Alpha-MannosidosisPhase 2rhLaman-08NCT02998879
Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis
A Phase 2 study testing Velmanase Alfa (e.g. Lamazym) in people with Alpha-Mannosidosis, run by Chiesi Farmaceutici S.p.A. at 6 sites in 5 countries.
Trial summary
The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years Read more about this study
- Who is it for?
- Ages Up to 6 years
- Conditions the study is for
- Alpha-Mannosidosis
- What is being tested?
- Velmanase Alfa (e.g. Lamazym)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Dec 2016to Jul 2020
- Phase
- Phase 2
- 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 Up to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient's custodial parent(s) must provide signed ICF prior to the involvement of the patient in any trial-related activities
- The subject's custodial parent(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 in leukocytes or fibroblasts < 10% of normal activity (historical data)
- The subject must have an age at the time of screening < 6 years.
Who cannot join
- The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
- 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
- Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
- Participation in other interventional trials testing the IMP within the last 3 months.
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
About this study
Official title: A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years of Age With Alpha-Mannosidosis
The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years
Read the detailed description
The Primary endpoints of the study include:
- Safety and tolerability of velmanase alfa as per Adverse events (AEs, including IRR), vital signs, laboratory parameters (hematology, biochemistry and urinanalysis)
- Detection of anti-velmanase alfa antibodies and neutralizing/inhibitory antibodies
The Secondary endpoints include changes from baseline to 24 months for the following parameters. Efficacy outcomes:
- Serum oligosaccharides
- Functional capacity: Peabody Developmental Motor Scale - 2nd edition (PDMS-2) scores, Mullen's Scale of Early Learning (MSEL) scores, Bruininks-Oseretsky Test Of Motor Proficiency-2nd Edition (BOT-2), when applicable by age (from 4 years) or upon the judgment of the physician
- Endurance: 3-Minute Stair Climb Test (3MSCT) and 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician, 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age, or when applicable according to the judgment of the physician
- Hearing evaluation: Otoacoustic Emissions (OAE) testing, Automatic Auditory Brainstem Response (A-ABR) audiometry
- Immunological profile, when applicable upon the judgment of the physician:
- CSF biomarkers: Tau protein (Tau), Neurofilament Protein Light (NFL), Glial Fibrillary Acidic Protein (GFAp), Oligosaccharides
- Assessment of quality of life via Questionnaire to parents
- Assessment of mannose-rich oligosaccharides in brain tissue, MRI
- Pharmacokinetic parameters
- Conditions
- Alpha-Mannosidosis
- Being tested
- Velmanase Alfa (e.g. 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.
Velmanase Alfa (e.g. Lamazym)Drug
Also called Lamazym
iv infusion treatment
| Study group | Role | What they receive |
|---|---|---|
| Velmanase Alfa | Experimental | velmanase alfa 1mg/kg body weight infusion Receives: Drug: Velmanase Alfa (e.g. Lamazym) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of velmanase alfa as per Adverse events
Safety and tolerability assessed as per AEs including infusion-related reactions [IRRs]
Measured: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per vital signs
Measured: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per hematology
Measured: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per blood biochemistry
Measured: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per urinalysis
Measured: From baseline throughout study completion, at least of 2 years
Detection of anti-velmanase alfa-IgG antibodies (ADA) and neutralizing/inhibitory antibodies
Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained
Measured: From baseline throughout study completion, at least of 2 years
Secondary outcomes (22)
Evaluation of levels of Serum oligosaccharides
Assessment of change from baseline in levels of Serum oligosaccharides
Measured: From baseline throughout study completion, at least for 2 years
Functional capacity: The Peabody Developmental Motor Scale test (PDMS-2)
Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained
Measured: From baseline throughout study completion, at least for 2 years
Functional capacity: Bruininks-Oseretsky test of Motor Proficiency (BOT-2) when applicable by age (from 4 years) or upon the judgment of the physician
Measured: From baseline throughout study completion, at least for 2 years
Functional capacity: Mullen Scales of Early Learning (MSEL)
Measured: From baseline throughout study completion, at least for 2 years
Endurance: 3-Minute Stair Climb Test (3MSCT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician
