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Leukocyte Adhesion Defect - Type IPhase 1NCT03825783

A Gene Therapy Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I

A Phase 1 study testing RP-L201 in people with Leukocyte Adhesion Defect - Type I, run by Rocket Pharmaceuticals Inc. at 1 site in Spain.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The primary purpose of the Phase I portion of the study is to determine the safety profile and preliminary evidence of efficacy associated with infusion of autologous gene-corrected hematopoietic stem cells. 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
0 participants
Where
1 siteSpain
Study dates
15 Apr 2019to Oct 2021
Phase
Phase 1
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]). (Patients 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 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], v5.0, Grade ≥2). This criteria is not required for patients with documented family history who meet the above inclusion criteria.
  • Age ≥3 months.
  • Considered to be an appropriate candidate for autologous transplantation of HSCs.
  • A competent custodial parent with legal capacity to execute an Ethics Committee (EC)-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable patients, in accordance with the directive of the 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. Patients may not be included in this trial as an alternative to a clinically-indicated and feasible HLA-matched sibling donor HSC transplant. If an HLA-identical sibling is identified, but mobilized peripheral blood or bone marrow HSC 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 the Principal 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
  • Pulmonary dysfunction as defined by either:
  • Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection).
Show all 14Show fewer
  • 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. (Patients 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 leukopheresis 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 Principal Investigator renders the patient unfit for trial participation or at higher than acceptable risk for participation.
  • Patients who are evaluated for the trial and determined ineligible may be subsequently evaluated and declared eligible if the criteria by which they were considered ineligible is reversible (for example: bloodstream infection, transient increase in liver enzymes) and there is documented and plausible evidence of its resolution in the opinion of the Principal Investigator.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Infantil Universitario Niño Jesús (HIUNJ)

    Madrid, 28009

Other trials in Spain

About this study

Official title: Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I 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 determine the safety profile and preliminary evidence of efficacy associated with infusion of autologous gene-corrected hematopoietic stem cells.

Read the detailed description

The study is a pediatric non-randomized open-label Phase I clinical trial. This 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 Leukocyte Adhesion Deficiency-I (LAD-I). Subjects will undergo mobilization and collection of peripheral blood hematopoietic stem cells (HSCs) with granulocyte-colony stimulating factor (G-CSF) and plerixafor or bone marrow harvest in select circumstances.

HSCs will then be transduced with the therapeutic vector (Chim.hCD18-LV), with the intent of enabling stable integration of the provirus in the genome of stem and progenitor cells.

If the number of CD34+ cells that are cryopreserved is at least 4×10E6 total CD34+ cells/kg, subjects will receive myeloablative conditioning with intravenous busulfan. The gene-modified CD34+ cells will be then transplanted back into the subject.

Once engrafted, it is anticipated that the gene-modified stem and progenitor cells will enable hematopoiesis, generating blood cells in which the integrated therapeutic gene (ITGB2) will be transcribed and translated to produce the therapeutic CD18 protein with a preferential high expression in mature myeloid cells. Leukocytes expressing a functional CD18 will have the capability to arrest on endothelial surfaces and extravasate to infectious sites, enabling a competent antimicrobial response and reversing the clinical disorder.

Being tested
RP-L201
Keywords
Leukocyte Adhesion Deficiency- Type I, LAD-I
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 groups in NCT03825783
Study groupRoleWhat they receive
RP-L201ExperimentalRP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single infusion in subjects with severe LAD-I
Receives: Biological: RP-L201

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

  2. Survival following infusion of RP-L201

    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

    Measured: 2 years

Secondary outcomes (6)

  1. 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% in 2 years

    Measured: 2 years

  2. Genetic correction after infusion of RP-L201

    Determination of whether infusion of RP-L201 results in vector copy number/cell of at least 0.1 in peripheral blood neutrophils carrying the therapeutic Chim.hCD18-LV provirus at 6 months post-infusion

    Measured: 6 months

  3. Incidence of infections after infusion of RP-L201

    Determination of the incidence and severity of bacterial or other infections (subsequent to hematopoietic reconstitution)

    Measured: 2 years

  4. Assessment of number of participants with a change in 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

  5. Assessment of number of participants with a change in skin lesions or periodontal abnormalities after infusion of RP-L201

    Evaluation of resolution (partial or complete) of any underlying skin lesions or periodontal abnormalities

    Measured: 2 years

  6. Assessment of overall survival after infusion of RP-L201

    Evaluation of overall survival (beyond age 2 years and beyond the initial year subsequent to investigational therapy)

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2019
  2. Study start15 Apr 2019
  3. Primary completionOct 2021 (estimated)
  4. Study completionOct 2021 (estimated)

Why it stopped: Patients were enrolled under global Phase 1/2 protocol RP-L201-0318.

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03825783
Sponsor's protocol ID
RP-L201-0218
Status last verified
Nov 2021
First submitted
25 Jan 2019
Last updated
7 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RP-L201 in people with Leukocyte Adhesion Defect - Type I, run by Rocket Pharmaceuticals Inc. at 1 site in Spain.

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: withdrawn, as of the sponsor's last update on 7 Dec 2021. 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 Spain. 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 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.

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 was withdrawn before enrolling participants, so there are no results.

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?

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 2 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 NCT03825783.

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 7 Dec 2021.

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