Leukocyte Adhesion Defect - Type IPhase 1/2NCT03812263
A Clinical Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I
A Phase 1/2 study testing RP-L201 in people with Leukocyte Adhesion Defect - Type I, run by Rocket Pharmaceuticals Inc. at 3 sites in 3 countries.
Trial summary
The primary purpose of the Phase I portion of the study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with the therapeutic lentiviral vector, Chim-CD18-WPRE, RP-L201. Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Leukocyte Adhesion Defect - Type I
- What is being tested?
- RP-L201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 30 Aug 2019to 12 Sep 2023
- Phase
- Phase 1/2
- 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 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on <2% neutrophils (polymorphonuclear neutrophils (PMNs)). Subjects in which CD18+ PMNs are >2% will be considered eligible with <2% CD11a or CD11b expressing PMNs and if there is a documented ITGB2 mutation and clinical history consistent with LAD-I (or known family history).
- At least one (1) prior significant bacterial or fungal infection US NCI CTCAE, v5.0, Grade ≥2). This criterion is not required for subjects with documented family history who meet the above inclusion criteria.
- Age ≥3 months.
- Considered to be an appropriate candidate for autologous transplantation of hematopoietic stem cells.
- A competent custodial parent with legal capacity to execute an institutional review board (IRB)/ethics committee (EC)-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/EC and with local requirements).
- Ability to comply with trial procedures including investigational therapy and follow-up evaluations.
Who cannot join
- Availability of a medically-eligible human leukocyte antigen (HLA)-identical sibling donor transplant. Subjects may not be included in this trial as an alternative to a clinically-indicated and feasible HLA-matched sibling donor hematopoietic stem cell transplant. If an HLA-identical sibling is identified, but mobilized peripheral blood or bone marrow hematopoietic stem cell collection is not feasible (for example: donor is in utero, is a newborn from whom cord blood was not collected, or is unable to undergo donation procedure because of medical impairments), then inclusion may be permitted per Investigator discretion.
- Hepatic dysfunction as defined by either:
- Bilirubin >1.5× the upper limit of normal (ULN) or
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5×ULN.
- Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or the requirement for either peritoneal dialysis or hemodialysis.
- Pulmonary dysfunction as defined by either:
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- Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection).
- Oxygen saturation (by pulse oximetry) <90%.
- Evidence of active metastatic or locoregionally advanced malignancy (including hematologic malignancy) for which survival is anticipated to be less than 3 years.
- Serious infections with persistent bloodstream pathogens at time of trial entry. (Subjects with active infections (e.g., unresolved ulcerative lesions, skin or oral infections) are permitted as long as appropriate antibiotic therapy has been (or is being) administered).
- Any medical or other contraindication for both leukapheresis and bone marrow harvest procedure, as determined by the treating Investigator.
- Any medical or other contraindication for the administration of conditioning therapy, as determined by the treating Investigator.
- Significant medical conditions, including documented human immunodeficiency virus (HIV) infection, poorly-controlled diabetes, poorly-controlled hypertension, poorly-controlled cardiac arrhythmia or congestive heart failure; or arterial thromboembolic events (including stroke or myocardial infarction) within the 6 prior months.
- Any medical or psychiatric condition that in the opinion of the Investigator renders the subject unfit for trial participation or at higher than acceptable risk for participation.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095-1489
United Kingdom1 site
University College London Great Ormond Street Institute of Child Health
London
About this study
Official title: Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector Encoding the ITGB2 Gene
The primary purpose of the Phase I portion of the study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with the therapeutic lentiviral vector, Chim-CD18-WPRE, RP-L201. The primary objectives of the Phase II portion of the study are evaluation of survival, as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post-infusion without allogeneic hematopoietic stem cell transplant (HSCT) and characterization of the safety and toxicity associated with the infusion.
Read the detailed description
This is a pediatric non-randomized open-label Phase I/II clinical trial. The Phase I portion will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the ITGB2 gene in subjects with severe LAD-I. CD34+ cells will be transduced ex vivo with the therapeutic vector followed by cryopreservation. If the number of CD34+ cells that are available for infusion is at least 2x10e6 total CD34+ cells/kg, subjects will undergo myeloablative conditioning with intravenous busulfan. Subjects will then receive infusion of gene-corrected hematopoietic cells approximately 24 hours following the final busulfan dose.
The active agent is a self-inactivating lentiviral vector carrying the therapeutic ITGB2 gene, encoding for the human CD18 receptor (β2 integrin subunit). The therapeutic product is the subject's autologous hematopoietic stem cells that have been transduced with the lentiviral vector.
