Uncomplicated MalariaPhase 1ZYFER-1NCT05911828
A Study to Determine Safety, Tolerability, and Pharmacokinetics of Different Orally Administered Regimens of the Combination ZY19489-Ferroquine in Adult Asymptomatic Plasmodium Falciparum Carriers
A Phase 1 study testing ZY19489 + Ferroquine (FQ) in people with Uncomplicated Malaria and Asymptomatic Condition, run by Zydus Lifesciences Limited at 1 site in Gabon.
Trial summary
Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Uncomplicated Malaria, Asymptomatic Condition, Falciparum Malaria
- What is being tested?
- ZY19489 + Ferroquine (FQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteGabon
- Study dates
- 30 Aug 2024to 30 May 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1. Male and female (non-pregnant, non-lactating) subjects aged between 18 and 55 years old 2. Participant's body weight ≥ 45 kg 3. Evidence of asymptomatic infection with Plasmodium falciparum mono-infection on microscopy with parasite density between 20/µL and 5000/µL.
- 4. Participants should agree to not donate blood from enrolment in the study until end of the follow-up period 5. Ability to swallow oral medication 6. Evidence of written informed consent personally signed and dated by the participant.
- Signed informed consent obtained prior to participation in the study. In case of participant unable to read and write or otherwise incapable of signing an informed consent, an impartial witnessed consent shall be obtained. Participants who are willing to and are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Who cannot join
- 1. Mixed Plasmodium infection as judged by microscopy. 2. Presence of clinically significant infectious disease or fever (e.g. Body temperature ≥38°C or 100.4°F) within the 14 days prior to enrollment.
- 3. History of alcohol or drug abuse or positive urine alcohol test or urine drug test.
- 4. Consumption of beverages or food containing xanthine bases including chocolate, coffee etc. from 48 hours prior to enrollment.
- 5. Known allergy to the study drugs and to the rescue medications (artemisinin derivatives, lumefantrine) as well as their excipients.
- 6. History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:
- Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to screening.
Show all 14Show fewer
- Amodiaquine, chloroquine within 4 weeks prior to screening.
- Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other anti-malarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to screening.
- 7. Laboratory parameters outside normal range or with clinically relevant abnormalities as per investigator's judgment.
- 8. Electrolyte levels outside normal range 9. Hematology, clinical chemistry or urinalysis results at screening that were outside of clinically acceptable laboratory ranges and were considered clinically significant by the Investigator.
- 10. GFR<60 ml/min. 11. Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance within 3 months of screening.
- 12. Participation in other clinical studies within 90 days before screening. 13. Pregnant or nursing (lactating) women. 14. Sexually active participants not willing to take effective contraception measures from enrolment until the last study visit: For female participants, combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner.
- 15. All male participants not willing to use either true abstinence, barrier method or with their sexual partner, the use of effective means of contraception from enrolment and until the last study visit.
- 16. Participant who the investigator considers at particular risk of receiving an anti-malarial or of participating in the study.
Trial locations and contacts
1 site in 1 country.
Gabon1 site, 1 recruiting
- Recruiting
Centre de Recherches Médicales de Lambaréné
Lambaréné
DEARIE GLORY OKWU
About this study
Official title: Phase Ib, Single-center, Randomized, Study to Determine Safety, Tolerability, and Pharmacokinetics of Different Orally Administered Regimens of the Combination ZY19489-Ferroquine in Adult Asymptomatic Plasmodium Falciparum Carriers
Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Plasmodium falciparum can lead to severe malaria and accounts for 90% of malaria deaths that mainly occur in children below the age of 5 years in Sub-Saharan Africa.
A simplified treatment regimen, ideally a single-day cure (or at most 2-day dosing regimen), of uncomplicated malaria due to P. falciparum would be the magic in the antimalarial armamentarium. Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also the transmission of malaria, and such a regimen would substantially increase adherence. To find a new non-artemisinin combination therapy with a shorter regimen, ideally, a single-dose cure, with low resistance potential would be the aim. The two compounds tested here are ZY19489, a triaminopyrimidine, and ferroquine (FQ), a next-generation 4-aminoquinoline. Both compounds show unique features in terms of long half-life, and activity against current drug-resistant strains.
Therefore, the main goal of this clinical trial is to assess the safety of the ZY19489-FQ combination given as a 1- or 2-day dose regimen.
