Observational Study of Acute Intermittent Porphyria Patients

NCT02076763 | Completed

• 2 other identifiers: DIG-API-2011-01261506 AIPGene
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Intermittent Porphyria

Keywords

Observational; Porphyria

Outcome Measures

Primary Outcomes (1)

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

  The primary objective of this study is to observe the changes of PBG and ALA urinary levels in acute intermittent porphyria patients. The patient will collect an early morning single urine sample protected from light, for the determination of PBG and ALA during each of the study visits (inclusion, follow-up and final visits). If hemin or glucose treatments were necessary, the patient should collect a urine sample before treatment administration, and sent it or carry it to the local investigation center.

  up to 24 months

Secondary Outcomes (5)

• Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations

  up to 24 months

• Psychological evaluation of patients

  up to 24 months

• Health related quality of life

  up to 24 months

• Frequency of AIP symptoms

  up to 24 months

• Frequency of treatments for AIP symptoms

  up to 24 months

Other Outcomes (2)

• Immunogenicity analysis

  up to 24 months

• Biological markers identification

  up to 24 months

Study Arms (1)

Acute intermittent porphyria

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).

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Acute intermitent porphyria patients, with a severe condition. And genetic confirmation of Porphobilinogen deaminase mutation.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Digna Biotech S.L.: lead
• Porphyria Centre Sweden: collaborator
• University of Navarra: collaborator
• UniQure N.V.: collaborator

Study Sites (2)

12 Octubre Hospital

Madrid, Madrid, 28041, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Related Publications (2)

• Jerico D, Luis EO, Cusso L, Fernandez-Seara MA, Morales X, Cordoba KM, Benito M, Sampedro A, Larriva M, Ramirez MJ, de Salamanca RE, Ortiz-de-Solorzano C, Alegre M, Prieto J, Lanciego JL, D'Avola D, Gonzalez-Aseguinolaza G, Pastor MA, Desco M, Fontanellas A. Brain ventricular enlargement in human and murine acute intermittent porphyria. Hum Mol Genet. 2020 Nov 25;29(19):3211-3223. doi: 10.1093/hmg/ddaa204.

  PMID: 32916704 DERIVED

• D'Avola D, Lopez-Franco E, Sangro B, Paneda A, Grossios N, Gil-Farina I, Benito A, Twisk J, Paz M, Ruiz J, Schmidt M, Petry H, Harper P, de Salamanca RE, Fontanellas A, Prieto J, Gonzalez-Aseguinolaza G. Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria. J Hepatol. 2016 Oct;65(4):776-783. doi: 10.1016/j.jhep.2016.05.012. Epub 2016 May 17.

  PMID: 27212246 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum, urine

MeSH Terms

Conditions

Porphyria, Acute Intermittent; Porphyrias

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Juan Ruiz, MD

  Digna Biotech S.L.

  STUDY CHAIR

• Jesus Prieto, MD

  Clinica Universidad de Navarra

  PRINCIPAL INVESTIGATOR

• Rafael Enriquez de Salamanca, MD

  Hospital 12 Octubre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 4, 2014
• Study Start: August 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: February 1, 2014
• Last Updated: March 12, 2014

Record last verified: 2014-02

Locations

ES (2)