Adenosine Deaminase Severe Combined Immunodeficiency
Conditions
Keywords
ADA-SCID, Revcovi, ERT
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALelapegademase-lvlr
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.
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
0 Months to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged newborn to adult * In need of ERT treatment due to one of the following circumstances: * Waiting to receive a stem cell transplant * Previously declined, had been found to be ineligible for, or did not respond to a stem cell transplant * Waiting to enrol in a clinical trial on gene therapy, or had been found to be ineligible for or had failed such a trial * One of the following histories of ERT treatment: * Revcovi only * Previously on Adagen but had transitioned to Revcovi * Not yet on any ERT but about to start on Revcovi
Exclusion criteria
* Any condition that, in the opinion of the Investigator, makes the patient unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | From enrollment to end of treatment up to Month 24 | 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. |
| Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | From enrollment to end of treatment up to Month 24 | 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. |
| Safety of Revcovi | From enrollment to end of treatment up to Month 24 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Adagen-naive Subjects starting on ERT for the first time | 7 |
| Adagen-transitioning Subjects switching from Adagen to Revcovi | 21 |
| STP-2279-002 Participant Subjects who had taken part in an earlier Phase III trial of Revcovi | 4 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Adagen-transitioning | STP-2279-002 Participant | Adagen-naive | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 0 Participants | 7 Participants | 18 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 4 Participants | 0 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 2 Participants | 5 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of subjects at or below the toxicity threshold for dAXP concentration | 13 Participants | 4 Participants | 0 Participants | 17 Participants |
| Number of subjects meeting the optimal threshold for ADA activity | 9 Participants | 0 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 4 Participants | 4 Participants | 18 Participants |
| Sex: Female, Male Female | 15 Participants | 2 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 32 |
| other Total, other adverse events | 4 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
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.
Time frame: From enrollment to end of treatment up to Month 24
Population: The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adagen-naive | Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | 7 Participants |
| Adagen-transitioning | Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | 14 Participants |
| STP-2279-002 Participant | Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement | 4 Participants |
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.
Time frame: From enrollment to end of treatment up to Month 24
Population: The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adagen-naive | Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | 6 Participants |
| Adagen-transitioning | Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | 17 Participants |
| STP-2279-002 Participant | Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement | 4 Participants |
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.
Time frame: From enrollment to end of treatment up to Month 24
Population: The As-Treated (AT) population, which included all subjects who received at least one dose of Revcovi.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adagen-naive | Safety of Revcovi | 3 Participants |
| Adagen-transitioning | Safety of Revcovi | 1 Participants |
| STP-2279-002 Participant | Safety of Revcovi | 0 Participants |