Tafenoquine for Babesiosis

Overseen By Geoff Dow

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: 60 Degrees Pharmaceuticals LLC

Must be taking: Antimicrobials

Must not be taking: Quinine

Disqualifiers: Significant illness, Pregnancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 days

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a double-blind, randomized, multisite, placebo-controlled trial comparing the safety and efficacy of TQ versus placebo in patients hospitalized for babesiosis with low risk for relapsing disease who will also be administered a standard-of-care antimicrobial regimen (A/A) that is recommended in the 2020 IDSA guideline on the diagnosis and management of babesiosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that some medications might be excluded. It's best to discuss your current medications with the trial team to see if any are not allowed.

What data supports the effectiveness of the drug tafenoquine for treating babesiosis?

Tafenoquine has shown effectiveness in treating Babesia microti infections in animal models, and it was used to treat a patient with a resistant strain of the infection. However, there are reports of relapse in both animal models and an immunocompromised patient, suggesting that more research is needed to determine the best treatment approach. ^{1 2 3 4 5}

Is tafenoquine safe for humans?

Tafenoquine has been approved for use in humans for malaria prevention and treatment, and studies suggest it does not cause neurological issues like some similar drugs. However, more research is needed to fully understand its safety for treating babesiosis, especially in people with weakened immune systems. ^{1 2 3 4 5}

How is the drug tafenoquine unique in treating babesiosis?

Tafenoquine is unique because it is an oral drug originally developed for malaria that shows promise in treating babesiosis, especially in cases resistant to standard treatments like azithromycin and atovaquone. It works differently by potentially affecting the parasite's mitochondria and inhibiting haematin polymerization, but more research is needed to confirm its effectiveness and optimal use for babesiosis. ^{1 2 3 4 5}

Eligibility Criteria

Adults hospitalized for babesiosis who can take oral meds, have good vein access for blood draws, and agree to birth control if of reproductive age. They must not join other drug studies simultaneously, be confirmed with Babesia infection showing symptoms, and consent to study requirements.

Inclusion Criteria

Laboratory confirmed infection with Babesia

Must agree not to enroll in another study of an investigational agent prior to completion of the study

Blood hemoglobin ≥ 7 g/dL

Exclusion Criteria

I have a serious health condition not related to babesiosis.

Receipt of any experimental treatment for babesiosis

Positive pregnancy test

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 days

1 visit (in-person)

Treatment

Participants receive either tafenoquine or placebo along with standard-of-care antimicrobial regimen for 4 days

4 days

Daily visits (in-person) during hospitalization

Follow-up

Participants are monitored for sustained clinical resolution and molecular cure

90 days

Periodic follow-up visits

Treatment Details

Interventions

• Tafenoquine

Trial Overview The trial tests Tafenoquine (TQ) plus standard care against a placebo plus standard care in patients with babesiosis. It's double-blind (neither doctors nor patients know who gets what), randomized (assigned by chance), at multiple sites, and checks safety and effectiveness.

Participant Groups

Group I: Group 1 Active Control 1 Intervention

TQ: 2 x 100 mg TQ tablets orally on Days 1, 2, 3, and 4

Group II: Group 2 Placebo Group 1 Intervention

Placebo: 2 x 100 mg placebo tablets orally on Days 1, 2, 3, and 4

Tafenoquine is already approved in United States for the following indications:

Approved in United States as Arakoda for:

• Malaria
• Prevention of relapse of Plasmodium vivax malaria

Approved in United States as Krintafel for:

• Malaria
• Prevention of relapse of Plasmodium vivax malaria

Who Is Running the Clinical Trial?

60 Degrees Pharmaceuticals LLC

Lead Sponsor

Trials

6

Recruited

760+

Findings from Research

Tafenoquine was effective in eliminating visible Babesia microti parasites in mouse models, but all mice relapsed except those treated with artesunate, indicating that tafenoquine alone may not be sufficient to prevent relapse.

An immunocompromised patient experienced a relapse of infection after a 46-day tafenoquine treatment, suggesting that longer treatment durations or combination therapies may be necessary for effective management in such patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of an Approximately Six Week Course of Tafenoquine to Completely Eradicate Babesia microti Infection in an Immunocompromised Patient. Prasad, PJ., Wormser, GP.[2022]

Tafenoquine is an effective oral anti-malarial drug approved for the radical cure of P. vivax malaria and for malaria prophylaxis, demonstrating its dual action against both liver and blood stages of the parasite.

The exact mechanism of tafenoquine's action is not fully understood, but it may involve inhibiting haematin polymerization and inducing mitochondrial dysfunction in the malaria-causing organisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafenoquine: First Global Approval. Frampton, JE.[2019]

Tafenoquine has shown high effectiveness against Babesia microti infections in animal models, suggesting its potential as a treatment option.

In a case study, an immunocompromised patient with a resistant strain of B. microti was successfully treated with tafenoquine, indicating its possible efficacy in challenging cases of babesiosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tafenoquine to treat a patient with relapsing babesiosis with clinical and molecular evidence of resistance to azithromycin and atovaquone. Marcos, LA., Leung, A., Kirkman, L., et al.[2022]

Tafenoquine (TQ) demonstrated a strong efficacy in treating Babesia microti infection in SCID mice, completely eliminating detectable parasites and achieving over 90% reduction in parasitemia within 4 days after treatment.

The study found no evidence of drug resistance developing against TQ, suggesting it could be a promising treatment option for B. microti infections in humans, pending further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could the Drug Tafenoquine Revolutionize Treatment of Babesia microti Infection? Mordue, DG., Wormser, GP.[2020]

Tafenoquine, recently approved for treating Plasmodium vivax malaria, does not show the same neurotoxic effects as older 8-aminoquinoline drugs like pamaquine and plasmocid, based on a review of both non-clinical and clinical literature.

Unlike some older malaria treatments that caused specific neurological damage in Rhesus monkeys and humans, there is no evidence of similar neurotoxicity associated with tafenoquine or primaquine, suggesting they are safer options for malaria treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines. Berman, J., Brown, T., Dow, G., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Failure of an Approximately Six Week Course of Tafenoquine to Completely Eradicate Babesia microti Infection in an Immunocompromised Patient. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tafenoquine: First Global Approval. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Use of tafenoquine to treat a patient with relapsing babesiosis with clinical and molecular evidence of resistance to azithromycin and atovaquone. [2022]

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

Could the Drug Tafenoquine Revolutionize Treatment of Babesia microti Infection? [2020]

5. England pubmed.ncbi.nlm.nih.gov

Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines. [2023]