Alpha MannosidosisPhase 1NCT01268358
Safety Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
A Phase 1 study testing Lamazym in people with Alpha Mannosidosis, run by Zymenex A/S.
Trial summary
This is a single-center, open-label, dose escalation study of patients with alpha-mannosidosis. 10 patients will be enrolled in this study receiving intravenous infusions of Lamazym. Read more about this study
- Who is it for?
- Ages 5 to 20 years
- Conditions the study is for
- Alpha Mannosidosis
- What is being tested?
- Lamazym
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Oct 2010to Jan 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- The patient must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity in blood leukocytes
- The patient must have an age at the time of screening ≥ 5 year and ≤ 20 years
- The patient must have physical ability to perform 6-minutes walk test (6MWT), 3 minute-stair climb test (3MSCT) and pulmonary lung function test (spirometry, body plethysmography).
- The patient must have the ability to mentally cooperate in the cognitive and motor function tests
- The patient must have the ability to hear and follow a request. Hearing aids can be worn.
- Patient or patient's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
- The patient and his/her guardian(s) must have the ability to comply with the protocol
Who cannot join
- The patient cannot walk without support.
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
- History of bone marrow transplantation
- Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
- Presence of an ECHO with abnormalities within half a year that, in the opinion of the Investigator, would preclude participation in the trial
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial
- Pregnancy
- Psychosis within the last 3 months
About this study
Official title: A Single Center, Open-label, Dose Escalation Study of the Safety and Pharmacokinetics of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) for the Treatment of Patients With Alpha-mannosidosis.
This is a single-center, open-label, dose escalation study of patients with alpha-mannosidosis. 10 patients will be enrolled in this study receiving intravenous infusions of Lamazym. In order to avoid development of delayed hypersensitivity all patients will continue weekly treatment at the designated dose until the Safety Committee approves transfer to the rhLAMAN-03 protocol.
It is the hypothesis that Lamazym is safe to use.
- Conditions
- Alpha Mannosidosis
- Being tested
- Lamazym
- Medical subject headings
- alpha-Mannosidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamazymDrug
Also called rhLAMAN
Lamazym, ERT, infusion weekly
| Study group | Role | What they receive |
|---|---|---|
| Lamazym 6.25 | Experimental | Not described Receives: Drug: Lamazym |
| Lamazym 12.5 | Experimental | Not described Receives: Drug: Lamazym |
| Lamazym 25 | Experimental | Not described Receives: Drug: Lamazym |
| Lamazym 50 | Experimental | Not described Receives: Drug: Lamazym |
| Lamazym 100 | Experimental | Not described Receives: Drug: Lamazym |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety profile of rhLAMAN (Lamazym)
Measured: 1-5 weeks
Secondary outcomes (2)
To determine the PK profile of rhLAMAN (Lamazym) in patients with alpha-mannosidosis as measured by rhLAMAN levels in plasma
Measured: 1 dosis
To collect baseline measurements that are to be used for efficacy evaluation in the following trial (rhLAMAN-03)
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2010 (estimated)
- Study startOct 2010
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alpha MannosidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zymenex A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Allan M. Lund, MD, Principal investigator, Department of Clinical Genetics, Juliane Marie Centre, Region Hovedstaden, Copenhagen University hospital, DenmarkJens Fogh, Study chair, Zymenex A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01268358
- Sponsor's protocol ID
- rhLAMAN-02
- Other IDs
- 2010-022084-36
- Status last verified
- Jul 2020
- First submitted
- 29 Dec 2010
- Last updated
- 3 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Borgwardt L, Thuesen AM, Olsen KJ, Fogh J, Dali CI, Lund AM. Cognitive profile and activities of daily living: 35 patients with alpha-mannosidosis. J Inherit Metab Dis. 2015 Nov;38(6):1119-27. doi: 10.1007/s10545-015-9862-4. Epub 2015 May 28.
