Acute Intermittent Porphyria Clinical Trial
Official title:
Phase I, Multicentre, Open Label, Single Dose, Dose-ranging Clinical Trial to Investigate the Safety and Tolerability of a Gene Therapy rAAV2/5-PBGD for the Treatment of Acute Intermittent Porphyria
This is a Phase I trial aimed to determine the safety of the investigational gene therapy
product (rAAV2/5-PBGD) for the treatment of Acute Intermittent Porphyria (AIP).
Up to eight patients fulfilling the eligibility criteria will participate in this
multicentre, open label, single dose, dose-ranging Phase I clinical trial.
The enrolled patients will be followed up to assess the safety profile of the
investigational gene therapy product and to establish the maximum therapeutic safe dose to
be administered in future confirmatory/pivotal clinical trial(s). In addition, the
biological and clinical response to the treatment with rAAV2/5-PBGD in AIP patients will be
assessed.
A complete evaluation of the clinical (symptoms and quality of life assessment) and
laboratory (blood and urine) data will be performed.
Status | Completed |
Enrollment | 8 |
Est. completion date | November 2014 |
Est. primary completion date | July 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 64 Years |
Eligibility |
Inclusion Criteria: - Patient's written Informed Consent - Age between 18 and 64 years, inclusively. - Patients with confirmed diagnosis of Acute Intermittent Porphyria(AIP), as confirmed by clinical, biochemical data and genetic confirmation of porphobilinogen deaminase (PBGD) gene mutation. The patient must have a severe AIP condition, with at least two hospitalizations during the previous year due to acute attacks (clinical manifestations of acute porphyria), or at least four hospitalizations during the previous year due to the requirement of hospital treatment administration (including day-hospital and home hospital program) - Previous participation in the "Observational study of acute intermittent porphyria patients" for at least six months. - Ability to follow instructions and cooperate during the study conduct Exclusion Criteria: - Pregnant women, as confirmed by a positive urine pregnancy test, or with intention of becoming pregnant - Female subjects of childbearing potential who are not using barrier methods of contraception, at least during the study. - Male subjects with partners of child bearing potential who are not using barrier contraceptive methods, at least during the study - Acute or chronic liver disease of viral, autoimmune or metabolic causes - History of acute or chronic severe gastrointestinal dysfunction (different than those typical gastrointestinal symptoms associated with an acute attack of AIP), in the opinion of the principal investigator - Kidney disorder (renal impairment defined as plasma creatinine > 2 mg/dl (150 µmol/l)), severe respiratory disease, severe autoimmune disease or severe acute active infection - Evidence of active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection as reflected by HBs antigen or HCV-antibodies positivity (in case of HCV-antibodies positivity a HCV-RNA test should be performed in order to confirm active viral replication) - Positive human immunodeficiency virus (HIV) serological test - History of drug use (cannabis, cocaine, amphetamines, barbiturates) or alcohol abuse or addiction, during the three months preceding the selection visit - Presence of neutralizing antibodies against adeno-associated serotype 5 (AAV5) - Current or previous (within the previous 12 months) participation in a gene therapy trial. - Previous participation (at any time) in a gene therapy trial using AAV vectors - Any other disease or condition that, in the opinion of the principal investigator, contraindicates the participation in the study because it can expose the patient to a risk or because it disqualifies the patient to complete the schedule of the study. |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Spain | 12 Octubre Hospital | Madrid | |
Spain | Clinica Universidad de Navarra | Pamplona | Navarra |
Lead Sponsor | Collaborator |
---|---|
Digna Biotech S.L. | Nationales Centrum für Tumorerkrankungen, Porphyria Centre Sweden, UniQure N.V., University of Navarra |
Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of patients with Adverse Events and Serious Adverse Events | To assess the safety and determine the maximum therapeutic safe dose of the investigational gene therapy (GT) product rAAV2/5-PBGD for the treatment of AIP, registering and evaluating the occurrence of Adverse Events and/or Serious Adverse Events at the dose identified will be performed | Up to 48 weeks | Yes |
Secondary | Effect of the treatment on porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary level. | Up to 48 weeks | No | |
Secondary | Clinical evolution of acute intermittent porphyria. Frequency of hospitalizations | Up to 48 weeks | No | |
Secondary | Frequency of treatments for AIP symptoms | The information regarding the requirement of specific treatments for symptoms control (analgesics, hemin and glucose endovenous solutions) will be collected. | Up to 48 weeks | No |
Secondary | Psychological evaluation of AIP patients | Anxiety and depression will be assessed by using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) rating scales. | Up to 48 weeks | No |
Secondary | Health related quality of life of AIP patients | Health-related quality of life will be assessed through the SF-36v2 questionnaire | Up to 48 weeks | No |
Secondary | Frequency of AIP symptoms | Up to 48 weeks | No | |
Secondary | Pharmacokinetic parameters | Selection visit, Days 1, 2 and 3, week 1, week 2, week 3 and week 4 | No |
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