Back to resultsANF-Rho in the Treatment of Chronic Neutropenia
Primary Purpose
Neutropenia, Severe Chronic
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ANF-Rho
Sponsored by
About this trial
This is an interventional treatment trial for Neutropenia, Severe Chronic
Eligibility Criteria
Inclusion Criteria:
- Patients 1 years of age or older
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)
- 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
- Signed and dated informed written consent/assent by the patient/parent
- 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:
- 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
- Progressive malignant disease or malignancy history
- Presence of macrophage activation syndrome before the diagnosis of neutropenia
- Clinical Significant Abnormal Renal, Cardiac, Hepatic or Blood Coagulation disease.
- Chronic infection such as hepatitis B virus (HBV), hepatitis C Virus (HCV) or Human immunodeficiency virus( HIV) or history of tuberculosis
- Association with anemia, thrombocytopenia (low blood platelets) before the diagnosis of neutropenia.
- Drug abuse, substance abuse, or alcohol abuse
- Use of any other investigational drug at the time of enrollment, or within 5 half-lives prior to enrollment, whichever is longer
- Patients unwilling and/or who are not capable of ensuring compliance with the provisions of the study protocol
- Women who are pregnant or breastfeeding
- 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
- Patients with known DNA loss-of-function mutations in GCSFR and RUNX1 genes
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ANF-Rho
Arm Description
pegfilgrastim Anti-Neutropenic Factor (ANF)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Serum concentration of ANF-Rho over time
Pharmacokinetic parameter measuring ANF-Rho levels over time
The peak plasma concentration of ANF-Rho after administration (Cmax) over time
Pharmacokinetic Parameter measuring ANF-Rho levels over time
Total ANF-Rho exposure (AUC)
Pharmacokinetic parameter measuring ANF-Rho levels from time 0 through last dose.
Time to peak plasma concentration of ANF-Rho (Tmax)
Pharmacokinetic parameter measuring the time to Cmax.
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
Rate of subject reported infection related morbidities (infections, hospitalisations and antibiotic use) in Chronic Neutropenia patients treated with ANF Rho
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02533362
Brief Title
ANF-Rho in the Treatment of Chronic Neutropenia
Official Title
A Phase 2, Open-Label, Single Center, Efficacy, Safety, Tolerability, and Pharmacokinetic Study of ANF-Rho™ in Patients With Chronic Neutropenia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Withdrawn
Study Start Date
October 2015 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
October 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prolong Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A 6 month safety, tolerability, efficacy and pharmacokinetic study with ANF-Rho to treat patients with chronic neutropenia.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neutropenia, Severe Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ANF-Rho
Arm Type
Experimental
Arm Description
pegfilgrastim Anti-Neutropenic Factor (ANF)
Intervention Type
Drug
Intervention Name(s)
ANF-Rho
Other Intervention Name(s)
pegfilgrastim ANF
Intervention Description
Pegylated version of recombinant human granulocyte-colony stimulating factor (G-CSF)
Primary Outcome Measure Information:
Title
Neutrophil response rate to ANF Rho following a 6 month treatment period (induction, stabilization and maintenance periods) in patients with Chronic Neutropenia.
Description
Median Absolute Neutrophil Count (ANC) of ≥1.0 x 109/L over the 6 months total treatment period
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Serum concentration of ANF-Rho over time
Description
Pharmacokinetic parameter measuring ANF-Rho levels over time
Time Frame
6 months
Title
The peak plasma concentration of ANF-Rho after administration (Cmax) over time
Description
Pharmacokinetic Parameter measuring ANF-Rho levels over time
Time Frame
6 months
Title
Total ANF-Rho exposure (AUC)
Description
Pharmacokinetic parameter measuring ANF-Rho levels from time 0 through last dose.
Time Frame
6 months
Title
Time to peak plasma concentration of ANF-Rho (Tmax)
Description
Pharmacokinetic parameter measuring the time to Cmax.
Time Frame
6 months
Title
Half-Life of ANF-Rho (T1/2)
Description
Pharmacokinetic parameter to measure the time required for the concentration of the drug to reach half of its original value
Time Frame
6 months
Title
Rate of subject reported infection related morbidities (infections, hospitalisations and antibiotic use) in Chronic Neutropenia patients treated with ANF Rho
Time Frame
6 months
Title
Evaluate the effect of ANF Rho on the Quality of Life and Bone Pain in Chronic Neutropenia patients.
Description
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
Time Frame
6 months
Title
Evaluate safety and tolerability of subcutaneous injections of ANF Rho in chronic neutropenia patients.
Description
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.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients 1 years of age or older
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)
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
Signed and dated informed written consent/assent by the patient/parent
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:
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
Progressive malignant disease or malignancy history
Presence of macrophage activation syndrome before the diagnosis of neutropenia
Clinical Significant Abnormal Renal, Cardiac, Hepatic or Blood Coagulation disease.
Chronic infection such as hepatitis B virus (HBV), hepatitis C Virus (HCV) or Human immunodeficiency virus( HIV) or history of tuberculosis
Association with anemia, thrombocytopenia (low blood platelets) before the diagnosis of neutropenia.
Drug abuse, substance abuse, or alcohol abuse
Use of any other investigational drug at the time of enrollment, or within 5 half-lives prior to enrollment, whichever is longer
Patients unwilling and/or who are not capable of ensuring compliance with the provisions of the study protocol
Women who are pregnant or breastfeeding
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
Patients with known DNA loss-of-function mutations in GCSFR and RUNX1 genes
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hemant Misra, PhD
Organizational Affiliation
Prolong Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
ANF-Rho in the Treatment of Chronic Neutropenia
We'll reach out to this number within 24 hrs