A 6 month safety, tolerability, efficacy and pharmacokinetic study with ANF-Rho to treat patients with chronic neutropenia.

Chronic neutropenia patients who are eligible for participation will be screened and enrolled to received open-label ANF-Rho for a period of 6 months. Study participation will be separated into 2 periods, Induction (8 weeks) and Maintenance (16 weeks). Blood samples to measure neutrophil levels and biochemistry labs will be drawn throughout the study to monitor efficacy response and patient safety. Pharmacokinetic samples will be collected during both periods and questionnaires will be completed by the patient and investigator for bone pain, quality of life (QOL) and injection site reaction.

Inclusion Criteria:

1. Patients 1 years of age or older

2. Patients with established chronic neutropenia defined as Median Absolute Neutrophil Count (ANC) < 0.5 x 109/L (both with and without demonstrated genetic lesion) having an indication for treatment, including:

   Independent of hematological parameters, all patients with: Shwachman-Diamond syndrome (SDS), Barth's syndrome or other inherited diseases associated with neutropenia (exclude Glycogen Storage Disease 1b)

3. Patients on granulocyte-colony stimulating factor (GCSF) & PEG-GCSF treatment are still eligible to participate after a washout period of 7 days, after the stopping of the drug

4. Signed and dated informed written consent/assent by the patient/parent

5. Women of childbearing potential with a negative serum pregnancy test and using a reliable method of contraception during the study period. Male study participants also agreeing to use contraception for the study period.

Exclusion Criteria:

1. Evidence of chromosomal abnormalities, myelodysplasia, hematologic malignancy, aplastic anemia, systemic lupus erythematosus, or rheumatoid arthritis (Felty's syndrome) or if the neutropenia was drug-induced
2. Progressive malignant disease or malignancy history
3. Presence of macrophage activation syndrome before the diagnosis of neutropenia
4. Clinical Significant Abnormal Renal, Cardiac, Hepatic or Blood Coagulation disease.
5. Chronic infection such as hepatitis B virus (HBV), hepatitis C Virus (HCV) or Human immunodeficiency virus( HIV) or history of tuberculosis
6. Association with anemia, thrombocytopenia (low blood platelets) before the diagnosis of neutropenia.
7. Drug abuse, substance abuse, or alcohol abuse
8. Use of any other investigational drug at the time of enrollment, or within 5 half-lives prior to enrollment, whichever is longer
9. Patients unwilling and/or who are not capable of ensuring compliance with the provisions of the study protocol
10. Women who are pregnant or breastfeeding
11. Women of childbearing potential who do not use an approved method of birth control. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) is not acceptable
12. Patients with known DNA loss-of-function mutations in GCSFR and RUNX1 genes