E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatement of Alpha-Mannosidosis |
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E.1.1.1 | Medical condition in easily understood language |
Treatement of Alpha-Mannosidosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10032658 |
E.1.2 | Term | Other specified disorders of carbohydrate transport and metabolism |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective of this trial is to provide aftercare treatment with Velmanase- Alfa and to evaluate the safety and efficacy of repeated Velmanase- Alfa i.v. treatment of subjects with alpha-Mannosidosis whom previously participated in Velmanase- Alfa -trial. This protocol only concern subjects, where compassionate use program was not accepted (OR NO PHYSICIAN COULD BE IDENTIFIED) Efficacy will be evaluated once yearly to follow the subject’s progress in clinical parameters and at one additional comprehensive evaluation visit (2500) to evaluate additional efficacy parameters. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject must have participated in previous Velmanase- Alfa -trials: phase 2b: 2011-004355-40, phase 3: 2012-000979-17 or phase 2 2016-001988-36 2. Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities 3. The subject and his/her guardian(s) must have the ability to comply with the protocol
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E.4 | Principal exclusion criteria |
1. 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 2. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial 3. Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and evaluate with the patients and/or parents whether or not there is a need for contraception. 4. Psychosis; any psychotic disease, also in remission, is an exclusion criteria 5. Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
All endpoints are evaluated as change from baseline (pre-treatment in the subject’s original Velmanase- Alfa trial). Safety Endpoints: • Adverse events (AEs) • Vital signs and change in physical examination • Development of Velmanase- Alfa antibodies and neutralizing/inhibitory antibodies • Clinical laboratory parameters (hematology, biochemistry, IgG, IgA, IgM and urinalysis)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety will be assessed at every visit. Development of antibodies are measured every 12th week Serum Oligosaccarides will be evaluated every 6th months. |
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E.5.2 | Secondary end point(s) |
All endpoints are evaluated as change from baseline (pre-treatment in the subject’s original Velmanase- Alfa trial). The Efficacy endpoints of the trial are evaluation of: o Oligosaccharides in serum o Motor proficiency (BOT-2) o Three minute stair climb test (3MSCT) o Leiter R o Forced Vital Capacity (FVC) o Six minute walk test (6MWT) o Pure tone Audiometry o Questionnaires CNS parameters (visit 2500 only): o Assessment of mannose-rich oligosaccharides in brain tissue as measured by MRS visual score (for patients who previously participated in rhLAMAN-02), MRI diffusion coefficient in white matter, gray matter and centrum semi oval o Cerebrospinal fluid neuro-degeneration biomarker (Tau, NFL, GFAp) o Oligosaccharides in CSF Other laboratory parameters (visit 2500 only): o Plasma PK profile o Oligosaccharides in 24-h urine collection o Measurement of in vivo biological activity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy will be assessed yearly, counted from the latest evaluation in the subject's previous Velmanase- Alfa trial, and at one additional comprehensive evaluation visit (2500) to evaluate additional efficacy parameters. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |