PF-06835375 for Low Platelet Count

Recruiting at 37 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Disqualifiers: Recent bleeding, Splenectomy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12-16 weeks

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a new injectable medicine called PF-06835375. It targets adults with long-lasting or chronic low platelet counts due to primary immune thrombocytopenia (ITP). The medicine works by reducing specific immune cells to help increase platelet counts.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What evidence supports the effectiveness of the drug PF-06835375 for low platelet count?

The research mentions that thrombopoietin and its analogues, which are similar to PF-06835375, have been shown to be potent stimulators of platelet production and can enhance platelet recovery after chemotherapy. Additionally, other thrombopoietin receptor agonists like romiplostim and avatrombopag have been effective in increasing platelet counts in patients with immune thrombocytopenia. ^{1 2 3 4 5}

How is the drug PF-06835375 different from other treatments for low platelet count?

There is no specific information available about PF-06835375 in the provided research articles, so its unique features compared to other treatments for low platelet count cannot be determined from this data. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with primary immune thrombocytopenia (ITP) who have had low platelet counts for more than 3 months. They shouldn't have had severe bleeding in the last month or need blood products during screening, and they can't join if they've had a splenectomy within the past 3 months or plan to have one.

Inclusion Criteria

I have been diagnosed with ITP and my platelet count is below 50, without severe bleeding in the last month.

Exclusion Criteria

I have had a significant bleeding event recently or need treatment for current bleeding.

I have had my spleen removed recently or will have it removed soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of PF-06835375 once monthly. Cohort 1 receives treatment for 3 months, while cohorts 2 and 3 receive treatment for 4 months.

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on changes in platelet counts.

4 weeks

Treatment Details

Interventions

• PF-06835375

Trial Overview The study tests PF-06835375 through multiple subcutaneous injections to see if it's safe and effective for treating ITP. It's an open-label Phase 2 trial, meaning both researchers and participants know what treatment is being given.

Participant Groups

Group I: Open Label PF-06835375 dose 3 Treatment Experimental Treatment 1 Intervention

subcutaneous injection once monthly for 4 months

Group II: Open Label PF-06835375 dose 2 Treatment Experimental Treatment 1 Intervention

subcutaneous injection once monthly for 4 months

Group III: Open Label PF-06835375 dose 1 Treatment Experimental Treatment 1 Intervention

subcutaneous injection once monthly for 3 months

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Interleukin-11 has been approved by the FDA for reducing severe thrombocytopenia in patients undergoing intensive chemotherapy, demonstrating its efficacy in this specific context.

While thrombopoietin and its analogues are potent stimulators of platelet production with few side effects, their effectiveness in preventing severe thrombocytopenia during leukemia treatment and bone marrow transplants has been disappointing, and some can induce harmful antibodies that lead to thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical biology and potential use of thrombopoietin. Basser, R.[2019]

In a 52-week study involving 234 adults with immune thrombocytopenia, romiplostim significantly increased the rate of platelet response compared to standard care, with a response rate 2.3 times higher (P<0.001).

Patients receiving romiplostim experienced fewer treatment failures and required splenectomy less often (11% vs. 30% for standard care, P<0.001), along with lower rates of bleeding events and improved quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim or standard of care in patients with immune thrombocytopenia. Kuter, DJ., Rummel, M., Boccia, R., et al.[2016]

In a 6-month Phase 3 study involving 49 adults with chronic immune thrombocytopenia (ITP), avatrombopag (20 mg/day) significantly improved platelet counts compared to placebo, with a median cumulative number of weeks of platelet response of 12.4 weeks versus 0 weeks for placebo (P < 0.0001).

Avatrombopag also demonstrated a higher platelet response rate at day 8 (65.63% vs. 0.0% for placebo, P < 0.0001) and reduced the need for concomitant ITP medications, while maintaining a safety profile similar to earlier studies, with common side effects being headache and contusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Jurczak, W., Chojnowski, K., Mayer, J., et al.[2019]

New thrombopoietic factors have shown promise in increasing platelet counts and reducing the severity of therapy-induced thrombocytopenia in preclinical models and early patient trials, but clinical benefits are not yet fully established.

Ongoing studies are examining the use of these factors in various clinical settings, including patients with acute myeloid leukemia and those undergoing stem cell transplantation, while also addressing potential methodologic issues and monitoring for side effects, especially in normal donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities for the use of thrombopoietic growth factors. Schiffer, CA.[2005]

New generation thrombopoietic growth factors, like romiplostim and eltrombopag, effectively increase platelet counts in patients with immune thrombocytopenic purpura (ITP), showing response rates above 70-80% even in those who have failed previous treatments.

