Clinical Trial of Ambroxol in Patients With Type I Gaucher Disease

This is an Open-Label, Dose Escalation with 2 Dose Levels, Proof-of-Concept Clinical Trial
of Ambroxol for the Treatment of Patients with Type I Gaucher Disease.

This study is a randomized clinical trial involving 20 evaluable patients affected with Type
1 Gaucher disease who are responsive to Ambroxol in vitro. There are 2 treatment groups,
involving 2 dose levels of Ambroxol (187.5 and 225 mg/day), given once daily PO for 2 months
in both groups. The 187.5-mg/day dose level will be tested first. If there are no
significant adverse events, defined as >Grade 3 toxicity according to the latest version of
the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), the 225-mg/day dose
level will be tested.

Inclusion Criteria:

- Biochemically and genetically confirmed diagnosis of Gaucher disease caused by
β-glucocerebrosidase deficiency resulting from mutations in the GBA genes, which have
been shown to respond to Ambroxol according to in vitro screening assay.

- Must be 16 years of age or older at the time of study initiation.

- With an intact, enlarged spleen.

- A hemoglobin level of at least 10 g/L.

- Able to understand and cooperate with the requirements of the study protocol.

- Mentally competent, have ability to understand and willingness to sign the informed
consent form.

- Able to travel to a participating study site.

- Women of child-bearing potential must use accepted contraceptive methods, and must
have a negative serum or urine pregnancy test within one week prior to treatment
initiation. An additional pregnancy test is to be performed, and results obtained,
prior to administration of the first dose of Ambroxol.

- Fertile men must practice effective contraceptive methods during the study period,
unless documentation of infertility exists.

- Body weight >40 kg (88 lbs).

Exclusion Criteria:

- Receipt of any form of glucocerebrosidase <<4 weeks prior study initiation.

- Total splenectomy.

- Serious medical illness, significant cardiac disease, chronic bronchitis, emphysema,
and cystic fibrosis, as well as disorders causing ventilation perfusion mismatch.

- Substance abuse.

- Any complex disease that may confound treatment assessment.

- Pregnant women, or women of child-bearing potential not using reliable means of
contraception.

- Lactating females because of the potential for adverse reactions in nursing infants.

- Fertile men unwilling to practice contraceptive methods during the study period.

- Unwilling or unable to follow protocol requirements.

- Known hypersensitivity reactions, intolerance or adverse reactions to Ambroxol or to
the inactive ingredients.

- Evidence of systemic infection, or serious infection within the past month.

- Known to have HIV infection.

- Known to have hepatitis B or hepatitis C.

- Patients with a history of convulsive disorders.

- Patients receiving any other investigational treatment for any indication within the
past 4 weeks prior to initiation of Ambroxol treatment.

- A history of cancer of any type.

- Patients who have received immunotherapy of any type within the past 4 weeks prior to
study initiation.

- Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of patients.