Observational Study of Acute Intermittent Porphyria Patients

Brief Title

Observational Study of Acute Intermittent Porphyria Patients

Official Title

Observational Study of Acute Intermittent Porphyria Patients

Brief Summary

      This is an observational prospective study that will allow evaluating the clinical and
      laboratory parameters evolution of at least eight patients with AIP.

      This study will allow establishing a baseline for the evaluation of the eight patients that
      are planned to be included in a gene therapy clinical trial (AAVPBGD-AIP-001) for the AIP
      treatment using a rAAV5-AAT-cohPBGD expression.

      Patients fulfilling the study inclusion criteria will undergo a clinical and laboratory
      evaluation for a minimum of 6 months (with one inclusion visit, one final visit and at least
      two visits of follow up) up to a maximum of 24 months until their inclusion in the subsequent
      clinical trial.

      A complete evaluation of the clinical (symptoms and quality of life assessment) and
      laboratory (blood and urine) data will be collected.
    

Detailed Description

      Acute Intermittent Porphyria (AIP) is inherited as an autosomal dominant disorder of the heme
      biosynthesis pathway. AIP is caused by a genetic defect in porphobilinogen deaminase (PBGD) a
      key enzyme for heme synthesis.

      AIP is characterized by acute episodes and asymptomatic periods. Neuropathic symptoms are
      predominantly in these attacks, which may be related to the toxic effect produced by the
      precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), accumulated because the
      enzyme deficiency. It occurs with very low prevalence (1 in 50,000), but figures for
      prevalence based on clinical manifestations (i.e., acute attacks) greatly underestimate the
      number of patients with latent AIP.

      Abdominal pain is the most common symptom, sometimes with constipation. Paraesthesias and
      paralysis also occur, and death may result from respiratory paralysis. Many other phenomena,
      including seizures, psychotic episodes, and hypertension, develop during acute attacks
      (Kadish 1999, Anderson 2007). Acute attacks rarely occur before puberty. They may be
      precipitated by porphyrogenic drugs such as barbiturates, progestogens and sulfonamides, some
      of which are known to induce the first rate-controlling step in heme synthesis, ALA
      synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes;
      attacks are more common in women.

      This is a pre-treatment observational study designed to collect clinical and laboratory data
      to later compare baseline and post-treatment variables in a future clinical trial
      (AAVPBGD-AIP-001) for the AIP treatment using a recombinant adeno-associated virus vector
      with a liver-specific promoter for the PBGD expression (rAAV5-AAT-cohPBGD).

      The PRIMARY OBJECTIVE is to observe the changes of PBG and ALA urinary levels in AIP
      patients.

      The SECONDARY OBJECTIVES are:

        -  To observe and document the frequency of acute attacks, the nature and frequency of
           symptoms, medication and hospitalization requirements, neurological involvement,
           psychological involvement and health-related quality of life of AIP patients.

        -  To record the use of concomitant medication in AIP patients.

      At least eight patients fulfilling the inclusion/exclusion criteria will be included. No
      sample size assessments have been taken into account due to the study nature, so this number
      of patients is considered sufficient to meet the study objectives.
    


Study Type

Observational


Primary Outcome

Changes of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary levels in AIP patients

Secondary Outcome

 Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations

Condition

Acute Intermittent Porphyria


Study Arms / Comparison Groups

 Acute intermittent porphyria
Description:  Patient diagnosed of AIP (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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

9

Start Date

August 2011

Completion Date

February 2014

Primary Completion Date

July 2013

Eligibility Criteria

        Inclusion Criteria:

          -  Patient's written consent to take part in the study after receiving all the
             information regarding the design, objectives and potential risks that may arise during
             the observational study; as well as general information about the subsequent clinical
             trial.

          -  Age between 18 and 65 years, inclusively.

          -  Patient diagnosed of AIP (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).

          -  Ability to follow instructions and cooperate during the study conduct.

        Exclusion Criteria:

          -  Pregnant women, positive urine pregnancy test, or intention of becoming pregnant.

          -  Acute or chronic liver disease for viral, autoimmune or metabolic cause,
             gastrointestinal dysfunction (different from those typical gastrointestinal symptoms
             of an acute attack of AIP), kidney disorder (renal impairment defined as plasma
             creatinine > 2 mg/dl (150 µmol/l)), severe respiratory disease, severe autoimmune
             disease or severe acute active infectious condition.

          -  Presence of adeno-associated virus type 5 (AAV5) neutralizing antibodies.

          -  Positive hepatitis B or C virus (HBV or HCV) serological test.

          -  Positive human immunodeficiency virus (HIV) serological test.

          -  History of drug (cannabis, cocaine, amphetamines, barbiturates) or alcohol abuse or
             addiction, during the three months preceding the initial visit.

          -  Current or previous participation in a gene therapy trial.

          -  Any other disease or condition that, in the opinion of the principal investigator,
             contraindicates their participation in the study because it can expose the patient to
             a risk or because disqualifies the patient to complete the timetable of the study.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Juan Ruiz, MD, , 

Location Countries

Spain

Location Countries

Spain

Administrative Informations


NCT ID

NCT02076763

Organization ID

DIG-API-2011-01

Secondary IDs

261506 AIPGene

Responsible Party

Sponsor

Study Sponsor

Digna Biotech S.L.

Collaborators

 Porphyria Centre Sweden

Study Sponsor

Juan Ruiz, MD, Study Chair, Digna Biotech S.L.


Verification Date

February 2014