Read the detailed description
Total of 36 participants (3 cohorts with up to 12 participants each).The participant will receive the intervention orally once daily for one or two days, following a fasting period of at least 10 hours.Total duration of trial participation for each participant: Approximately 10 weeks (screening visits + 64 days of follow-up).
- Being tested
- ZY19489 + Ferroquine (FQ), Placebo
- Medical subject headings
- Asymptomatic Diseases, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZY19489 + Ferroquine (FQ)Drug
ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h.
PlaceboDrug
ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h.
| Study group | Role | What they receive |
|---|---|---|
| ZY19489 + Ferroquine (FQ) | Active comparator | A single daily dose 600 mg ZY19489 + 600 mg FQ, or 900 mg ZY19489 + 900 mg FQ are selected as the doses to be evaluated in Cohort 1 and 2, respectively. A daily dose of 600 mg ZY19489 + 600 mg FQ will be administered daily for 2 days in Cohort 3.
ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. Receives: Drug: ZY19489 + Ferroquine (FQ) |
| Placebo | Placebo comparator | ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence, severity and relationship to ZY19489-FQ of treatment emergent adverse events
To evaluate the safety and tolerability of ZY19489-FQ combination in African adult asymptomatic carriers of Plasmodium falciparum mono-infections.
Measured: Day 0 to Day 64
Secondary outcomes (8)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t).
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Area under the curve from the time of dosing to the infinity (AUC0-∞)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Maximum plasma concentration (Cmax)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Time to reach maximum plasma concentration (Tmax)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Terminal half life (t1/2)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Clearance (CL/F)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Volume of distribution (Vd/F)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Elimination rate constant (λ)
Estimation of PK parameters of ZY19489, its major metabolite and FQ and its major metabolite using noncompartmental method.To characterize the PK of ZY19489-FQ combination in African asymptomatic adult carriers of Plasmodium falciparum mono-infections
Measured: Day 0 to Day 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start30 Aug 2024
- Primary completion1 Feb 2025 (estimated)
- Study completion30 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zydus Lifesciences Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Deven Parmar, MD,FCP, Study director, Zydus Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05911828
- Sponsor's protocol ID
- ZY-19489.23.001
- Acronym
- ZYFER-1
- Status last verified
- Jun 2024
- First submitted
- 4 Jun 2023
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib, Single-center, Randomized, Study to Determine Safety, Tolerability, and Pharmacokinetics of Different Orally Administered Regimens of the Combination ZY19489-Ferroquine in Adult Asymptomatic Plasmodium Falciparum Carriers
- ClinicalTrials.gov ID
- NCT05911828
- Acronym / sponsor ID
- ZYFER-1 / ZY-19489.23.001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Zydus Lifesciences LimitedIndustry (pharma, biotech, devices)
- Study start
- 30 Aug 2024 (actual)
- Primary completion
- 1 Feb 2025 (estimated)
- Study completion
- 30 May 2025 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Plasmodium falciparum can lead to severe malaria and accounts for 90% of malaria deaths that mainly occur in children below the age of 5 years in Sub-Saharan Africa.
A simplified treatment regimen, ideally a single-day cure (or at most 2-day dosing regimen), of uncomplicated malaria due to P. falciparum would be the magic in the antimalarial armamentarium. Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also the transmission of malaria, and such a regimen would substantially increase adherence. To find a new non-artemisinin combination therapy with a shorter regimen, ideally, a single-dose cure, with low resistance potential would be the aim. The two compounds tested here are ZY19489, a triaminopyrimidine, and ferroquine (FQ), a next-generation 4-aminoquinoline. Both compounds show unique features in terms of long half-life, and activity against current drug-resistant strains.
Therefore, the main goal of this clinical trial is to assess the safety of the ZY19489-FQ combination given as a 1- or 2-day dose regimen.
