EZN-2279 in Patients With ADA-SCID

Phase 3

Completed

• Conditions: Adenosine Deaminase Deficiency; ADA-SCID; Severe Combined Immunodeficiency
• Interventions: Biological: EZN-2279; Biological: Adagen

• Registration Number: NCT01420627
• Lead Sponsor: Leadiant Biosciences, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-08-18
• Study First Submitted QC: 2011-08-18
• Study First Posted: 2011-08-19
• Study Start: 2014-01-24
• Primary Completion: 2018-04-10
• Study Completion: 2019-05-29
• Results First Submitted: 2020-03-19
• Status Verified: 2020-04
• Results First Submitted QC: 2020-04-06
• Last Update Submitted: 2020-04-06
• Results First Posted: 2020-04-16
• Last Update Posted: 2020-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adagen/EZN-2279	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
Adagen/EZN-2279	Adagen	Patients started on Adagen and crossed over to experimental EZN-2279 treatment after at least a 3 week Lead-in Period on Adagen

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Penn State College of Medicine The Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

UBMD; 🇺🇸 Buffalo, New York, United States