A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002
This is a Phase 1 study to investigate the safety and tolerability of AK002 in patients with
 indolent systemic mastocytosis (ISM).
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)