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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002

Primary Purpose

Indolent Systemic Mastocytosis

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
AK002
Sponsored by
Allakos Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Indolent Systemic Mastocytosis focused on measuring ISM, Mastocytosis, Indolent Mastocytosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Provided written informed consent
  2. Male or female aged ≥18 and ≤65 years at the time of signing the informed consent form
  3. Confirmed diagnosis of ISM based on World Health Organization (WHO) criteria (Appendix 1)
  4. Presence of at least 1 of the following SM related symptoms:

    1. Flushing (at least 1 episode per week)
    2. Pruritus (minimum MAS2 score of 4) (Appendix 2)
    3. Diarrhea (minimum MAS2 score of 4) (Appendix 2)
    4. Anaphylaxis (at least 1 episode [grade 2 or higher] within the last 12 months)
  5. Serum total tryptase exceeded 15 ng/mL* at 2 or more measurements obtained 1 or more months apart within the last 2 years (*Note: this varies from the minor criterion of "persistently exceeds 20 ng/mL" in the WHO criteria for diagnosis of ISM)
  6. Willing and able to comply with the study procedures and visit schedule, including follow-up visits
  7. Able to communicate effectively with the study site personnel
  8. Negative Screening urine drug tests (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, methaqualone, opiates, phencyclidine)
  9. Negative Screening ova and parasite test
  10. Determined by the Investigator to be in good health as documented by the medical history, physical examination (PE), vital sign assessments, 12- lead ECG, clinical laboratory assessments, and by general observations
  11. Women of child bearing potential, must be using highly effective methods of birth control (failure rate <1% per year when used consistently and correctly) at least 4 weeks prior to Screening until Day 85. Women should be informed of the potential risks associated with becoming pregnant while enrolled. Accepted forms of contraception are implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs). In addition, a barrier method must always be used concomitantly to the highly effective method. Double-barrier is not considered a highly effective method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not an acceptable means of contraception. Female patients are considered to not be of child-bearing potential when they are post-menopausal for at least 2 years with follicle-stimulating hormone (FSH) levels >40 mIU/mL, are surgically sterilized, or have undergone hysterectomy.
  12. Male patients with female partners of childbearing potential must agree to use a condom without spermicide during sexual activity with female partners of childbearing potential. Female sexual partners of male patients must be willing to avoid pregnancy according to the above described methods.

Exclusion Criteria:

  1. Known hypersensitivity to any constituent of the study drug
  2. Presence of an associated hematologic non-mast-cell lineage disorder or MC leukemia
  3. Any disease or condition (medical or surgical) which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of AK002, or would place the patient at increased risk
  4. The presence of abnormal laboratory values considered to be clinically significant by the Investigator
  5. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to administration of study drug (90 days or 5 half-lives, whichever is longer, for biologic products)
  6. Treatment with chemotherapy or radiotherapy in the preceding 6 months
  7. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening
  8. Use during the 7 days before Screening (or 5 half-lives, whichever is longer) or expected to require the use of angiotensin converting enzyme (ACE) inhibitors or beta blockers
  9. Use during the 30 days before Screening (or 5 half lives, whichever is longer) or expected to require the use of omalizumab, immunosuppressive drugs, or systemic corticosteroids with a daily dose >10 mg prednisone or equivalent
  10. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of the study drug administration
  11. Donation or loss of >500 mL of blood within 56 days prior to administration of study drug or donation of plasma within 7 days prior to administration of study drug
  12. Has not refrained from excessive caffeine consumption (>3 cups of coffee per day or equivalent) for 48 hours prior to study drug administration and agreed to this do so throughout the inpatient period
  13. Positive hepatitis serology results, except for vaccinated patients or patients with past but resolved hepatitis, at Screening
  14. Positive HIV serology results at Screening
  15. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment
  16. Patient is vulnerable (e.g., patient kept in detention)

Sites / Locations

  • Charité - Universitätsmedizin Berlin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AK002

Arm Description

IV dose of AK002

Outcomes

Primary Outcome Measures

To evaluate the safety and tolerability by evaluating Clinical laboratory parameters and adverse events assessed using the CTCAE version 4

Secondary Outcome Measures

Evaluate PK of AK002 in patients with ISM
Evaluate the change from baseline in absolute peripheral counts of eosinophils and basophils.
Evaluate the change from baseline in serum tryptase and eosinophil grande protein levels.
Measure changes form baseline in the 24-hour urine histamine metabolites.
Mastocytosis Quality of Life Questionnaire

Full Information

First Posted
June 16, 2016
Last Updated
March 12, 2019
Sponsor
Allakos Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02808793
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002
Official Title
A Phase 1, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002 in Patients With Indolent Systemic Mastocytosis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 2016 (Actual)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allakos Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 1 study to investigate the safety and tolerability of AK002 in patients with indolent systemic mastocytosis (ISM).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Systemic Mastocytosis
Keywords
ISM, Mastocytosis, Indolent Mastocytosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AK002
Arm Type
Experimental
Arm Description
IV dose of AK002
Intervention Type
Drug
Intervention Name(s)
AK002
Primary Outcome Measure Information:
Title
To evaluate the safety and tolerability by evaluating Clinical laboratory parameters and adverse events assessed using the CTCAE version 4
Time Frame
From study start to Day 85 or early term visit
Secondary Outcome Measure Information:
Title
Evaluate PK of AK002 in patients with ISM
Time Frame
Through out the study from baseline to Day 85 or early term visit
Title
Evaluate the change from baseline in absolute peripheral counts of eosinophils and basophils.
Time Frame
Through out the study from screening to Day 85 or early term visit
Title
Evaluate the change from baseline in serum tryptase and eosinophil grande protein levels.
Time Frame
Through out the study from screening to Day 29 or early term visit
Title
Measure changes form baseline in the 24-hour urine histamine metabolites.
Time Frame
Starting pre dose on day -1 to days 1, 3 and 4
Title
Mastocytosis Quality of Life Questionnaire
Time Frame
Through out the study from screening to Day 85 or early term visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provided written informed consent Male or female aged ≥18 and ≤65 years at the time of signing the informed consent form Confirmed diagnosis of ISM based on World Health Organization (WHO) criteria (Appendix 1) Presence of at least 1 of the following SM related symptoms: Flushing (at least 1 episode per week) Pruritus (minimum MAS2 score of 4) (Appendix 2) Diarrhea (minimum MAS2 score of 4) (Appendix 2) Anaphylaxis (at least 1 episode [grade 2 or higher] within the last 12 months) Serum total tryptase exceeded 15 ng/mL* at 2 or more measurements obtained 1 or more months apart within the last 2 years (*Note: this varies from the minor criterion of "persistently exceeds 20 ng/mL" in the WHO criteria for diagnosis of ISM) Willing and able to comply with the study procedures and visit schedule, including follow-up visits Able to communicate effectively with the study site personnel Negative Screening urine drug tests (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, methaqualone, opiates, phencyclidine) Negative Screening ova and parasite test Determined by the Investigator to be in good health as documented by the medical history, physical examination (PE), vital sign assessments, 12- lead ECG, clinical laboratory assessments, and by general observations Women of child bearing potential, must be using highly effective methods of birth control (failure rate <1% per year when used consistently and correctly) at least 4 weeks prior to Screening until Day 85. Women should be informed of the potential risks associated with becoming pregnant while enrolled. Accepted forms of contraception are implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs). In addition, a barrier method must always be used concomitantly to the highly effective method. Double-barrier is not considered a highly effective method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not an acceptable means of contraception. Female patients are considered to not be of child-bearing potential when they are post-menopausal for at least 2 years with follicle-stimulating hormone (FSH) levels >40 mIU/mL, are surgically sterilized, or have undergone hysterectomy. Male patients with female partners of childbearing potential must agree to use a condom without spermicide during sexual activity with female partners of childbearing potential. Female sexual partners of male patients must be willing to avoid pregnancy according to the above described methods. Exclusion Criteria: Known hypersensitivity to any constituent of the study drug Presence of an associated hematologic non-mast-cell lineage disorder or MC leukemia Any disease or condition (medical or surgical) which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of AK002, or would place the patient at increased risk The presence of abnormal laboratory values considered to be clinically significant by the Investigator Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to administration of study drug (90 days or 5 half-lives, whichever is longer, for biologic products) Treatment with chemotherapy or radiotherapy in the preceding 6 months Treatment for a clinically significant helminthic parasitic infection within 6 months of screening Use during the 7 days before Screening (or 5 half-lives, whichever is longer) or expected to require the use of angiotensin converting enzyme (ACE) inhibitors or beta blockers Use during the 30 days before Screening (or 5 half lives, whichever is longer) or expected to require the use of omalizumab, immunosuppressive drugs, or systemic corticosteroids with a daily dose >10 mg prednisone or equivalent Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of the study drug administration Donation or loss of >500 mL of blood within 56 days prior to administration of study drug or donation of plasma within 7 days prior to administration of study drug Has not refrained from excessive caffeine consumption (>3 cups of coffee per day or equivalent) for 48 hours prior to study drug administration and agreed to this do so throughout the inpatient period Positive hepatitis serology results, except for vaccinated patients or patients with past but resolved hepatitis, at Screening Positive HIV serology results at Screening Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment Patient is vulnerable (e.g., patient kept in detention)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus Maurer, MD
Organizational Affiliation
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002

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