EZN-2279 in Patients With ADA-SCID

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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ADA-SCID, Adenosine Deaminase Deficiency, Severe Combined Immunodeficiency

Intervention / Treatment
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* Biological: EZN-2279
* Biological: Adagen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ADA-deficient combined immunodeficiency 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. Have both of the following during the Adagen® Lead-in phase of the study prior to EZN-2279 transition: Trough plasma ADA activity >15 μmol/h/mL while receiving Adagen® and Total erythrocyte dAXP ≤0.02 μmol/mL from a trough blood sample Patients or parent/guardian must be capable of understanding the protocol requirements and risks and providing written informed assent/consent Exclusion Criteria: Autoimmunity requiring immunosuppressive treatment Patients with detectable neutralizing anti-Adagen® antibodies at screening evaluation Severe thrombocytopenia (platelet count <50 x 10^9/L) Current participation in other therapeutic protocols for ADA-deficient combined immunodeficiency 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 Known planned participation in a gene-therapy study for the planned duration of this study Any condition that, in the opinion of the PI, makes the patient unsuitable for the study Inability or unwillingness to administer Adagen® or EZN-2279 on a one-time-per-week regimen Inability to comply with the study protocol Female patients who are pregnant or lactating Female patients who are breast-feeding Female subjects of childbearing potential who are not using an FDA approved birth control method
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adagen/EZN-2279<br>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<br>* Weekly administration of EZN-2279 via IM injection<br>* Other names: rADA;Biological: Adagen<br> <br> |

What is the study measuring?
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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 |