NCT01916382

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
140

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Apr 2014

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 2, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 5, 2013

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 2, 2020

Completed
Last Updated

May 31, 2018

Status Verified

May 1, 2018

Enrollment Period

1.8 years

First QC Date

August 2, 2013

Last Update Submit

May 30, 2018

Conditions

Alkaptonuria

Keywords

Alkaptonuria, nitisinone,Ochronosis, Homogentisic acid

Outcome Measures

Primary Outcomes (1)

  • 24 houre Urine Homogentisic acid

    year 1

Study Arms (2)

Nitisinone

EXPERIMENTAL

Homogentisic acid lowering drug intervention

Drug: Nitisinone

No treatment

NO INTERVENTION

comparrator

Interventions

NitisinoneDRUG

drug

Also known as: Orfadin
Nitisinone

Eligibility Criteria

Age25 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A patient must fulfil the following criteria in order to be included in the study:
  • \. Diagnosis of AKU Any Clinical manifestations of AKU, such as clinical ochronosis or chronic back/joint pain.
  • \. Age ≥25 years. 4. Willing and able to visit the investigational site for study visits. 5. Signed written informed consent given.

You may not qualify if:

  • Currently pregnant or lactating.
  • Female patient of child-bearing potential not using a reliable method of contraception.
  • Known allergy to nitisinone or any of the constituents of the investigational product.
  • Current malignancy.
  • Uncontrolled hypertension (blood pressure greater than 180 mmHg systolic or greater than 95 mmHg diastolic).
  • Unstable cardiovascular disease.
  • Serum potassium \< 3.0 mmol/L.
  • eGFR \< 60 mL/min .
  • ALT \> 1.5 x upper limit of normal.
  • Haemoglobin \< 10.0 g/dL.
  • Platelets \< 100 x 109/L.
  • Total white blood count \< 3.0 x 109/L or neutrophil count \< 1.5 x 109/L.
  • History of alcohol or drug abuse.
  • Participation in another clinical study within 3 months of randomization.
  • Treatment with nitisinone within 60 days of randomization.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Royal Liverpool Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 36270742DERIVED

  • 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.

    PMID: 32822600DERIVED

MeSH Terms

Conditions

AlkaptonuriaOchronosis

Interventions

nitisinone

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • L Ranganath

    Liverpool University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

August 2, 2013

First Posted

August 5, 2013

Study Start

April 1, 2014

Primary Completion

February 1, 2016

Study Completion

February 2, 2020

Last Updated

May 31, 2018

Record last verified: 2018-05

Locations

GB(1)