EZN-2279 in Patients With ADA-SCID

• EZN-2279 (Biological), also known as rADA: Weekly administration of EZN-2279 via IM injection
• Adagen (Biological)

Primary outcomes

• 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 outcomes

• 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
• 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
• 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 [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

Sex: All

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

Participant flow

Outcome results

• Number of Patients Detoxified At Each Visit in EZN-2279 Treatment Period (Primary), Count of participants, Participants: EZN-2279 6
• Safety Summary Data (Secondary), Count of participants, Participants: Adagen 6; EZN-2279 7
• Summary of Trough ADA Activity Levels in EZN-2279 Treatment Period (Secondary), Median, mmol/h/L: EZN-2279 Treatment Period 15.7800 (13.200 to 22.900)
• Summary of Trough ADA Activity Levels in EZN-2279 Maintenance Period (Secondary), Median, mmol/h/L: EZN-2279 Treatment Period 15.7800 (13.200 to 22.900)
• Summary of Trough dAXP Levels in EZN-2279 Treatment Period (Secondary), Median, mmol/L: EZN-2279 Treatment Period 0.0020 (0.002 to 0.002)
• Summary of Trough dAXP Levels in EZN-2279 Maintenance Period (Secondary), Median, mmol/L: EZN-2279 Treatment Period 0.0020 (0.002 to 0.002)
• Number of Patients With Infections and Hospitalizations (Secondary), Count of participants, Participants: EZN-2279 5
• Duration of Hospitalization (Secondary), Mean, Days: EZN-2279 5.0 +/- 2.16
• Number of Patients Detoxified At Each Visit in EZN-2279 Maintenance Period (Secondary), Count of participants, Participants: EZN-2279 Treatment Period 6

Adverse events

Time frame: Through end of EZN-2279 study treatment, up to 203 weeks

Serious adverse events by term

Other adverse events by term

30 more terms not shown.

• Statistical Analysis Plan (PDF, 2019-04-04)
• Study Protocol (PDF, 2017-08-23)

• Elie Haddad, MD, PhD, Principal investigator, Université de Montréal