- Conditions
- Leukocyte Adhesion Defect - Type I
- Being tested
- RP-L201
- Keywords
- Leukocyte Adhesion Deficiency- Type I, LAD-I, ITGB2 mutation, CD18 deficiency
- Medical subject headings
- Leukocyte adhesion deficiency type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-L201Biological
CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE.
| Study group | Role | What they receive |
|---|---|---|
| RP-L201 | Experimental | RP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single intravenous infusion Receives: Biological: RP-L201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
Evaluation of safety associated with treatment with RP-L201
Measured: 2 years
Phase II: Survival following infusion of RP-L201
, as determined by the proportion of subjects alive at least 1-year post investigational product infusion without allogeneic HSCT and alive at age 2 (24 months) without allogeneic HSCT for subjects less than 1 year of age at study enrollment.
Measured: 2 years
Phase II: Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
Evaluation of safety associated with treatment with RP-L201
Measured: 2 years
Secondary outcomes (7)
CD18 expression after infusion of RP-L201
Determination of the percentage of subjects in whom infusion of RP-L201 results in a change in the percentage of neutrophils expressing CD18 to at least 10%
Measured: 2 years
Genetic correction after infusion of RP-L201
Determination of the percentage of subjects in whom infusion of RP-L201 results in at least 10% of peripheral blood neutrophils carrying the therapeutic Chim-CD18-WPRE lentiviral vector provirus at 6 months post-infusion
Measured: 2 years
Incidence of infections after infusion of RP-L201
Determination of the incidence of significant infections, infection-related hospitalizations, and prolonged infection-related hospitalizations, comparing the incidences prior to investigational product infusion and subsequent to hematopoietic reconstitution.
Measured: 2 years
Assessment of LAD-I-associated neutrophilia after infusion of RP-L201
Evaluation of change to partially normal or to normal levels of LAD-I-associated neutrophilia
Measured: 2 years
Assessment of LAD-I-associated leukocytosis after infusion of RP-L201
Evaluation of change to partially normal or to normal levels of LAD-I-associated leukocytosis
Measured: 2 years
Assessment of skin rash or periodontal abnormalities after infusion of RP-L201
Evaluation of resolution (partial or complete) of any underlying skin rash or periodontal abnormalities
Measured: 2 years
Assessment of overall survival after infusion of RP-L201
Assessment of event-free survival (EFS) defined as survival without graft failure (GF) and without acute graft-versus-host disease (aGVHD) grade 2 to 4.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2019
- Study start30 Aug 2019
- Primary completion12 Sep 2023
- Study completion12 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukocyte Adhesion Defect - Type IStudies of the same condition, open and under way.
- More trials run by Rocket Pharmaceuticals Inc.The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Donald B Kohn, MD, Principal investigator, University of California, Los AngelesClaire Booth, MBBS, PhD, MSc, Principal investigator, University College London Great Ormond Street Institute of Child HealthJulián Sevilla Navarro, MD, PhD, Principal investigator, Hospital Infantil Universitario Niño Jesús
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03812263
- Sponsor's protocol ID
- RP-L201-0318
- Status last verified
- Nov 2023
- First submitted
- 18 Jan 2019
- Last updated
- 15 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Booth C, Sevilla J, Almarza E, Kuo CY, Zubicaray J, Terrazas D, O'Toole G, Chitty-Lopez M, Choi G, Nicoletti E, Long-Boyle J, Fernandes A, Chetty K, De Oliveira S, Banuelos C, Xu-Bayford J, Bastone AL, John-Neek P, Jackson C, Moore TB, Gilmour K, Schambach A, Rothe M, Kasbekar S, Rao GR, Patel K, Shah G, Thrasher AJ, Bueren JA, Schwartz JD, Kohn DB. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2025 May 1;392(17):1698-1709. doi: 10.1056/NEJMoa2407376.
PubMed 40305711
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector Encoding the ITGB2 Gene
- ClinicalTrials.gov ID
- NCT03812263
- Acronym / sponsor ID
- RP-L201-0318
- Conditions
- Leukocyte Adhesion Defect - Type I
- Keywords
- Leukocyte Adhesion Deficiency- Type I, LAD-I, ITGB2 mutation, CD18 deficiency
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Study start
- 30 Aug 2019 (actual)
- Primary completion
- 12 Sep 2023 (actual)
- Study completion
- 12 Sep 2023 (actual)
- First posted
- 23 Jan 2019 (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.
The primary purpose of the Phase I portion of the study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with the therapeutic lentiviral vector, Chim-CD18-WPRE, RP-L201. The primary objectives of the Phase II portion of the study are evaluation of survival, as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post-infusion without allogeneic hematopoietic stem cell transplant (HSCT) and characterization of the safety and toxicity associated with the infusion.