PubMed 26016802Borgwardt L, Dali CI, Fogh J, Mansson JE, Olsen KJ, Beck HC, Nielsen KG, Nielsen LH, Olsen SO, Riise Stensland HM, Nilssen O, Wibrand F, Thuesen AM, Pearl T, Haugsted U, Saftig P, Blanz J, Jones SA, Tylki-Szymanska A, Guffon-Fouiloux N, Beck M, Lund AM. Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study. J Inherit Metab Dis. 2013 Nov;36(6):1015-24. doi: 10.1007/s10545-013-9595-1. Epub 2013 Mar 14.
PubMed 23494656Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
PubMed 26048034
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Open-label, Dose Escalation Study of the Safety and Pharmacokinetics of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) for the Treatment of Patients With Alpha-mannosidosis.
- ClinicalTrials.gov ID
- NCT01268358
- Acronym / sponsor ID
- rhLAMAN-02
- Conditions
- Alpha Mannosidosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Zymenex A/SIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- Oct 2010
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 30 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, open-label, dose escalation study of patients with alpha-mannosidosis. 10 patients will be enrolled in this study receiving intravenous infusions of Lamazym. In order to avoid development of delayed hypersensitivity all patients will continue weekly treatment at the designated dose until the Safety Committee approves transfer to the rhLAMAN-03 protocol.
It is the hypothesis that Lamazym is safe to use.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Lamazym 6.25 | Experimental | Drug: Lamazym |
| Lamazym 12.5 | Experimental | Drug: Lamazym |
| Lamazym 25 | Experimental | Drug: Lamazym |
| Lamazym 50 | Experimental | Drug: Lamazym |
| Lamazym 100 | Experimental | Drug: Lamazym |
Who may qualify
- Ages
- 5 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- The patient must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity in blood leukocytes
- The patient must have an age at the time of screening ≥ 5 year and ≤ 20 years
- The patient must have physical ability to perform 6-minutes walk test (6MWT), 3 minute-stair climb test (3MSCT) and pulmonary lung function test (spirometry, body plethysmography).
- The patient must have the ability to mentally cooperate in the cognitive and motor function tests
- The patient must have the ability to hear and follow a request. Hearing aids can be worn.
Key exclusion criteria (8 listed)
- The patient cannot walk without support.
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
- History of bone marrow transplantation
- Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
- Presence of an ECHO with abnormalities within half a year that, in the opinion of the Investigator, would preclude participation in the trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LamazymAlso: rhLAMANLamazym, ERT, infusion weekly | Drug | Lamazym 100, Lamazym 12.5, Lamazym 25, Lamazym 50, Lamazym 6.25 |
Primary outcome
To evaluate the safety profile of rhLAMAN (Lamazym)
Time frame: 1-5 weeks
2 secondary outcomes
To determine the PK profile of rhLAMAN (Lamazym) in patients with alpha-mannosidosis as measured by rhLAMAN levels in plasma
Time frame: 1 dosis
To collect baseline measurements that are to be used for efficacy evaluation in the following trial (rhLAMAN-03)
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Background: PubMed 26016802Borgwardt L, Thuesen AM, Olsen KJ, Fogh J, Dali CI, Lund AM. Cognitive profile and activities of daily living: 35 patients with alpha-mannosidosis. J Inherit Metab Dis. 2015 Nov;38(6):1119-27. doi: 10.1007/s10545-015-9862-4. Epub 2015 May 28.
- Results publication: PubMed 23494656Borgwardt L, Dali CI, Fogh J, Mansson JE, Olsen KJ, Beck HC, Nielsen KG, Nielsen LH, Olsen SO, Riise Stensland HM, Nilssen O, Wibrand F, Thuesen AM, Pearl T, Haugsted U, Saftig P, Blanz J, Jones SA, Tylki-Szymanska A, Guffon-Fouiloux N, Beck M, Lund AM. Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study. J Inherit Metab Dis. 2013 Nov;36(6):1015-24. doi: 10.1007/s10545-013-9595-1. Epub 2013 Mar 14.
- Results publication: PubMed 26048034Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan M. Lund, MD principal investigator
Department of Clinical Genetics, Juliane Marie Centre, Region Hovedstaden, Copenhagen University hospital, Denmark
Jens Fogh study chair
Zymenex A/S
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lamazym in people with Alpha Mannosidosis, run by Zymenex A/S.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety profile of rhLAMAN (Lamazym) (time frame: 1-5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01268358, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.