Adenosine Deaminase DeficiencyDADA2NCT07882680
Expanding the Spectrum of Adenosine Deaminase 2 (ADA2) Deficiency: Towards a Gene Therapy Approach
A study testing bone marrow aspiration and biopsy in people with Adenosine Deaminase Deficiency, run by Istituto Giannina Gaslini at 1 site in Italy.
Trial summary
Adenosine deaminase 2 deficiency (DADA2), caused by autosomal recessive mutations in the ADA2 gene (OMIM: 607575), is an autoinflammatory disease characterized by early-onset inflammatory vasculopathy, stroke, and immunodeficiency (cytopenias and antibody deficiency). Read more about this study
- Who is it for?
- Ages 1 day to 65 years
- Conditions the study is for
- Adenosine Deaminase Deficiency
- What is being tested?
- bone marrow aspiration and biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteItaly
- Study dates
- 31 May 2021to 14 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- DADA2 patients with pure red cell aplasia (PRCA) or other cytopenias (comprehensive assessment).
- DADA2 patients with hypogammaglobulinemia (comprehensive assessment).
- DADA2 patients without overt hematological manifestations (baseline characterization).
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
About this study
Adenosine deaminase 2 deficiency (DADA2), caused by autosomal recessive mutations in the ADA2 gene (OMIM: 607575), is an autoinflammatory disease characterized by early-onset inflammatory vasculopathy, stroke, and immunodeficiency (cytopenias and antibody deficiency). Due to its wide clinical variability and heterogeneous presentation, a large proportion of patients with DADA2 remain undiagnosed.
Anti-TNF therapy is effective in DADA2 patients with inflammatory vasculopathy; however, its long-term efficacy and safety remain unknown.
Read more
We propose to:
- Improve the rate of DADA2 diagnosis in Italy and assess the long-term efficacy and safety of currently available treatments (anti-TNF agents, immunosuppressants, and hematopoietic stem cell transplantation [HSCT]); ii) Further characterize patients with a predominantly hematological phenotype; iii) Develop a gene therapy approach for patients with DADA2, based on the transfer of the functional ADA2 gene into cells.
- Conditions
- Adenosine Deaminase Deficiency
- Being tested
- bone marrow aspiration and biopsy
- Medical subject headings
- Severe combined immunodeficiency due to adenosine deaminase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bone marrow aspiration and biopsyProcedure or surgery
Bone marrow biopsy for morphological examination to quantify overall hematopoietic cellularity, the relative frequencies of individual hematopoietic lineages, lymphocytic infiltration, and fibrosis.dergo bone marrow aspiration and bone marrow biopsy
| Study group | Role | What they receive |
|---|---|---|
| Subjects undergo bone marrow aspiration and bone marrow biopsy. | Experimental | Not described Receives: Procedure: bone marrow aspiration and biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase the number of DADA2 diagnoses
Increase the rate of DADA2 diagnosis through the development of a new enzymatic assay to measure ADA2 activity in dried plasma spots on filter paper and by providing access to molecular testing for patients with suspected DADA2. We will also establish an Italian cohort of patients with DADA2 through the already established Eurofever registry.
Measured: Month 36
Functional and phenotypic characterization of the bone marrow in patients with DADA2 and preclinical studies for gene therapy.
The pathogenesis of hematological manifestations in DADA2 remains largely unknown. Possible mechanisms include an intrinsic defect in ADA2 in bone marrow (BM) progenitor cells or an environmental effect mediated by pro-inflammatory cytokines, as suggested by the strong interferon signature observed in patients with DADA2.
The efficacy of anti-TNF treatment in these patients remains controversial, as both treatment-responsive and treatment-refractory cases have been reported, with some patients requiring hematopoietic stem cell transplantation (HSCT). It is therefore clinically relevant to investigate the potential roles of type I interferon and TNF in the development of hematological manifestations of DADA2 and to determine whether their effects occur at earlier or later stages of bone marrow damage. This could influence therapeutic decision-making by establishing whether early TNF inhibitor treatment provides a clinical benefit or slows the progression of hematological
Measured: Month 36
Develop a Gene Therapy Approach for DADA2
The development of a gene therapy approach for autologous stem cell transplantation may offer a curative treatment for DADA2. Alternative therapeutic strategies are needed to avoid potential transplant-related complications, such as graft-versus-host disease (GVHD) and veno-occlusive disease. There is a strong rationale for developing an approach based on the genetic correction of patients' hematopoietic stem and progenitor cells.
