Alpha-MannosidosisPhase 3SHAMANNCT04031066
Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
A Phase 3 study testing Velmanase Alfa in people with Alpha-Mannosidosis, run by Chiesi Farmaceutici S.p.A..
Trial summary
Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks. Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alpha-Mannosidosis
- What is being tested?
- Velmanase Alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 11 Jan 2021to 29 Dec 2021
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of alpha-mannosidosis based on alpha mannosidase activity <10% of normal in leukocytes or fibroblasts or through genetic testing;
- Capability to comply with the protocol;
- Evidence of informed consent provided by subject or legally authorized guardian(s) prior to performance of any trial-related activities.
Who cannot join
- Previous hematopoietic stem cells transplantation (HSCT) with positive outcome;
- Major surgery planned within 3 months prior to study entry or planned during the study that, in the opinion of the Investigator, would preclude participation in the trial;
- Known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that would preclude participation in the study in the Investigator's judgment;
- Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) UNLESS they are willing to use highly effective birth control methods;
- Participation in other interventional trials testing investigational medicinal products (IMPs) within the last 6 months;
- Total IgE >800 IU/ml;
- Any hypersensitivity to velmanase alfa or its excipients that, in the judgment of the Investigator, places the subject at an increased risk for adverse reactions
- Clinically active infection and recent vaccinations (within the last month before screening).
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks.
Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions
Read the detailed description
A Screening visit (V1) will take place 7±3 days prior to randomization in order to give the subject enough time to consider their participation in the study, to plan the next visits including the long-stay visits at V2, V5 and V8 (long-stay visits as PK and certain tests are performed over more than one day), and to allow the clinic center to complete the evaluation of the eligibility criteria.
Upon confirmation of eligibility, subjects will be randomized to receive weekly i.v. administration of either velmanase alfa 1 mg/kg or placebo.
Thereafter, subjects will undergo weekly visits for administration of study treatment and safety data collection. Clinical, laboratory and functional assessments will be performed at the 4-weekly assessment visits with each subject undergoing a minimum of 8 assessment visits (V1 to V8).
- Conditions
- Alpha-Mannosidosis
- Being tested
- Velmanase Alfa, Placebo
- Keywords
- Alpha-Mannosidosis, velmanase alfa, alpha-mann, shaman, mannosidosis, alpha-mannosidasis
- Medical subject headings
- alpha-Mannosidosis, Mannosidase Deficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Velmanase AlfaDrug
infusion i.v. treatment
PlaceboDrug
infusion i.v. treatment
| Study group | Role | What they receive |
|---|---|---|
| Velmanase alfa | Experimental | Not described Receives: Drug: Velmanase Alfa |
| placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in concentration of serum oligosaccharides
To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Level of serum oligosaccharides;
Measured: 24 weeks (end of study)
Change in serum level of total immunoglobulin (Ig)G level
Efficacy of velmanase alfa compared with placebo in alpha mannosidosis subjects based on serum levels of total immunoglobulin (Ig)G after 24 weeks of velmanase alfa treatment
Measured: 24 weeks (end of study)
Secondary outcomes (11)
Change in Intracellular level of oligosaccharides in peripheral blood leukocytes
To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Intracellular level of oligosaccharides accumulated in peripheral blood leukocytes.
Measured: 24 weeks (end of study)
Change in serum IgG Subclasses
To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Subclasses of IgG;
Measured: 24 weeks (end of study)
Incidence of Infections
Change in number of infections requiring antibiotics and/or hospitalization and/or loss of school/working days
Measured: 24 weeks (end of study)
Assessment of PK parameter Maximum plasma Concentration [Cmax]
To collect additional data on Cmax profile following velmanase alfa treatment
Measured: 12 weeks
Assessment of PK parameter Maximum plasma Concentration [Cmax]
To collect additional data on Cmax profile following velmanase alfa treatment
Measured: 24 weeks (end of study)
Assessment of PK parameter Area Under the Curve [AUC]
To collect additional data on AUC profile following velmanase alfa treatment
Measured: 24 weeks (end of study)
Assessment of PK parameter Area Under the Curve [AUC]
To collect additional data on AUC profile following velmanase alfa treatment
Measured: 12 weeks
Assessment of PK parameter Elimination half-life [t1/2]
To collect additional data on t1/2 profile following velmanase alfa treatment
Measured: 12 weeks
Assessment of PK parameter Elimination half-life [t1/2]
To collect additional data on t1/2 profile following velmanase alfa treatment
Measured: 24 weeks (end of study)
Assessment of PK parameter trough concentration (Ctrough)
To collect additional data on Ctrough profile following velmanase alfa treatment
Measured: 12 weeks
Assessment of PK parameter trough concentration (Ctrough)
To collect additional data on Ctrough profile following velmanase alfa treatment
Measured: 24 weeks (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2019
- Study start11 Jan 2021 (estimated)
- Primary completion27 Oct 2021 (estimated)
- Study completion29 Dec 2021 (estimated)
Why it stopped: Big delay on study activation (approval procedures by IRBs, hospitals contract negotiation) and on enrolment deadline due to CoViD-19; Placebo stock expires November 2021 and new batch not be available for at least one year
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind, randomized 2:1 to either velmanase alfa:placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Harmatz, MD, Principal investigator, UCSF Benioff Children's Hospital Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04031066
- Sponsor's protocol ID
- CLI-LMZYMAA2-01
- Acronym
- SHAMAN
- Status last verified
- Dec 2020
- First submitted
- 17 Jul 2019
- Last updated
- 8 Dec 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
- ClinicalTrials.gov ID
- NCT04031066
- Acronym / sponsor ID
- SHAMAN / CLI-LMZYMAA2-01
- Conditions
- Alpha-Mannosidosis
- Keywords
- Alpha-Mannosidosis, velmanase alfa, alpha-mann, shaman, mannosidosis, alpha-mannosidasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Big delay on study activation (approval procedures by IRBs, hospitals contract negotiation) and on enrolment deadline due to CoViD-19; Placebo stock expires November 2021 and new batch not be available for at least one year
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Study start
- 11 Jan 2021 (estimated)
- Primary completion
- 27 Oct 2021 (estimated)
- Study completion
- 29 Dec 2021 (estimated)
- First posted
- 24 Jul 2019 (actual)
- 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.
Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks.
Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions
Detailed description
A Screening visit (V1) will take place 7±3 days prior to randomization in order to give the subject enough time to consider their participation in the study, to plan the next visits including the long-stay visits at V2, V5 and V8 (long-stay visits as PK and certain tests are performed over more than one day), and to allow the clinic center to complete the evaluation of the eligibility criteria.
Upon confirmation of eligibility, subjects will be randomized to receive weekly i.v. administration of either velmanase alfa 1 mg/kg or placebo.
Thereafter, subjects will undergo weekly visits for administration of study treatment and safety data collection. Clinical, laboratory and functional assessments will be performed at the 4-weekly assessment visits with each subject undergoing a minimum of 8 assessment visits (V1 to V8).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind, randomized 2:1 to either velmanase alfa:placebo
| Arm | Type | Receives |
|---|---|---|
| Velmanase alfa | Experimental | Drug: Velmanase Alfa |
| placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of alpha-mannosidosis based on alpha mannosidase activity <10% of normal in leukocytes or fibroblasts or through genetic testing;
- Capability to comply with the protocol;
- Evidence of informed consent provided by subject or legally authorized guardian(s) prior to performance of any trial-related activities.
Key exclusion criteria (8 listed)
- Previous hematopoietic stem cells transplantation (HSCT) with positive outcome;
- Major surgery planned within 3 months prior to study entry or planned during the study that, in the opinion of the Investigator, would preclude participation in the trial;
- Known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that would preclude participation in the study in the Investigator's judgment;
- Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) UNLESS they are willing to use highly effective birth control methods;
- Participation in other interventional trials testing investigational medicinal products (IMPs) within the last 6 months;
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 Alfainfusion i.v. treatment | Drug | Velmanase alfa |
| Placeboinfusion i.v. treatment | Drug | placebo |
Primary outcome
Change in concentration of serum oligosaccharides
Time frame: 24 weeks (end of study)
To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Level of serum oligosaccharides;
Change in serum level of total immunoglobulin (Ig)G level
Time frame: 24 weeks (end of study)
Efficacy of velmanase alfa compared with placebo in alpha mannosidosis subjects based on serum levels of total immunoglobulin (Ig)G after 24 weeks of velmanase alfa treatment
11 secondary outcomes
Change in Intracellular level of oligosaccharides in peripheral blood leukocytes
Time frame: 24 weeks (end of study)
Change in serum IgG Subclasses
Time frame: 24 weeks (end of study)
Incidence of Infections
Time frame: 24 weeks (end of study)
Assessment of PK parameter Maximum plasma Concentration [Cmax]
Time frame: 12 weeks
Assessment of PK parameter Maximum plasma Concentration [Cmax]
Time frame: 24 weeks (end of study)
Assessment of PK parameter Area Under the Curve [AUC]
Time frame: 24 weeks (end of study)
Assessment of PK parameter Area Under the Curve [AUC]
Time frame: 12 weeks
Assessment of PK parameter Elimination half-life [t1/2]
Time frame: 12 weeks
Assessment of PK parameter Elimination half-life [t1/2]
Time frame: 24 weeks (end of study)
Assessment of PK parameter trough concentration (Ctrough)
Time frame: 12 weeks
Assessment of PK parameter trough concentration (Ctrough)
Time frame: 24 weeks (end of study)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- 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.
Paul Harmatz, MD principal investigator
UCSF Benioff Children's Hospital Oakland
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Velmanase Alfa in people with Alpha-Mannosidosis, run by Chiesi Farmaceutici S.p.A..
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 3 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: withdrawn, as of the sponsor's last update on 8 Dec 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. 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 was withdrawn before enrolling participants, so there are no results.
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?
Change in concentration of serum oligosaccharides (time frame: 24 weeks (end of study)). 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?
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 8 Dec 2020.