ALXN1101 in Pediatric Patients with MoCD Type A treated with rcPMP
Research type
Research Study
Full title
A Phase 2, Multicenter, Multinational, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of ORGN001 (formerly ALXN1101) in Pediatric Patients with Molybdenum Cofactor Deficiency (MoCD) Type A Currently Treated with Recombinant Escherichia coli-derived Cyclic Pyranopterin Monophosphate (rcPMP)
IRAS ID
141441
Contact name
Sarah Hughes
Contact email
Sponsor organisation
Origin Biosciences, Inc.
Eudract number
2013-002701-56
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 6 months, 30 days
Research summary
Research Summary
Molybdenum Cofactor Deficiency Disorder (MoCD) is a rare condition in which the body is not able to produce “cyclic pyranopterin monophosphate” (cPMP). This causes a build‐up of a toxin called sulphite which in turn results in damage to the central nervous system (brain). MoCD is usually diagnosed in babies once they are born and causes symptoms such as seizures, involuntary movements and difficulties in feeding. Currently, there are no approved treatments for MoCD.
Colbourne Pharmaceuticals (“Colbourne”) have made a form of cPMP (Recombinant Escherichia coli‐derived Cyclic Pyranopterin Monophosphate (rcPMP) available on a named patient basis. Alexion Pharma International Sàrl (Alexion) have developed a new synthetic form of cPMP called ALXN1101 based on certain rights it acquired in 2011 from Orphatec Pharmaceuticals (now Colbourne). ALXN1101 contains the same active ingredient as rcPMP and is expected to work in the same way to treat MoCD.
This study is designed to switch children being treated with rcPMP, to the synthetic form ALXN1101, and to see if ALXN1101 is safe and effective in treating paediatric MoCD.
To date, ALXN1101 has been tested in healthy adults in an ongoing research study. However, this will be the first study where ALXN1101 will be given to children. At least 4 children with MoCD will participate in this study at study centres worldwide.
Summary of Results
Abstract Purpose of the study: To see if children with molybdenum cofactor deficiency type A could safely transition from a former treatment (rcPMP) to fosdenopterin without any negative effect.
What was tested: Fosdenopterin was tested in a phase 2 study. In a phase 2 study, a new treatment is tested on a small number of patients.
People who took part in this study: 8 children, from 8 months to approximately 6 years old, across 5 countries.
Results: Children with molybdenum cofactor deficiency type A were able to switch safely from an rcPMP to fosdenopterin without any negative effect.
Safety: 3 children experienced a side effect considered to be related to fosdenopterin (1 rash, 1 redness of the skin, 1 issue with the infusion kit). Who sponsored this study?
The sponsor of this study was Origin Biosciences, Inc. (Origin).
Sponsor address:
1800 Owens Street
Suite C-1200
San Francisco, CA USA 94158Origin would like to thank the families who participated in this clinical study.
General information about the study
Where was the study done?
This study took place in the following countries: Australia, Tunisia, the Netherlands, the United Kingdom, and the United States.
When was this study done?
This study started on 02 April 2014 and ended on 03 August 2022.
Which disease was studied?
This study was about molybdenum cofactor deficiency type A, a rare inherited disease. Patients with this disease do not have enough of a substance called ‘cyclic pyranopterin monophosphate (cPMP)’ which the body needs to make a compound called ‘molybdenum cofactor’. In the absence of molybdenum cofactor, toxic substances accumulate in the brain causing damage. Children suffering from this condition can have uncontrolled body movements, difficulties moving parts of the body, difficulties feeding, growth issues, and eventually die in the absence of treatment.
The study treatment, fosdenopterin, corrects the lack of cPMP, thus restores cPMP-related processes in the brain.
What was the main objective of this study?