Detailed description
Total of 36 participants (3 cohorts with up to 12 participants each).The participant will receive the intervention orally once daily for one or two days, following a fasting period of at least 10 hours.Total duration of trial participation for each participant: Approximately 10 weeks (screening visits + 64 days of follow-up).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZY19489 + Ferroquine (FQ) | Active comparator | Drug: ZY19489 + Ferroquine (FQ)A single daily dose 600 mg ZY19489 + 600 mg FQ, or 900 mg ZY19489 + 900 mg FQ are selected as the doses to be evaluated in Cohort 1 and 2, respectively. A daily dose of 600 mg ZY19489 + 600 mg FQ will be administered daily for 2 days in Cohort 3. ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. |
| Placebo | Placebo comparator | Drug: PlaceboZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 1. Male and female (non-pregnant, non-lactating) subjects aged between 18 and 55 years old 2. Participant's body weight ≥ 45 kg 3. Evidence of asymptomatic infection with Plasmodium falciparum mono-infection on microscopy with parasite density between 20/µL and 5000/µL.
- 4. Participants should agree to not donate blood from enrolment in the study until end of the follow-up period 5. Ability to swallow oral medication 6. Evidence of written informed consent personally signed and dated by the participant.
- Signed informed consent obtained prior to participation in the study. In case of participant unable to read and write or otherwise incapable of signing an informed consent, an impartial witnessed consent shall be obtained. Participants who are willing to and are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Key exclusion criteria (14 listed)
- 1. Mixed Plasmodium infection as judged by microscopy. 2. Presence of clinically significant infectious disease or fever (e.g. Body temperature ≥38°C or 100.4°F) within the 14 days prior to enrollment.
- 3. History of alcohol or drug abuse or positive urine alcohol test or urine drug test.
- 4. Consumption of beverages or food containing xanthine bases including chocolate, coffee etc. from 48 hours prior to enrollment.
- 5. Known allergy to the study drugs and to the rescue medications (artemisinin derivatives, lumefantrine) as well as their excipients.
- 6. History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZY19489 + Ferroquine (FQ)ZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. | Drug | ZY19489 + Ferroquine (FQ) |
| PlaceboZY19489-FQ combination or placebo orally after a fasting period of at least 10 h. | Drug | Placebo |
Primary outcome
incidence, severity and relationship to ZY19489-FQ of treatment emergent adverse events
Time frame: Day 0 to Day 64
To evaluate the safety and tolerability of ZY19489-FQ combination in African adult asymptomatic carriers of Plasmodium falciparum mono-infections.
8 secondary outcomes
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t).
Time frame: Day 0 to Day 64
Area under the curve from the time of dosing to the infinity (AUC0-∞)
Time frame: Day 0 to Day 64
Maximum plasma concentration (Cmax)
Time frame: Day 0 to Day 64
Time to reach maximum plasma concentration (Tmax)
Time frame: Day 0 to Day 64
Terminal half life (t1/2)
Time frame: Day 0 to Day 64
Clearance (CL/F)
Time frame: Day 0 to Day 64
Volume of distribution (Vd/F)
Time frame: Day 0 to Day 64
Elimination rate constant (λ)
Time frame: Day 0 to Day 64
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Individual participant dataSharing planned: No
Related trials for Uncomplicated Malaria
RecruitingPhase 2
Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria (Cohort C2)
Uncomplicated Plasmodium Falciparum Malaria
Not yet recruitingObservational study
Ethiopian Antimalarial Therapeutic Efficacy Study 2026
Plasmodium Vivax Malaria Without Complication, Plasmodium Falciparum Malaria (Uncomplicated)
Not yet recruiting
Tafenoquine Combinations for Improved Radical Cure Efficacy of Plasmodium Vivax
Uncomplicated P. Vivax Mono-infection
Not yet recruitingPhase 4
Investigating the Pharmacology of Tafenoquine in Papua New Guinean Children With Uncomplicated Malaria
Uncomplicated Malaria
Active, not recruitingPhase 2/3
Pharmacokinetics and Pharmacodynamics of the Gametocytocidal and Post-treatment Chemoprotective Effects of Antimalarials
Uncomplicated Falciparum Malaria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Deven Parmar, MD,FCP study director
Zydus Therapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZY19489 + Ferroquine (FQ) in people with Uncomplicated Malaria and Asymptomatic Condition, run by Zydus Lifesciences Limited at 1 site in Gabon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Gabon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kevinkumar Kansagra, MD (02717-665555 ext. 451, kevinkumarkansagra@zyduslife.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence, severity and relationship to ZY19489-FQ of treatment emergent adverse events (time frame: Day 0 to Day 64). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024; AzTrials last refreshed its copy on 7 Nov 2026.