   2. Total erythrocyte dAXP ≤0.02 μmol/mL from a trough blood sample
4. Patients or parent/guardian must be capable of understanding the protocol requirements and risks and providing written informed assent/consent

Exclusion Criteria:

1. Autoimmunity requiring immunosuppressive treatment
2. Patients with detectable neutralizing anti-Adagen® antibodies at screening evaluation
3. Severe thrombocytopenia (platelet count <50 x 10^9/L)
4. Current participation in other therapeutic protocols for ADA-deficient combined immunodeficiency
5. Current or prior participation in another clinical study with an investigational agent and/or use of an investigational drug in the 30 days before study entry
6. Known planned participation in a gene-therapy study for the planned duration of this study
7. Any condition that, in the opinion of the PI, makes the patient unsuitable for the study
8. Inability or unwillingness to administer Adagen® or EZN-2279 on a one-time-per-week regimen
9. Inability to comply with the study protocol
10. Female patients who are pregnant or lactating
11. Female patients who are breast-feeding
12. Female subjects of childbearing potential who are not using an FDA approved birth control method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adagen/EZN-2279; Patients started on Adagen and crossed over to experimental EZN-2279 treatment after at least a 3 week Lead-in Period on Adagen	Biological: EZN-2279; Weekly administration of EZN-2279 via IM injection; Other Names: rADA; Biological: Adagen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Detoxified At Each Visit in EZN-2279 Treatment Period	Number of patients with total erythrocyte dAXP concentration from a trough blood sample <0.02 mmol/L	Baseline through Week T-21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Summary Data	Summary of adverse events and serious adverse events	Through end of EZN-2279 study treatment, up to 203 weeks
Summary of Trough ADA Activity Levels in EZN-2279 Treatment Period	Trough ADA activity, mmol/h/L	From Baseline through Week T-21
Summary of Trough ADA Activity Levels in EZN-2279 Maintenance Period	Trough ADA activity levels, mmol/h/L	Through end of EZN-2279 study treatment, up to 203 weeks
Summary of Trough dAXP Levels in EZN-2279 Treatment Period	Trough dAXP levels, mmol/L	From Baseline through Week T-21
Summary of Trough dAXP Levels in EZN-2279 Maintenance Period	Trough dAXP levels, mmol/L	Through end of EZN-2279 study treatment, up to 203 weeks
Number of Patients With Infections and Hospitalizations	Infections were documented clinically with signs and symptoms without microbiologic cultures or with positive viral or bacterial cultures	Through end of EZN-2279 study treatment, up to 203 weeks
Duration of Hospitalization		Through end of EZN-2279 study treatment, up to 203 weeks
Number of Patients Detoxified At Each Visit in EZN-2279 Maintenance Period	Number of patients with total erythrocyte dAXP concentration from a trough blood sample <0.02 mmol/L	From Week 34 to End of Study/Early Discontinuation, up to 203 weeks

Collaborators and Investigators

• Sponsor: Leadiant Biosciences, Inc.
• Investigators: Principal Investigator: Elie Haddad, MD, PhD, Université de Montréal

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2014
• Primary Completion (Actual): April 10, 2018
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: August 18, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 19, 2011

Study Record Updates

• Last Update Posted (Actual): April 16, 2020
• Last Update Submitted That Met QC Criteria: April 6, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Severe Combined Immunodeficiency
• Other Study ID Numbers: STP-2279-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No