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This registry study is being conducted in patients with adenosine deaminase severe combined immune deficiency (ADA-SCID) who require enzyme replacement therapy (ERT) treatment with Revcovi. Data on safety and on measures of efficacy are collected.
Patients with ADA-SCID who require ERT will receive Revcovi on a dosage and schedule determined by the treating physician. They will be followed for safety throughout the study, and will be monitored for the efficacy markers of adenosine deaminase (ADA) activity and deoxyadenosine nucleotide (dAXP) concentration according to a suggested schedule. Some subjects will be new to ERT; some will have transitioned from Adagen, which was the ERT available before Revcovi; and some will have previously participated in an earlier Phase 3 trial of Revcovi (study STP-2279-002). Patients will be followed either until they are able to successfully undergo a stem cell transplant or stem cell gene therapy and thus no longer require ERT treatment, or until all ongoing participants have received a minimum of 24 months of Revcovi treatment.
Note: Due to the nature of this study, all analyses are descriptive and no statistical hypotheses will be tested.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with ADA-SCID in need of ERT treatment | All participants will receive Revcovi. For analysis purposes, there will be three groups, who differ with respect to ERT history:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| elapegademase-lvlr | Biological | Revcovi is administered intramuscularly (i.m.). Weekly dosage is calculated in mg/kg of body weight, and can be adjusted over the course of the trial based on ADA activity and dAXP concentration as well as on clinical assessment by the treating physician. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | A deficiency in the ADA enzyme results in a build-up of dAXP nucleotides, which are toxic to lymphocytes and lead to impairment of immune function. A detoxified level of dAXP concentration is defined as a trough value of 0.02 millimoles per liter (mmol/L) or lower. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier. | From enrollment to end of treatment up to Month 24 |
| Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | An optimal level of ADA plasma activity is defined as a trough value of 30 millimoles per hour per liter (mmol/h/L) or greater. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier. | From enrollment to end of treatment up to Month 24 |
| Safety of Revcovi | The number of subjects reporting adverse events (AEs). Due to the nature of ADA-SCID, only AEs deemed to be at least possibly related to Revcovi treatment were documented. | From enrollment to end of treatment up to Month 24 |
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Inclusion Criteria:
Male or female, aged newborn to adult
In need of ERT treatment due to one of the following circumstances:
One of the following histories of ERT treatment:
Exclusion Criteria:
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Patients with ADA-SCID who require ERT
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Los Angeles | Los Angeles | California | 90095-1752 | United States | ||
| Allergy & Asthma Medical Group and Research Center, A P.C. |
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Four of the participants had taken part in an earlier trial of Revcovi, study STP-2279-002, and were invited to continue in the registry study. The remaining participants were invited to enroll by their treating physicians.
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| ID | Title | Description |
|---|---|---|
| FG000 | Adagen-naive | Subjects starting on ERT for the first time |
| FG001 | Adagen-transitioning | Subjects switching from Adagen to Revcovi |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 22, 2022 | Sep 4, 2024 |
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| San Diego |
| California |
| 92123 |
| United States |
| UCSF - University of California | San Francisco | California | 94158 | United States |
| Children's National | Washington D.C. | District of Columbia | 20010 | United States |
| University of South Florida Allergy Immunology Clinic | St. Petersburg | Florida | 33701 | United States |
| Childrens Hospital of New Orleans | New Orleans | Louisiana | 70118 | United States |
| Children's Minnesota | Minneapolis | Minnesota | 55404 | United States |
| St. Louis Children's Hospital - Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| UBMD Pediatrics Outpatient Center | Buffalo | New York | 14203 | United States |
| Duke University Hospital | Durham | North Carolina | 27705 | United States |
| Penn State Children's Hospital | Hershey | Pennsylvania | 17033 | United States |
| UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| Le Bonheur Children's Hospital | Memphis | Tennessee | 38105 | United States |
| Seattle Children's | Seattle | Washington | 98101 | United States |
| FG002 | STP-2279-002 Participant | Subjects who had taken part in an earlier Phase III trial of Revcovi |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Adagen-naive | Subjects starting on ERT for the first time |
| BG001 | Adagen-transitioning | Subjects switching from Adagen to Revcovi |
| BG002 | STP-2279-002 Participant | Subjects who had taken part in an earlier Phase III trial of Revcovi |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Number of subjects at or below the toxicity threshold for dAXP concentration | A deficiency in the ADA enzyme results in a build-up of dAXP nucleotides (dAXP), which are toxic to lymphocytes and lead to impairment of immune function. A detoxified level of dAXP concentration is defined as a trough value of 0.02 millimoles per liter (mmol/L) or lower. Since the design of this study included some ADA-SCID patients who had been on an earlier enzyme replacement therapy (Adagen) prior to starting Revcovi and some who were starting it for the first time, it was of importance to see in both cases what the levels of dAXP were at baseline, prior to starting Revcovi. | Count of Participants | Participants |
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| Number of subjects meeting the optimal threshold for ADA activity | An optimal level of ADA plasma activity is defined as a trough value of 30 millimoles per hour per liter (mmol/h/L) or above. Since the design of the study included some patients who had been on an earlier enzyme replacement therapy (Adagen) prior to starting Revcovi and some who were starting it for the first time, it was of importance to see in both cases what ADA levels were at baseline, prior to starting Revcovi. Note: For 6 of the naïve subjects, this measure was obtained after the start of Revcovi, so represents the early effects of treatment rather than actual pre-treatment status. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | A deficiency in the ADA enzyme results in a build-up of dAXP nucleotides, which are toxic to lymphocytes and lead to impairment of immune function. A detoxified level of dAXP concentration is defined as a trough value of 0.02 millimoles per liter (mmol/L) or lower. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier. | The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi. | Posted | Count of Participants | Participants | From enrollment to end of treatment up to Month 24 |
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| Primary | Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | An optimal level of ADA plasma activity is defined as a trough value of 30 millimoles per hour per liter (mmol/h/L) or greater. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier. | The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi. | Posted | Count of Participants | Participants | From enrollment to end of treatment up to Month 24 |
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| Primary | Safety of Revcovi | The number of subjects reporting adverse events (AEs). Due to the nature of ADA-SCID, only AEs deemed to be at least possibly related to Revcovi treatment were documented. | The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi. | Posted | Count of Participants | Participants | From enrollment to end of treatment up to Month 24 |
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At any time during the study. Duration of participation was a minimum of 24 months, or until undergoing successful treatment with stem cell transplant or hematopoietic stem cell gene therapy.
For mortality, all incidences are reported. For non-fatal serious adverse events (SAEs) and non-serious adverse events, due to the nature of the disease, sites were asked to report only those events deemed to be at least possibly related to Revcovi treatment, along with clinically meaningful laboratory abnormalities.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Patients With ADA-SCID in Need of ERT Treatment | All participants will receive Revcovi and will be monitored for adverse events (AEs) throughout their participation in the study. Only AEs deemed at least possibly related to Revcovi treatment will be documented. | 1 | 32 | 0 | 32 | 4 | 32 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 23.1 | Non-systematic Assessment |
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| Exposure via skin contact | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
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| Weight increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
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| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anna Rozova, MD, Clinical Program Leader | Chiesi Canada Corp. | 1-800-854-3534 | 7038 | a.rozova@chiesi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 6, 2023 | Sep 4, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 26, 2021 | Sep 4, 2024 | ICF_002.pdf |
| ID | Term |
|---|---|
| C531816 | Severe combined immunodeficiency due to adenosine deaminase deficiency |
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| ID | Term |
|---|---|
| C000645732 | elapegademase |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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