NEWS HIGHLIGHTS
Published Studies Related to Adagen (Pegademase)
Pegademase bovine: replacement therapy for severe combined immunodeficiency disease. [1991.10]
Severe combined immunodeficiency (SCID) represents a syndrome characterized by abnormal function of cellular and humoral immunity. Of the various types of SCID, approximately one-fourth are associated with adenosine deaminase (ADA) deficiency...
Clinical Trials Related to Adagen (Pegademase)
MND-ADA Transduction of CD34+ Cells From Children With Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID) [Recruiting]
Severe combined immune deficiency (SCID) may result from inherited deficiency of the enzyme
adenosine deaminase (ADA). Children with ADA-deficient SCID often die from infections in
infancy, unless treated with either a bone marrow transplant or with ongoing injections of
PEG-ADA (Adagen) enzyme replacement therapy. Successful BMT requires the availability of a
matched sibling donor for greatest success, and treatment using bone marrow from a less-well
matched donor may have a higher rate of complications. PEG-ADA may restore and sustain
immunity for many years, but is very expensive and requires injections 1-2 times per week on
an ongoing basis. This clinical trial is evaluating the efficacy and safety of an
alternative approach, by adding a normal copy of the human ADA gene into stem cells from the
bone marrow of patients with ADA-deficient SCID. Eligible patients with ADA-deficient SCID,
lacking a matched sibling donor, will be eligible if they meet entry criteria for adequate
organ function and absence of active infections and following the informed consent process.
Bone marrow will be collected from the back of the pelvis from the patients and processed in
the laboratory to isolate the stem cells and add the human ADA gene using a retroviral
vector. The patients will receive a moderate dosage of busulfan, a chemotherapy agent that
eliminates some of the bone marrow stem cells in the patient, to "make space" for the
gene-corrected stem cells to grow once they are given back by IV. Patients will be followed
for two years to assess the potentially beneficial effects of the procedure on the function
of their immune system and to assess possible side-effects. This gene transfer approach may
provide a better and safer alternative for treatment of patients with ADA-deficient SCID.
Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study [Completed]
This study will monitor the long-term effects of gene therapy in patients with severe
combined immunodeficiency disease (SCID) due to a deficiency in an enzyme called adenosine
deaminase (ADA). It will also follow the course of disease in children who are not receiving
gene therapy, but may have received enzyme replacement therapy with the drug PEG-ADA.
ADA is essential for the growth and proper functioning of infection-fighting white blood
cells called T and B lymphocytes. Patients who lack this enzyme are, therefore, immune
deficient and vulnerable to frequent infections. Injections of PEG-ADA may increase the
number of immune cells and reduce infections, but this enzyme replacement therapy is not a
definitive cure. In addition, patients may become resistant or allergic to the drug. Gene
therapy, in which a normal ADA gene is inserted into the patient's cells, attempts to
correcting the underlying cause of disease.
Patients with SCID due to ADA deficiency may be eligible for this study. Patients may or may
not have received enzyme replacement therapy or gene transfer therapy, or both. Participants
will have follow-up visits at the National Institutes of Health in Bethesda, Maryland, at
least once a year for a physical examination, blood tests, and possibly the following
additional procedures to evaluate immune function:
1. Bone marrow sampling - A small amount of marrow from the hip bone is drawn (aspirated)
through a needle. The procedure can be done under local anesthesia or light sedation.
2. Injection of small amounts of fluids into the arm to study if the patient's lymphocytes
respond normally.
3. Administration of vaccination shots.
4. Collection of white blood cells through apheresis - Whole blood is collected through a
needle placed in an arm vein. The blood circulates through a machine that separates it
into its components. The white cells are then removed, and the red cells, platelets and
plasma are returned to the body, either through the same needle used to draw the blood
or through a second needle placed in the other arm.
5. Blood drawings to obtain and study the patient's lymphocytes.
EZN-2279 in Patients With ADA-SCID [Not yet recruiting]
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of
EZN-2279 in patients with ADA-deficient combined immunodeficiency currently being treated
with Adagen.
Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency [Recruiting]
This study will evaluate a new method for delivering gene transfer therapy to patients with
severe combined immunodeficiency disease (SCID) due to a defective adenosine deaminase (ADA)
gene. This gene codes for the adenosine deaminase enzyme, which is essential for the proper
growth and function of infection-fighting white blood cells called T and B lymphocytes.
Patients who lack this enzyme are vulnerable to frequent and severe infections.
Some patients with this disease receive enzyme replacement therapy with weekly injections of
the drug PEG-ADA (ADAGEN). This drug may increase the number of immune cells and reduce
infections, but it is not a cure. Gene transfer therapy, in which a normal ADA gene is
inserted into the patient's cells, attempts to correct the underlying cause of disease.
This therapy has been tried in a small number of patients with varying degrees of success.
In this study, the gene will be inserted into the patient's stem cells (cells produced by
the bone marrow that mature into the different blood components-white cells, red cells and
platelets).
Patients with ADA deficiency and SCID who are taking PEG-ADA and are not candidates for
HLA-identical sibling donor bone marrow transplantation may be eligible for this study.
Participants will be admitted to the NIH Clinical Center for 2 to 3 days. Stem cells will
be collected either from cord blood (in newborn patients) or from the bone marrow. The bone
marrow procedure is done under light sedation or general anesthesia. It involves drawing a
small amount of marrow through a needle inserted into the hip bone. The stem cells in the
marrow will be grown in the laboratory and a normal human ADA gene will be transferred into
them through a special type of disabled mouse virus. A few days later, the patient will
receive the ADA-corrected cells through an infusion in the vein that will last from 10
minutes to 2 hours.
Patients will be evaluated periodically for immune function with blood tests, skin tests,
and reactions to tetanus, diphtheria, H. influenza B and S. pneumoniae vaccinations. The
survival of ADA-corrected cells will be monitored through blood tests. The number and
amount of blood tests will depend on the patient's age, weight and health, but is expected
that blood will not be drawn more than twice a month. Patients will also undergo bone
marrow biopsy aspirate (as described above) twice a year. Patients will be followed once a
year indefinitely to evaluate the long-term effects of therapy.
Patients Treated for SCID (1968-2010) [Recruiting]
People with Primary Immune Deficiency (PID) may develop severe, life-threatening infections
as a result of inherited defects in the genes that normally instruct blood-forming cells to
develop and to fight infections. PID diseases include Severe Combined Immune Deficiency
(SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated
by transplantation of bone marrow stem cells from a healthy person or, in some cases, by
enzyme replacement or by gene therapy. Patients with SCID were among the first to receive
bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40
years ago, and HCT is the standard treatment today for this group of diseases. Since PID
diseases are rare, there are not enough patients at any single center to determine the full
range of causes, natural history, or best methods of treatment. For this research study many
PID centers across North America have organized into the Primary Immune Deficiency Treatment
Consortium (PIDTC) to pool their experience and study PIDs together. Researchers will
collect information on your general health, psychological and developmental health, and the
current status of your immune system to help better define future approaches to PID
treatments.
Reports of Suspected Adagen (Pegademase) Side Effects
Autoimmune Thrombocytopenia (3),
Lung Infection Pseudomonal (2),
Therapeutic Response Decreased (2),
Skin Papilloma (2),
Urticaria (1),
Idiopathic Thrombocytopenic Purpura (1),
Peritoneal Haemorrhage (1),
Anti-Platelet Antibody Positive (1),
Pulmonary Alveolar Haemorrhage (1)
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