ANF-Rho in the Treatment of Chronic Neutropenia

A Phase 2, Open-Label, Single Center, Efficacy, Safety, Tolerability, and Pharmacokinetic Study of ANF-Rho™ in Patients With Chronic Neutropenia

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

Study Overview

• Status: Withdrawn
• Conditions: Neutropenia, Severe Chronic
• Intervention / Treatment: Drug: ANF-Rho

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANF-Rho; pegfilgrastim Anti-Neutropenic Factor (ANF)	Drug: ANF-Rho; Pegylated version of recombinant human granulocyte-colony stimulating factor (G-CSF); Other Names: pegfilgrastim ANF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil response rate to ANF Rho following a 6 month treatment period (induction, stabilization and maintenance periods) in patients with Chronic Neutropenia.	Median Absolute Neutrophil Count (ANC) of ≥1.0 x 109/L over the 6 months total treatment period	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of ANF-Rho over time	Pharmacokinetic parameter measuring ANF-Rho levels over time	6 months
The peak plasma concentration of ANF-Rho after administration (Cmax) over time	Pharmacokinetic Parameter measuring ANF-Rho levels over time	6 months
Total ANF-Rho exposure (AUC)	Pharmacokinetic parameter measuring ANF-Rho levels from time 0 through last dose.	6 months
Time to peak plasma concentration of ANF-Rho (Tmax)	Pharmacokinetic parameter measuring the time to Cmax.	6 months
Half-Life of ANF-Rho (T1/2)	Pharmacokinetic parameter to measure the time required for the concentration of the drug to reach half of its original value	6 months
Rate of subject reported infection related morbidities (infections, hospitalisations and antibiotic use) in Chronic Neutropenia patients treated with ANF Rho		6 months
Evaluate the effect of ANF Rho on the Quality of Life and Bone Pain in Chronic Neutropenia patients.	Change in Quality of life over 6 months measured by the Short Form 36, change in bone pain over 6 months measured by the Bone Pain Questionnaire, Wong and Baker Scale and FLACC Behavioral Pain Assessment Scale	6 months
Evaluate safety and tolerability of subcutaneous injections of ANF Rho in chronic neutropenia patients.	Composite endpoint with multiple vital signs, bone scans, biopsies, splenic ultrasounds, electrocardiographic assessments, clinical signs, and bio-analytical measures (e.g., biochemistry), and reported adverse events following repeated dosing.	6 months

Collaborators and Investigators

• Sponsor: Prolong Pharmaceuticals
• Investigators: Study Director: Hemant Misra, PhD, Prolong Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: August 10, 2015
• First Submitted That Met QC Criteria: August 25, 2015
• First Posted (Estimate): August 26, 2015

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 4, 2019
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia
• Other Study ID Numbers: PGCN-002