Measured: From baseline throughout study completion, at least for 2 years
Endurance: 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age
Measured: From baseline throughout study completion, at least for 2 years
Hearing evaluation: Otoacoustic Emissions (OAE) testing
Measured: From baseline throughout study completion, at least for 2 years
Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry
Measured: From baseline throughout study completion, at least for 2 years
Immunological profile when applicable upon the judgement of the physician (Serum IgG, IgA, IgM; in vitro synthesis of IgG; in vitro proliferative response and Immunophenotype)
Measured: From baseline throughout study completion, at least for 2 years
CSF biomarkers: Tau protein (Tau) § Neurofilament Protein Light (NFL) § Glial Fibrillary Acidic Protein (GFAp) § Oligosaccharides
Measured: From baseline throughout study completion, at least for 2 years
Assessment of quality of life via Questionnaire
Measured: From baseline throughout study completion, at least for 2 years
Assessment of mannose-rich oligosaccharides in brain tissue, as measured by Magnetic Resonance Spectroscopy (MRS)
Measured: From baseline throughout study completion, at least for 2 years
Magnetic Resonance Imaging (MRI) in white matter, gray matter and in centrum semi ovale, and diffusion-MRI of the brain,
Measured: From baseline throughout study completion, at least for 2 years
Pharmacokinetic parameters to determine Cmax (Peak Concentration)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Area Under Curve (AUC24)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine AUClast (Area Under Curve After The Last Count)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine AUCinf (Area Under Curve From Time Zero To Infinity)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine tmax (Time To Peak Concentration)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine CL (Clearance)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life)
Measured: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio
Measured: At first dose (visit 1) and after 6 months (visit 26)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2016 (estimated)
- Study startDec 2016
- Primary completionJul 2020
- Study completionJul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha-MannosidosisStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02998879
- Sponsor's protocol ID
- CCD-LMZYMAA1-08
- Other IDs
- 2016-001988-36, 2016
- Acronym
- rhLaman-08
- Status last verified
- Oct 2021
- First submitted
- 25 Nov 2016
- Last updated
- 26 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years of Age With Alpha-Mannosidosis
- ClinicalTrials.gov ID
- NCT02998879
- Acronym / sponsor ID
- rhLaman-08 / CCD-LMZYMAA1-08
- Conditions
- Alpha-Mannosidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Study start
- Dec 2016
- Primary completion
- Jul 2020 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 21 Dec 2016 (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 main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years
Detailed description
The Primary endpoints of the study include:
- Safety and tolerability of velmanase alfa as per Adverse events (AEs, including IRR), vital signs, laboratory parameters (hematology, biochemistry and urinanalysis)
- Detection of anti-velmanase alfa antibodies and neutralizing/inhibitory antibodies
The Secondary endpoints include changes from baseline to 24 months for the following parameters. Efficacy outcomes:
- Serum oligosaccharides
- Functional capacity: Peabody Developmental Motor Scale - 2nd edition (PDMS-2) scores, Mullen's Scale of Early Learning (MSEL) scores, Bruininks-Oseretsky Test Of Motor Proficiency-2nd Edition (BOT-2), when applicable by age (from 4 years) or upon the judgment of the physician
- Endurance: 3-Minute Stair Climb Test (3MSCT) and 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician, 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age, or when applicable according to the judgment of the physician
- Hearing evaluation: Otoacoustic Emissions (OAE) testing, Automatic Auditory Brainstem Response (A-ABR) audiometry
- Immunological profile, when applicable upon the judgment of the physician:
- CSF biomarkers: Tau protein (Tau), Neurofilament Protein Light (NFL), Glial Fibrillary Acidic Protein (GFAp), Oligosaccharides
- Assessment of quality of life via Questionnaire to parents
- Assessment of mannose-rich oligosaccharides in brain tissue, MRI
- Pharmacokinetic parameters
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velmanase Alfa | Experimental | Drug: Velmanase Alfa (e.g. Lamazym)velmanase alfa 1mg/kg body weight infusion |
Who may qualify
- Ages
- Up to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Patient's custodial parent(s) must provide signed ICF prior to the involvement of the patient in any trial-related activities
- The subject's custodial parent(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 in leukocytes or fibroblasts < 10% of normal activity (historical data)
- The subject must have an age at the time of screening < 6 years.
