Alpha-MannosidosisPhase 3NCT01681953
A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis
A Phase 3 study testing Lamazym in people with Alpha-Mannosidosis, run by Zymenex A/S at 6 sites in 5 countries.
Trial summary
The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis Read more about this study
- Who is it for?
- Ages 5 to 35 years
- Conditions the study is for
- Alpha-Mannosidosis
- What is being tested?
- Lamazym
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Aug 2012to May 2014
- Phase
- Phase 3
- 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 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities
- The subject and his/her guardian(s) must have the ability to comply with the protocol
- The subject must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-Mannosidase activity < 10% of normal activity (historical data)
- The subject must have an age at the time of screening ≥ 5 years and ≤ 35 years
- The subject must have the ability to physically and mentally cooperate in the tests
- The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial
Who cannot join
- The subjects diagnosis cannot be confirmed by alpha-Mannosidase activity < 10% of normal activity
- The subject cannot walk without support
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
- History of BMT
- 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
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
Show all 13Show fewer
- Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception
- Psychosis; any psychotic disease, also in remission, is an exclusion criteria
- Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
- Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months
- Adult patients who, in the opinion of the Investigator, would be unable to give consent, and who does not have any legal protection or guardianship
- Total IgE >800 IU/ml
- Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol)
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
France2 sites
Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel
Bron, 69677
Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter
Paris, 75 571
Denmark1 site
Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
Copenhagen, DK-2100
Germany1 site
Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1
Mainz, 55131
Poland1 site
The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20
Warsaw, 04 730
United Kingdom1 site
Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,
Manchester, M13 9WL
About this study
Official title: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis.
The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis
- Conditions
- Alpha-Mannosidosis
- Being tested
- Lamazym, Placebo
- 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, recombinant human alpha-mannosidase
ERT, i.v. infusions weekly
PlaceboDrug
Infusions weekly
| Study group | Role | What they receive |
|---|---|---|
| Lamazym | Active comparator | 1 mg Lamazym/kg body weight Receives: Drug: Lamazym |
| Placebo | Placebo comparator | Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of oligosaccharides in serum
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Measured: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
The number of steps climbed in 3 minutes (3-minute stair climb test)
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Measured: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Secondary outcomes (6)
Forced Vital Capacity
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Measured: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
The distance walked in 6 minutes (6-minute walk test)
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Measured: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Adverse Events
Safety endpoint assessed weekly throughout the trial
Measured: 1 week
Development of clinically significant changes in vital signs and change in physical examination
Safety endpoints assessed weekly throughout the trial
Measured: 1 week
Clinical laboratory parameters (hematology, biochemistry and urinalysis)
Safety endpoints assessed weekly throughout the trial
Measured: 1 week
Development of Lamazym antibodies and neutralizing/inhibitory antibodies
Safety endpoints assessed weekly throughout the trial
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 posted10 Sep 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 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, Copenhagen University Hospital, Center for Metabolic Diseases, Department for Clinical GeneticsJens Fogh, Study chair, Zymenex A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01681953
- Sponsor's protocol ID
- rhLAMAN-05
- Other IDs
- 2012-000979-17
- Status last verified
- Jul 2020
- First submitted
- 22 Aug 2012
- Last updated
- 3 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Borgwardt 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 26048034Borgwardt 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 26016802Harmatz P, Cattaneo F, Ardigo D, Geraci S, Hennermann JB, Guffon N, Lund A, Hendriksz CJ, Borgwardt L. Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis. Mol Genet Metab. 2018 Jun;124(2):152-160. doi: 10.1016/j.ymgme.2018.04.003. Epub 2018 Apr 18.
PubMed 29716835Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigo D, Cattaneo F, Fogh J, Van den Hout JMH, Beck M, Jones SA, Tylki-Szymanska A, Haugsted U, Lund AM. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0. Epub 2018 May 30.
PubMed 29846843
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 Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis.
- ClinicalTrials.gov ID
- NCT01681953
- Acronym / sponsor ID
- rhLAMAN-05
- Conditions
- Alpha-Mannosidosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Zymenex A/SIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- Aug 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 10 Sep 2012 (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.
The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lamazym | Active comparator | Drug: Lamazym1 mg Lamazym/kg body weight |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo is formulated as an isotonic phosphate buffer with glycine and mannitol |
Who may qualify
- Ages
- 5 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities
- The subject and his/her guardian(s) must have the ability to comply with the protocol
- The subject must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-Mannosidase activity < 10% of normal activity (historical data)
- The subject must have an age at the time of screening ≥ 5 years and ≤ 35 years
- The subject must have the ability to physically and mentally cooperate in the tests
Key exclusion criteria (13 listed)
- The subjects diagnosis cannot be confirmed by alpha-Mannosidase activity < 10% of normal activity
- The subject cannot walk without support
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
- History of BMT
- 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
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: rhLAMAN, recombinant human alpha-mannosidaseERT, i.v. infusions weekly | Drug | Lamazym |
| PlaceboInfusions weekly | Drug | Placebo |
Primary outcome
Reduction of oligosaccharides in serum
Time frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
The number of steps climbed in 3 minutes (3-minute stair climb test)
Time frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
6 secondary outcomes
Forced Vital Capacity
Time frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
The distance walked in 6 minutes (6-minute walk test)
Time frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Adverse Events
Time frame: 1 week
Development of clinically significant changes in vital signs and change in physical examination
Time frame: 1 week
Clinical laboratory parameters (hematology, biochemistry and urinalysis)
Time frame: 1 week
Development of Lamazym antibodies and neutralizing/inhibitory antibodies
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 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.
- 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.
- Background: PubMed 29716835Harmatz P, Cattaneo F, Ardigo D, Geraci S, Hennermann JB, Guffon N, Lund A, Hendriksz CJ, Borgwardt L. Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis. Mol Genet Metab. 2018 Jun;124(2):152-160. doi: 10.1016/j.ymgme.2018.04.003. Epub 2018 Apr 18.
- Results publication: PubMed 29846843Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigo D, Cattaneo F, Fogh J, Van den Hout JMH, Beck M, Jones SA, Tylki-Szymanska A, Haugsted U, Lund AM. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0. Epub 2018 May 30.
- 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
Copenhagen University Hospital, Center for Metabolic Diseases, Department for Clinical Genetics
Jens Fogh study chair
Zymenex A/S
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lamazym in people with Alpha-Mannosidosis, run by Zymenex A/S at 6 sites in 5 countries.
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 6 inclusion and 13 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.
Where is the study taking place?
The record lists 6 sites in France, Denmark, Germany, Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Reduction of oligosaccharides in serum (time frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks). The study lists 2 primary outcomes in all. 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 NCT01681953, which also lists 4 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.