Detailed description
This is a pediatric non-randomized open-label Phase I/II clinical trial. The Phase I portion will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the ITGB2 gene in subjects with severe LAD-I. CD34+ cells will be transduced ex vivo with the therapeutic vector followed by cryopreservation. If the number of CD34+ cells that are available for infusion is at least 2x10e6 total CD34+ cells/kg, subjects will undergo myeloablative conditioning with intravenous busulfan. Subjects will then receive infusion of gene-corrected hematopoietic cells approximately 24 hours following the final busulfan dose.
The active agent is a self-inactivating lentiviral vector carrying the therapeutic ITGB2 gene, encoding for the human CD18 receptor (β2 integrin subunit). The therapeutic product is the subject's autologous hematopoietic stem cells that have been transduced with the lentiviral vector.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP-L201 | Experimental | Biological: RP-L201RP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single intravenous infusion |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on <2% neutrophils (polymorphonuclear neutrophils (PMNs)). Subjects in which CD18+ PMNs are >2% will be considered eligible with <2% CD11a or CD11b expressing PMNs and if there is a documented ITGB2 mutation and clinical history consistent with LAD-I (or known family history).
- At least one (1) prior significant bacterial or fungal infection US NCI CTCAE, v5.0, Grade ≥2). This criterion is not required for subjects with documented family history who meet the above inclusion criteria.
- Age ≥3 months.
- Considered to be an appropriate candidate for autologous transplantation of hematopoietic stem cells.
- A competent custodial parent with legal capacity to execute an institutional review board (IRB)/ethics committee (EC)-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/EC and with local requirements).
Key exclusion criteria (14 listed)
- Availability of a medically-eligible human leukocyte antigen (HLA)-identical sibling donor transplant. Subjects may not be included in this trial as an alternative to a clinically-indicated and feasible HLA-matched sibling donor hematopoietic stem cell transplant. If an HLA-identical sibling is identified, but mobilized peripheral blood or bone marrow hematopoietic stem cell collection is not feasible (for example: donor is in utero, is a newborn from whom cord blood was not collected, or is unable to undergo donation procedure because of medical impairments), then inclusion may be permitted per Investigator discretion.
- Hepatic dysfunction as defined by either:
- Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or the requirement for either peritoneal dialysis or hemodialysis.
- Pulmonary dysfunction as defined by either:
- Evidence of active metastatic or locoregionally advanced malignancy (including hematologic malignancy) for which survival is anticipated to be less than 3 years.
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 |
|---|---|---|
| RP-L201CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE. | Biological | RP-L201 |
Primary outcome
Phase I: Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
Time frame: 2 years
Evaluation of safety associated with treatment with RP-L201
Phase II: Survival following infusion of RP-L201
Time frame: 2 years
, as determined by the proportion of subjects alive at least 1-year post investigational product infusion without allogeneic HSCT and alive at age 2 (24 months) without allogeneic HSCT for subjects less than 1 year of age at study enrollment.
Phase II: Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
Time frame: 2 years
Evaluation of safety associated with treatment with RP-L201
7 secondary outcomes
CD18 expression after infusion of RP-L201
Time frame: 2 years
Genetic correction after infusion of RP-L201
Time frame: 2 years
Incidence of infections after infusion of RP-L201
Time frame: 2 years
Assessment of LAD-I-associated neutrophilia after infusion of RP-L201
Time frame: 2 years
Assessment of LAD-I-associated leukocytosis after infusion of RP-L201
Time frame: 2 years
Assessment of skin rash or periodontal abnormalities after infusion of RP-L201
Time frame: 2 years
Assessment of overall survival after infusion of RP-L201
Time frame: 2 years
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 15 Nov 2023.
- Derived from this study: PubMed 40305711Booth C, Sevilla J, Almarza E, Kuo CY, Zubicaray J, Terrazas D, O'Toole G, Chitty-Lopez M, Choi G, Nicoletti E, Long-Boyle J, Fernandes A, Chetty K, De Oliveira S, Banuelos C, Xu-Bayford J, Bastone AL, John-Neek P, Jackson C, Moore TB, Gilmour K, Schambach A, Rothe M, Kasbekar S, Rao GR, Patel K, Shah G, Thrasher AJ, Bueren JA, Schwartz JD, Kohn DB. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2025 May 1;392(17):1698-1709. doi: 10.1056/NEJMoa2407376.
- 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.
Donald B Kohn, MD principal investigator
University of California, Los Angeles
Claire Booth, MBBS, PhD, MSc principal investigator
University College London Great Ormond Street Institute of Child Health
Julián Sevilla Navarro, MD, PhD principal investigator
Hospital Infantil Universitario Niño Jesús
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RP-L201 in people with Leukocyte Adhesion Defect - Type I, run by Rocket Pharmaceuticals Inc. at 3 sites in 3 countries.
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 6 inclusion and 14 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 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Spain, United Kingdom. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Phase I: Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 (time frame: 2 years). 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?
On the ClinicalTrials.gov record for NCT03812263, which also lists 1 linked publication.
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 15 Nov 2023.