These agents work by increasing platelet production rather than reducing consumption, but their long-term safety is not fully understood, leading to recommendations for their use primarily in refractory cases or before splenectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic immune thrombocytopenic purpura. New agents. Rodeghiero, F., Ruggeri, M.[2016]

XR300, a new nonpeptide GPIIb/IIIa antagonist, shows strong antiplatelet effects by inhibiting platelet aggregation and fibrinogen binding, with very low effective concentrations (IC50 values of 0.09 microM and 0.01 microM respectively).

In animal studies, XR300 demonstrated rapid and prolonged antithrombotic effects, effectively preventing thrombosis in models of arterial injury, indicating its potential as a more effective therapy compared to currently used antiplatelet drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous and oral antiplatelet/antithrombotic efficacy and specificity of XR300, a novel nonpeptide platelet GPIIb/IIIa antagonist. Mousa, SA., Forsythe, M., Wityak, J., et al.[2019]

KF4939 is a new oral medication that effectively inhibits platelet aggregation in both laboratory settings and in live animals, showing promise for preventing blood clots.

It works through a unique mechanism that differs from traditional cyclooxygenase inhibitors, making it effective against various types of platelet activation, including those induced by collagen, ADP, and thrombin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of platelet aggregation by a new agent, 2,2'-dithiobis-(N-2-hydroxypropyl benzamide) (KF4939). Yamada, K., Shuto, K., Nakamizo, N.[2019]

SK&F 106760 is a potent GPIIb/IIIa antagonist that effectively inhibits platelet aggregation in conscious dogs, achieving complete inhibition for varying durations based on the dose administered (0.3-3 mg/kg).

The drug demonstrated a favorable pharmacokinetic profile with a short initial half-life of 11 minutes followed by a longer elimination phase of 66 minutes, indicating it can maintain effective plasma levels for a significant duration after intravenous administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The in vivo pharmacological profile of the novel glycoprotein IIb/IIIa antagonist, SK&F 106760. Nichols, AJ., Vasko, JA., Koster, PF., et al.[2003]

The novel PAF antagonist SR 27417 effectively inhibits platelet aggregation in rabbits for at least 3 days after a single oral dose of 5 mg/kg, demonstrating a strong and lasting effect.

The mechanism of action involves both competitive inhibition shortly after intravenous administration and non-competitive inhibition 24 hours after oral administration, indicating a complex interaction with PAF binding sites on platelets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo effects of SR 27417, a novel PAF antagonist, on rabbit platelet aggregation and [3H]-PAF binding. Herbert, JM., Laplace, MC., Maffrand, JP.[2017]

In anaesthetised rabbits, platelet activating factor (PAF-acether) led to decreased platelet counts and blood pressure, while CV3988 effectively inhibited these responses to PAF-acether, indicating its potential as a protective agent against PAF-induced effects.

CV3988 also inhibited the platelet count response to collagen in rabbits, but did not significantly improve survival rates, suggesting that while it can modulate platelet activity, its overall impact on survival in severe conditions may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CV3988 inhibits in vivo platelet aggregation induced by PAF-acether and collagen. Robertson, DN., Smith, GM.[2019]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Clinical biology and potential use of thrombopoietin. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Romiplostim or standard of care in patients with immune thrombocytopenia. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Opportunities for the use of thrombopoietic growth factors. [2005]

5. Germany pubmed.ncbi.nlm.nih.gov

Chronic immune thrombocytopenic purpura. New agents. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Intravenous and oral antiplatelet/antithrombotic efficacy and specificity of XR300, a novel nonpeptide platelet GPIIb/IIIa antagonist. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Inhibition of platelet aggregation by a new agent, 2,2'-dithiobis-(N-2-hydroxypropyl benzamide) (KF4939). [2019]

8. United States pubmed.ncbi.nlm.nih.gov

The in vivo pharmacological profile of the novel glycoprotein IIb/IIIa antagonist, SK&F 106760. [2003]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Ex vivo effects of SR 27417, a novel PAF antagonist, on rabbit platelet aggregation and [3H]-PAF binding. [2017]

10. Netherlands pubmed.ncbi.nlm.nih.gov

CV3988 inhibits in vivo platelet aggregation induced by PAF-acether and collagen. [2019]