A long-term safety trial of repeated Velmanase Alfa treatment of subjects with Alpha-Mannosidosis

• Register: EUCTR
• Last refreshed on: 9 January 2023
• Main ID: EUCTR2013-000321-31-DK
• Date of registration: 07/06/2013
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A long-term safety trial of repeated Velmanase Alfa treatment of subjects with Alpha-Mannosidosis
• Scientific title: A multi-center, un-controlled, open-labeled trial of the long-term safety of Velmanase Alfa aftercare treatment of subjects with alpha-Mannosidosis whom previously participated in Velmanase Alfa - trials - Phase IIIb
• Date of first enrolment: 07/06/2013
• Target sample size: 8
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000321-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Denmark, Poland

Contacts

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatement of Alpha-Mannosidosis
MedDRA version: 20.0 Level: LLT Classification code 10032658 Term: Other specified disorders of carbohydrate transport and metabolism System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Velmanase Alfa
Product Code: rhLAMAN
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: velmanase alfa
CAS Number: 1492823-75-2
Current Sponsor code: rhLAMAN
Other descriptive name: recombinant human alpha-mannosidase
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

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)

Main Objective: 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.

Secondary Objective: Not applicable

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.

Secondary Outcome(s)

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.

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

Secondary ID(s)

2013-000321-31

rhLAMAN-09

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A

Ethics review

Status: Approved
Approval date: 28/05/2013
Contact: