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

NCT01681953 | Completed Phase 3 DMC

• 2 other identifiers: rhLAMAN-052012-000979-17
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 6

Brief 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

Conditions

Alpha-Mannosidosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Forced Vital Capacity

  Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

• The distance walked in 6 minutes (6-minute walk test)

  Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

• Adverse Events

  1 week

• Development of clinically significant changes in vital signs and change in physical examination

  1 week

• Clinical laboratory parameters (hematology, biochemistry and urinalysis)

  1 week

Other Outcomes (1)

• Quantitative determination of rhLAMAN in plasma

  10 min, 60 min, 2 hours, 24 hours, 3 days, 7 days

Study Arms (2)

Lamazym

ACTIVE COMPARATOR

1 mg Lamazym/kg body weight

Drug: Lamazym

Placebo

PLACEBO COMPARATOR

Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol

Drug: Placebo

Interventions

Lamazym DRUG

ERT, i.v. infusions weekly

Also known as: rhLAMAN, recombinant human alpha-mannosidase

Lamazym

Placebo DRUG

Infusions weekly

Placebo

Eligibility Criteria

• Age: 5 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Zymenex A/S: lead
• European Commission: collaborator

Study Sites (6)

Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9

Copenhagen, DK-2100, Denmark

Location

Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel

Bron, 69677, France

Location

Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter

Paris, 75 571, France

Location

Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1

Mainz, 55131, Germany

Location

The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20

Warsaw, 04 730, Poland

Location

Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,

Manchester, M13 9WL, United Kingdom

Location

Related Publications (4)

• Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, 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.

  PMID: 26048034 BACKGROUND

• 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.

  PMID: 26016802 BACKGROUND

• Harmatz P, Cattaneo F, Ardigo 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.

  PMID: 29716835 BACKGROUND

• Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigo 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 patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0. Epub 2018 May 30.

  PMID: 29846843 RESULT

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

alpha-Mannosidosis

Condition Hierarchy (Ancestors)

Mannosidase Deficiency Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Allan M Lund, MD

  Copenhagen University Hospital, Center for Metabolic Diseases, Department for Clinical Genetics

  PRINCIPAL INVESTIGATOR

• Jens Fogh

  Zymenex A/S

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2012
• First Posted: September 10, 2012
• Study Start: August 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

FR (2); PL (1); DE (1); GB (1); DK (1)