Before fosdenopterin existed, the only option for children with molybdenum cofactor deficiency type A was a form of cPMP called ‘recombinant cPMP (rcPMP)’that was administered on a case-by-case basis. However, it did not meet all quality standards that are usually expected for drugs, whereas fosdenopterin does. As fosdenopterin contains the same active ingredient, it was expected to work in the same way. The objective of this study was to see if children receiving rcPMP could safely transition to fosdenopterin without impact on efficacy.
In this study, all the patients received fosdenopterin at increasing doses. This was to see the maximum dose they could take without having severe side effects.
There was no minimum or maximum number of patients specified for this study.
Who participated in this study?
Boys and girls being treated with rcPMP for molybdenum cofactor deficiency type A were included after the parents/guardians’ approval was obtained.
This study included 8 children: 3 in the United Kingdom, 2 in the Netherlands, 1 in Tunisia, 1 in Australia, and 1 in the United States. They were 5 girls and 3 boys. The youngest received the first dose of fosdenopterin at 8 months and the oldest at approximately 6 years of age.
Which medicine was studied?
Fosdenopterin was the medicine studied. It is also known as ‘ORGN001’ and ‘ALXN1101’.
Just before they started to receive fosdenopterin, the patients stopped receiving rcPMP. Fosdenopterin was administered each day through a vein. The starting amount of medicine was the same one as they received while on rcPMP and depended on the child’s weight. After the first 2 months of treatment, the amount of medicine was increased every month up to the 5th month, unless there were severe side effects. The amount of medicine was increased in all children without severe side effects.
What side effects did the patients have?
Researchers recorded as ‘side effects’, medical problems that happened during the study that they believed to be related to the treatment in the study.
Serious side effects are life-threatening reactions, requiring the individual to go to the hospital or causing lasting problems. During this study, no patient experienced serious side effects.
Three out of the 8 children experienced a side effect that the study doctors believed to be related to fosdenopterin:
• Fosdenopterin is administered through a vein via an infusion kit: the bag containing the drug is connected to a tube, the tube to a needle, and the needle to the vein. One child had an issue with this infusion kit.
• 1 child experienced a rash on the face.
• 1 child experienced redness of the skin upon sun exposure.
What were the overall results of the study?
For all patients, the signs of the disease and quantities of toxic substances in their blood and urine were stable after switching from rcPMP to fosdenopterin. The amount of some toxic substances even decreased. Also, all children gained weight, grew taller and had some head growth. Their motor function, the capacity to gain knowledge and abilities were stable or improved after switching from rcPMP to fosdenopterin. The way children fed did not change over time and most children who fed by mouth at the beginning of the study still did at the end of their participation.
In conclusion, children with molybdenum cofactor deficiency type A were able to switch safely from rcPMP to fosdenopterin without any negative impact.
How has this study helped patients and researchers?
The study showed that fosdenopterin has comparable effects to rcPMP. This supports its use as a replacement therapy for patients with molybdenum cofactor deficiency type A. However, due to the rarity of the disease, there was a very small number (8) of patients.
Please remember that researchers look at the results of many studies to understand which drugs work and how they work. It takes lots of people in many studies all around the world to advance medical science. This summary only shows the results from this one study. Other studies may find different results.
Are further studies planned?
No further clinical studies with fosdenopterin are planned by Origin Biosciences, Inc. at the current time.
Where can I learn more about this study?
To learn more about this study, you can find more detailed information on these websites:
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ceba23ac9373e4a7a1f5308dbd3cd6866%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638336651401020273%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=CANdjdOL7p7ikMd0B5aVFTSHAZpNnqXvTejGKXoQSM0%3D&reserved=0
Use the identifier NCT02047461
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ceba23ac9373e4a7a1f5308dbd3cd6866%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638336651401020273%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=w9PsofJiQMy2jj4g3pe0pHJiL2WJUNGoZLYHHdGL6T4%3D&reserved=0
Use the identifier 2013-002701-56REC name
West of Scotland REC 1
REC reference
14/WS/0052
Date of REC Opinion
16 Apr 2014
REC opinion
Further Information Favourable Opinion