Gene therapy for ADA1 deficiency, a form of severe combined immunodeficiency (SCID), has demonstrated safety and efficacy in clinical trials conducted by Unit 2 . Furthermore, studies conducted by Unit 2 and other research groups have shown that gene therapy based on the ex vivo transduction of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) using lentiviral vectors (LVs) can provide stable, long-term gene expression, even in slowly dividing cells that are difficult to transduce, including long-term repopulating hematopoietic stem ce
Measured: Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2026
- Study start31 May 2021
- Primary completion14 Sep 2025
- Study completion14 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenosine Deaminase DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Giannina Gaslini
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Italy
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07882680
- Sponsor's protocol ID
- DADA2 (11172)
- Acronym
- DADA2
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expanding the Spectrum of Adenosine Deaminase 2 (ADA2) Deficiency: Towards a Gene Therapy Approach
- ClinicalTrials.gov ID
- NCT07882680
- Acronym / sponsor ID
- DADA2 / DADA2 (11172)
- Conditions
- Adenosine Deaminase Deficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Istituto Giannina GasliniUniversity, hospital or other
- Collaborators
- Ministry of Health, Italy
- Study start
- 31 May 2021 (actual)
- Primary completion
- 14 Sep 2025 (actual)
- Study completion
- 14 Sep 2025 (actual)
- First posted
- 20 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adenosine deaminase 2 deficiency (DADA2), caused by autosomal recessive mutations in the ADA2 gene (OMIM: 607575), is an autoinflammatory disease characterized by early-onset inflammatory vasculopathy, stroke, and immunodeficiency (cytopenias and antibody deficiency). Due to its wide clinical variability and heterogeneous presentation, a large proportion of patients with DADA2 remain undiagnosed.
Anti-TNF therapy is effective in DADA2 patients with inflammatory vasculopathy; however, its long-term efficacy and safety remain unknown.
We propose to:
- Improve the rate of DADA2 diagnosis in Italy and assess the long-term efficacy and safety of currently available treatments (anti-TNF agents, immunosuppressants, and hematopoietic stem cell transplantation [HSCT]); ii) Further characterize patients with a predominantly hematological phenotype; iii) Develop a gene therapy approach for patients with DADA2, based on the transfer of the functional ADA2 gene into cells.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects undergo bone marrow aspiration and bone marrow biopsy. | Experimental | Procedure: bone marrow aspiration and biopsy |
Who may qualify
- Ages
- 1 day to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- DADA2 patients with pure red cell aplasia (PRCA) or other cytopenias (comprehensive assessment).
- DADA2 patients with hypogammaglobulinemia (comprehensive assessment).
- DADA2 patients without overt hematological manifestations (baseline characterization).
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bone marrow aspiration and biopsyBone marrow biopsy for morphological examination to quantify overall hematopoietic cellularity, the relative frequencies of individual hematopoietic lineages, lymphocytic infiltration, and fibrosis.dergo bone marrow aspiration and bone marrow biopsy | Procedure or surgery | Subjects undergo bone marrow aspiration and bone marrow biopsy. |
Primary outcome
Increase the number of DADA2 diagnoses
Time frame: Month 36
Increase the rate of DADA2 diagnosis through the development of a new enzymatic assay to measure ADA2 activity in dried plasma spots on filter paper and by providing access to molecular testing for patients with suspected DADA2. We will also establish an Italian cohort of patients with DADA2 through the already established Eurofever registry.
Functional and phenotypic characterization of the bone marrow in patients with DADA2 and preclinical studies for gene therapy.
Time frame: Month 36
The pathogenesis of hematological manifestations in DADA2 remains largely unknown. Possible mechanisms include an intrinsic defect in ADA2 in bone marrow (BM) progenitor cells or an environmental effect mediated by pro-inflammatory cytokines, as suggested by the strong interferon signature observed in patients with DADA2. The efficacy of anti-TNF treatment in these patients remains controversial, as both treatment-responsive and treatment-refractory cases have been reported, with some patients requiring hematopoietic stem cell transplantation (HSCT). It is therefore clinically relevant to investigate the potential roles of type I interferon and TNF in the development of hematological manifestations of DADA2 and to determine whether their effects occur at earlier or later stages of bone marrow damage. This could influence therapeutic decision-making by establishing whether early TNF inhibitor treatment provides a clinical benefit or slows the progression of hematological
Develop a Gene Therapy Approach for DADA2
Time frame: Month 36
The development of a gene therapy approach for autologous stem cell transplantation may offer a curative treatment for DADA2. Alternative therapeutic strategies are needed to avoid potential transplant-related complications, such as graft-versus-host disease (GVHD) and veno-occlusive disease. There is a strong rationale for developing an approach based on the genetic correction of patients' hematopoietic stem and progenitor cells. Gene therapy for ADA1 deficiency, a form of severe combined immunodeficiency (SCID), has demonstrated safety and efficacy in clinical trials conducted by Unit 2 . Furthermore, studies conducted by Unit 2 and other research groups have shown that gene therapy based on the ex vivo transduction of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) using lentiviral vectors (LVs) can provide stable, long-term gene expression, even in slowly dividing cells that are difficult to transduce, including long-term repopulating hematopoietic stem ce
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing bone marrow aspiration and biopsy in people with Adenosine Deaminase Deficiency, run by Istituto Giannina Gaslini at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase the number of DADA2 diagnoses (time frame: Month 36). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.