Key exclusion criteria (7 listed)
- The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
- 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
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 |
|---|---|---|
| Velmanase Alfa (e.g. Lamazym)Also: Lamazymiv infusion treatment | Drug | Velmanase Alfa |
Primary outcome
Safety and tolerability of velmanase alfa as per Adverse events
Time frame: From baseline throughout study completion, at least of 2 years
Safety and tolerability assessed as per AEs including infusion-related reactions [IRRs]
Safety and tolerability of velmanase alfa as per vital signs
Time frame: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per hematology
Time frame: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per blood biochemistry
Time frame: From baseline throughout study completion, at least of 2 years
Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per urinalysis
Time frame: From baseline throughout study completion, at least of 2 years
Detection of anti-velmanase alfa-IgG antibodies (ADA) and neutralizing/inhibitory antibodies
Time frame: From baseline throughout study completion, at least of 2 years
Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained
22 secondary outcomes
Evaluation of levels of Serum oligosaccharides
Time frame: From baseline throughout study completion, at least for 2 years
Functional capacity: The Peabody Developmental Motor Scale test (PDMS-2)
Time frame: From baseline throughout study completion, at least for 2 years
Functional capacity: Bruininks-Oseretsky test of Motor Proficiency (BOT-2) when applicable by age (from 4 years) or upon the judgment of the physician
Time frame: From baseline throughout study completion, at least for 2 years
Functional capacity: Mullen Scales of Early Learning (MSEL)
Time frame: From baseline throughout study completion, at least for 2 years
Endurance: 3-Minute Stair Climb Test (3MSCT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician
Time frame: From baseline throughout study completion, at least for 2 years
Endurance: 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age
Time frame: From baseline throughout study completion, at least for 2 years
Hearing evaluation: Otoacoustic Emissions (OAE) testing
Time frame: From baseline throughout study completion, at least for 2 years
Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry
Time frame: From baseline throughout study completion, at least for 2 years
Immunological profile when applicable upon the judgement of the physician (Serum IgG, IgA, IgM; in vitro synthesis of IgG; in vitro proliferative response and Immunophenotype)
Time frame: From baseline throughout study completion, at least for 2 years
CSF biomarkers: Tau protein (Tau) § Neurofilament Protein Light (NFL) § Glial Fibrillary Acidic Protein (GFAp) § Oligosaccharides
Time frame: From baseline throughout study completion, at least for 2 years
Assessment of quality of life via Questionnaire
Time frame: From baseline throughout study completion, at least for 2 years
Assessment of mannose-rich oligosaccharides in brain tissue, as measured by Magnetic Resonance Spectroscopy (MRS)
Time frame: From baseline throughout study completion, at least for 2 years
Magnetic Resonance Imaging (MRI) in white matter, gray matter and in centrum semi ovale, and diffusion-MRI of the brain,
Time frame: From baseline throughout study completion, at least for 2 years
Pharmacokinetic parameters to determine Cmax (Peak Concentration)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Area Under Curve (AUC24)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine AUClast (Area Under Curve After The Last Count)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine AUCinf (Area Under Curve From Time Zero To Infinity)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine tmax (Time To Peak Concentration)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine CL (Clearance)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life)
Time frame: At first dose (visit 1) and after 6 months (visit 26)
Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio
Time frame: At first dose (visit 1) and after 6 months (visit 26)
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 26 Oct 2021.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Velmanase Alfa (e.g. Lamazym) in people with Alpha-Mannosidosis, run by Chiesi Farmaceutici S.p.A. 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 4 inclusion and 7 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 26 Oct 2021. 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 Germany, Austria, Denmark, France, Italy. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety and tolerability of velmanase alfa as per Adverse events (time frame: From baseline throughout study completion, at least of 2 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Oct 2021.