Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03199755 |
| Other study ID # |
16-297 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
August 20, 2018 |
| Est. completion date |
October 1, 2019 |
Study information
| Verified date |
October 2021 |
| Source |
Worcester Polytechnic Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The overall goal is to validate efficacy and potential superiority of dried leaf Artemisia
annua (DLA) vs. artemisinin combination therapy (ACT) to cure malaria and to demonstrate
elimination of the transmission stage (gametocytes) of the disease. This is a 3 arm trial in
Democratic Republic of Congo covering 600 total adult and pediatric patients. Final
validation of infection from dried blood samples will be done at WPI.
Description:
A clinical trial in DR Congo to validate that oral consumption of dried leaf tablets of the
plant Artemisia annua can cure malaria and prevent its transmission.
PI: Pamela Weathers, Ph.D. & Prof. of Biology and Biotechnology, Lead Institution: Worcester
Polytechnic Institute, 100 Institute Rd, Worcester, MA 01609
Background:
The plant Artemisia annua produces artemisinin, which is currently extracted and purified
from the plant and used to produce the current standard of antimalarial care, artemisinin
combination therapy (ACT). While some human trials have been done using dried leaf Artemisia
(DLA) to treat malaria, none has been extensive enough to provide evidence convincing to the
key regulatory bodies, e.g. WHO. There is animal and human evidence suggesting that DLA not
only is highly efficacious at low doses, but also treats ACT-resistant malaria and may
inhibit development of the gametocytes, which is the blood parasite stage that enables
retransmission to the next mosquito host. ACTs have not shown full efficacy in quelling
transmission. Furthermore, ACT drug resistance is now confirmed in Southeast Asia and may be
emerging in Africa. Thus, this study is unique, timely and needed because:
- DLA has not been studied yet in a larger human trial.
- DLA has not been compared in a human trial to the current ACT antimalarial therapy.
- DLA shows promise at inhibiting the gametocyte transmission stage of malaria and would
thereby break the cycle of malaria.
- Investigators have a full supply chain in place to grow, produce and package DLA tablets
in a GMP facility and have distribution channels ready to deliver the drug to pharmacies
in Eastern Africa.
- Investigators' therapeutic approach is less costly than ACT and is under the control of
Africans; therapeutics by and for Africans.
Specific Aims:
Investigators overall goal is to validate efficacy and potential superiority of DLA vs. ACT
to cure malaria and to demonstrate elimination of the transmission stage of the disease
(gametocytes). The trial has 3 specific aims:
1. Compare overall clinical outcomes efficacy of two different doses of DLA vs. standard
ACT treatment.
2. Compare parasite level via Rapid Diagnostic Test (RDT) at D0 and then via microscopy at
D0-D5, D14, D28 on all patients from each arm of the trial (DLA1x, DLA2x vs. ACT).
3. Compare level of gametocytes via qPCR of dried blood spots at D0, D14, D28 on a randomly
selected subset of patients from each arm of trial (DLA1x, DLA2x vs. ACT).
Dried leaves of A. annua will be provided by Botanical Extracts EPZ (BEEPZ), which is a
processing facility based in the Export Processing Zone (EPZ) in Athi River, Kenya. BEEPZ
extracts and purifies raw material from an agricultural supply chain of A. annua grown in
Kenya, Uganda, and Tanzania. The pulverized dried leaves will then be exported to Rene
Industries LTD, in Kampala, Uganda. Rene is a GMP pharmaceutical facility that investigators
have inspected and that will manufacture and blister pack A. annua tablets for export to DR
Congo where patients at the Rwanguba Reference Hospital (North Kivu area) will be treated.
Patients in the Coartem Arm will receive the control ACT drug using the prescribed dosing
regimen according to RD Congo National Protocol and by the manufacturer (TABLE 1). A single
Coartem tablet contains 20 mg artemether and 120 mg lumefantrine. All ACTs will be purchased
from an EU source to obviate any counterfeit ACT drugs, which can be problematic throughout
Africa. Coartem is orally administered twice daily, morning and evening, for 3 days per WHO
and manufacturer guidelines.
Patients in the two DLA Arms will receive the drug using the following dosing scheme (TABLE
2) based on prior successful treatment of both adults and pediatric patients with the 1x
dose. A single tablet contains 500 mg A. annua DLA. Artemisinin delivered via DLA is > 40
fold more bioavailable than artemisinin delivered as pure drug, i.e. Coartem. Two doses of
DLA/day are orally delivered, morning and evening, to each patient for 5 days.
TABLE 1. Coartem dosing. Coartem tablets/dose by bodyweight; tablets/day morning and evening
for total of 6 doses over 3 days
Body weight (kg) and Tablets: 5 to <15 kg, 1 tab; 15 to <25 kg, 2 tabs; 25 to <35 kg, 3 tabs;
35 kg and over, 4 tabs.
TABLE 2. DLA dosing. DLA tablets/dose by bodyweight; tablets/day, morning and evening, for
total of 10 doses over 5 days.
Body weight (kg) and tablets/dose:
For DLA1x: 5 to < 15 kg, 1/4 tab; 15-30 kg, 1/2 tab; 1/2>30 kg, 1 tab. For DLA2x: 5 to < 15
kg, 1/2 tab; 15-30 kg, 1 tab; >30 kg, 2 tabs.
Duration:
The 600 human subjects will be recruited over 2-3 months in DRC where participants will be
treated. Dried blood samples collected over the duration of the study will be sent to WPI
where the Weathers lab will extract parasite RNA and analyze via qPCR for gametocytes. The
entire trial and PCR analyses are anticipated to take no more than 18 months.
Plesion International a Pennsylvania NGO has long term contacts with Prof. Weathers at WPI,
the DRC hospital, DRC doctors, the Ugandan GMP manufacturing facility, and now also with
BEEPZ. Plesion will manage all aspects of the African interactions and subcontract to WPI who
will manage the overall project under Prof. Weathers direction.
