A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis

Alpha-Mannosidosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01681953
• Other study ID #: rhLAMAN-05
• Secondary ID: 2012-000979-17
• Status: Completed
• Phase: Phase 3
• Start date: August 2012
• Est. completion date: May 2014

Study information

• Verified date: July 2020
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 35 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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)

Related Conditions & MeSH terms

• Alpha-Mannosidosis

Intervention

Drug:
• Lamazym
ERT, i.v. infusions weekly
• Placebo
Infusions weekly

Locations

Country	Name	City	State
Denmark	Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9	Copenhagen
France	Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel	Bron
France	Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter	PARIS Cedex 12
Germany	Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1	Mainz
Poland	The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20	Warszawa
United Kingdom	Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Zymenex A/S	European Commission

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Poland,  United Kingdom, 

References & Publications (4)

Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigò 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 — View Citation

Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen Ø, 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. — View Citation

Borgwardt 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. — View Citation

Harmatz P, Cattaneo F, Ardigò 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quantitative determination of rhLAMAN in plasma	Pharmacokinetic (PK) assessments. Blood samples are drawn pre-treatment and at various times post-treatment (see time frame above)	10 min, 60 min, 2 hours, 24 hours, 3 days, 7 days
Primary	Reduction of oligosaccharides in serum	Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group	Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Primary	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	Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Secondary	Forced Vital Capacity	Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group	Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Secondary	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	Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Secondary	Adverse Events	Safety endpoint assessed weekly throughout the trial	1 week
Secondary	Development of clinically significant changes in vital signs and change in physical examination	Safety endpoints assessed weekly throughout the trial	1 week
Secondary	Clinical laboratory parameters (hematology, biochemistry and urinalysis)	Safety endpoints assessed weekly throughout the trial	1 week
Secondary	Development of Lamazym antibodies and neutralizing/inhibitory antibodies	Safety endpoints assessed weekly throughout the trial	1 week

External Links

•   Study Record on EU Clinical Trials Register including results