Inclusion Criteria:

• Participants between the ages of 18 (or the minimum country-specific age of consent if > 18) and 70 years, inclusive, at Screening.
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures.
• Diagnosis of Primary ITP. ITP must be diagnosed in accordance with established guidelines.
  • Ongoing ITP (platelet counts 12 months; AND
  • Persistent ITP (3 to 12 months) or Chronic ITP >12 months.
• BMI 17.5 to 40 kg/m^2 , and minimum weight > 40 kg (88 lbs).
• Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

• Bleeding event according to the WHO grading scale 30 ≥ 2 occurring ≤ 4 weeks prior to screen OR a current bleeding event that, in the opinion of the investigator, requires treatment with standard of care therapy OR require blood or blood products during screening.
• Splenectomy within 3 months of randomization or planned during the study duration.
• Have current or recent history of clinically significant, acute or chronic, severe, progressive, or uncontrolled renal, hepatic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, psychiatric, immunologic/rheumatologic or neurologic disease; or have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study intervention administration, or interfere with the interpretation of study results; or in the opinion of the investigator, the participant is inappropriate for entry into this study.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
• Contraindication for the pre and post medication treatments (NSAID, APAP, corticosteroids, antihistamine).
• Pregnant female participants; breastfeeding female subjects; and female participants of childbearing potential who are unwilling or unable to use one method of contraception as outlined in this protocol for the duration of the study and for at least 43 days after the last dose of study intervention.
• Have a history of alcohol or substance abuse within 12 months prior to Day 1 that in the opinion of the investigator will preclude participation in the study or protocol adherence in the study. A positive urine drug screen must be reflective of a clinically appropriate use.
• History of autoimmune disorders or other conditions that compromise or impair the immune system (including but not limited to: CD, RA, scleroderma, vasculitis, SLE, Grave’s disease or asthma) or a current positive test for the following: rheumatoid factor, or anti-nuclear antibody, or anti-double strand DNA.
•  Co-existing myelodysplastic disorder. If clinically significant anemia, neutropenia, or pancytopenia exists, documentation of a bone marrow aspirate/biopsy within 24 months prior to the first study dose showing no evidence of myelodysplasia is required.
• Co-existing thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, coagulopathies or other bleeding disorders.
• History of immune deficiency or current evidence of total IgG or total IgA deficiency.
• History of allergic or anaphylactic reaction to any components of the study intervention.
• Have cancer or a history of cancer within 5 years of screening (other than adequately resected cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence within the previous 3 years).
• Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria:
  • Suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the C-SSRS;
  • Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS;
  • Any lifetime history of serious or recurrent suicidal behavior.
• Current use of any prohibited concomitant medication(s) or those unwilling/unable to use a permitted concomitant medication(s).
• Any prior treatment with rituximab (or any other B cell depleting agent) must have been completed and eligibility requires a normal CD19 count (> 100 cells per microliter) for 12 months prior to first dose.
• Recent high doses corticosteroids (> 20 mg prednisone or equivalent per day). If on corticosteroids, must be on a stable dose for ≥ 8 days prior to the first dose (maximum dose up to 20 mg/day prednisone equivalent) and expected to remain on a stable dose throughout the study. 
• Treatment with IVIg ≤ 28 days prior to the first dose.
• Treatment with plasmapheresis within 3 months prior to the first dose.
• Treatment with an anti-Rh D antigen agent (e.g., WinRho®) ≤ 28 days prior to the first dose.
• If receiving avotrombopag, eltrombopag, fostamatinib, or romiplostim, the dose must have been stable for ≥ 28 days prior to the first dose of study intervention and must be expected to remain stable throughout the study.
• If receiving adjunct immunosuppressants such as cyclosporine, azathioprine, mycophenolate, or 6-mercaptopurine, the doses must be stable for 2 months prior to day 1 and anticipated to remain stable throughout the study. Stable dosages should not exceed MMF 3 g/day; AZA 2 mg/kg/day and cyclosporine 5 mg/kg/day. 
• Treatment with other cytotoxic agents (eg, cyclophosphamide, vincristine) is not allowed within 3 months prior to the first dose.
• Use of any systemic treatment or herbal supplement that is known to affect platelets (i.e., resveratrol).
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Renal impairment eGFR < 60.
• Presence of any of the following laboratory abnormalities at Screening:
  • B-cell count below the LLN, defined as 100 cells/µL (obtained from CLIA certified central lab);
  • Total serum IgG 2.0 × ULN;
  • Total bilirubin level > 1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is < ULN;
  • Any abnormality consistent with or suggestive of coagulopathy (d-dimer, fibrinogen, PTT, INR);
  • Serum creatinine > 1.5 x ULN or eGFR 160 mmHg and/or diastolic blood pressure > 95 mmHg).
• Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (e.g., QTcF interval > 450 msec, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is > 450 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant’s eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
• Evidence of active infection, including suspected or laboratory confirmed SARS-COVID-19 virus less than 14 days prior to first dose of study intervention.
• Have active acute or chronic infection requiring treatment or suppression with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1.
  • NOTE: rescreen is allowed one time after resolution of infection.
• Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1.
  • NOTE: rescreen is allowed one time after resolution of infection.
• Abnormal findings on the screening chest radiographs (e.g., chest X-ray) including, but not limited to, presence of TB, general infections, heart failure, or malignancy. Chest radiographs examination may be performed up to 12 weeks prior to Day 1. Documentation of the official reading must be available in the source documentation.
• Herpes infection meeting at least one of the following criteria:
  • A herpes zoster episode 3 months prior to Screening;
  • History of recurrent (i.e., more than one episode) herpes zoster;
  • History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
• Scheduled or anticipated invasive procedures within 28 days from Day 1 (e.g,, surgery, dental procedures) throughout the study and follow up period.
• Having received any live vaccine within 3 months or non-live vaccine within 1 month prior to the first dose and throughout the study and follow up. An approved COVID-19 vaccine is considered a concomitant medication. Due to the potential for interference with vaccine efficacy, the last dose of an approved COVID-19 vaccine must be completed 28 days prior to dosing with PF-06835375.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention (whichever is longer).
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.