A Phase I/II Gene Therapy trial for X-CGD with a SIN gamma retroviral vector

Phase 1

• Conditions: Chronic granulomatous disease (CGD) is a congenital immunodeficiency, in which neutrophil granulocytes and monocytes are not capable of producing reactive oxygen species and therefore are unable to kill phagocytized bacteria or fungi.; MedDRA version: 14.1Level: PTClassification code 10008906Term: Chronic granulomatous diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-001725-26-DE
• Lead Sponsor: Johann Wolfgang Goethe-University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-12-18
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

1.Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by DHR- and NBT-assay.
2.History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures.
3.18 years old or older
4.No HLA identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months.
5.Normal organ-function: GFR = 60ml/min., Bilirubin = 1,5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, PTT 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes > 3 x 109/l, Granulocytes > 1.5 x 109/l, Thrombocytes >100 x 109/l

6.Contraception from start of G-CF application until 1 year after retransfusion of the gene-corrected cells.
Women with childbearing potential or partners with childebearing potential of male patients with have to apply safe contraceptive measures (Pearlindex <1%), as sexual abstinence, combination of an oral contraceptive, IUS, vaginal ring with drug delivery, contraceptive pad, implanted contraceptive, injected depot-contraceptive; in combination with a second contraceptive method, in terms os a barrier-method, such as condom, diaphragm /cervical cap with spermicide or sterilization in male patients or partners.
a.A woman of childbearing potential is defined, as sexually mature woman without hysterectomy or surgical sterilization, who has not been postmenopausal for at least 12 months (no menstruation within the last 12 months).
7.No interferon-gamma injection within two weeks prior to hematopoietic stem cell mobilization
8.Karnofsky-Index > 70%
9.Signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients with non-controlled acute infections
2.Severe cardiac or pulmonary malfuctions: ejection fraction < 60%, valvular heart disease > II°, arrhythmia requiring therapy, FEV1/VC < 75% , DLCO <60%
3.Bilirubin > 1,5-fold upper reference-level
4.Creatinine-clearance <60ml/min

5.HIV-, Hepatitis B- or C - infection

6.Contraindications for G-CSF administration, as autoimmune vasculitis.
7.Contraindications for stem cell apheresis, as low hemoglobin <8g/dl, cardiovascular instability or severe coagulapathy
8.Pregnacy or breast-feeding
9.Drug- or alcohol-abuse
10. Lack of search for an unrelated donor
11. Patients with an available HLA 9/10 MMUD will be excluded from the study if SCT is considered to be beneficial according to thorough risk-benefit-assessment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified