Clinical trial NCT01916382: Suitability of Nitisinone in Alkaptonuria 2
Official title: An International, Multicentre, Randomised, Evaluator-blind, No-treatment Controlled, Parallel-group Study to Assess the Efficacy and Safety of Once Daily Nitisinone in Patients With Alkaptonuria After 12 Months of Treatment, Followed by an Additional 36 Month Treatment Period.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Alkaptonuria
Keywords: Alkaptonuria, nitisinone,Ochronosis, Homogentisic acid
Lead sponsor: University of Liverpool
Sponsor class: OTHER
First posted: 2013-08-05
Enrollment: 140
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a proposal to develop the orphan designated drug, nitisinone, for the treatment of a rare Mendelian disease, Alkaptonuria (AKU). Thanks to our existing successful fundamental and clinical research (cell models, animal models, natural history studies), we are now ready for this final stage of clinical development of nitisinone for AKU: a phase 3 clinical trial to prove efficacy. The results of DevelopAKUre will allow us to make the case to the European Medicines Agency for marketing authorisation of nitisinone for AKU, thereby contributing to the goal of the International Rare Diseases Research Consortium of developing 200 new therapies by 2020.


Eligibility criteria: Inclusion Criteria:

A patient must fulfil the following criteria in order to be included in the study:

1. Diagnosis of AKU Any Clinical manifestations of AKU, such as clinical ochronosis or chronic back/joint pain.

3. Age ≥25 years. 4. Willing and able to visit the investigational site for study visits. 5. Signed written informed consent given.

-

Exclusion Criteria:

The presence of any of the following will exclude a patient from inclusion in the study:

1. Currently pregnant or lactating.
2. Female patient of child-bearing potential not using a reliable method of contraception.
3. Known allergy to nitisinone or any of the constituents of the investigational product.
4. Current malignancy.
5. Uncontrolled hypertension (blood pressure greater than 180 mmHg systolic or greater than 95 mmHg diastolic).
6. Unstable cardiovascular disease.
7. Serum potassium \< 3.0 mmol/L.
8. eGFR \< 60 mL/min .
9. ALT \> 1.5 x upper limit of normal.
10. Haemoglobin \< 10.0 g/dL.
11. Platelets \< 100 x 109/L.
12. Total white blood count \< 3.0 x 109/L or neutrophil count \< 1.5 x 109/L.
13. History of alcohol or drug abuse.
14. Participation in another clinical study within 3 months of randomization.
15. Treatment with nitisinone within 60 days of randomization.
16. Psychiatric or somatic illness that interferes with compliance or communication with health care personnel.
17. Foreseeable inability to cooperate with given instructions or study procedures.
18. Any other medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion.

    -

Primary outcomes:
measure: 24 houre Urine Homogentisic acid
timeFrame: year 1
Secondary outcomes:
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital
state: Merseyside
Study officials:
affiliation: Liverpool University Hospitals NHS Foundation Trust
name: L Ranganath
role: PRINCIPAL_INVESTIGATOR
References:
citation: Imrich R, Sedlakova J, Ulehlova M, Gornall M, Jackson R, Olsson B, Rudebeck M, Gallagher J, Lukacova O, Mlynarikova V, Stancik R, Vrtikova E, Zanova E, Zatkova A, Arnoux JB, Rovensky J, Luangrath E, Bygott H, Khedr M, Ranganath LR. Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone. RMD Open. 2022 Oct;8(2):e002422. doi: 10.1136/rmdopen-2022-002422.
citation: Ranganath LR, Psarelli EE, Arnoux JB, Braconi D, Briggs M, Broijersen A, Loftus N, Bygott H, Cox TF, Davison AS, Dillon JP, Fisher M, FitzGerald R, Genovese F, Glasova H, Hall AK, Hughes AT, Hughes JH, Imrich R, Jarvis JC, Khedr M, Laan D, Le Quan Sang KH, Luangrath E, Lukacova O, Milan AM, Mistry A, Mlynarikova V, Norman BP, Olsson B, Rhodes NP, Rovensky J, Rudebeck M, Santucci A, Shweihdi E, Scott C, Sedlakova J, Sireau N, Stancik R, Szamosi J, Taylor S, van Kan C, Vinjamuri S, Vrtikova E, Webb C, West E, Zanova E, Zatkova A, Gallagher JA. Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2020 Sep;8(9):762-772. doi: 10.1016/S2213-8587(20)30228-X. Epub 2020 Aug 18.