Safety and Efficacy of Maytenus Senegalensis for the Treatment of Uncomplicated Malaria

NCT04944966 | Completed Phase 2 DMC

• 1 other identifier: MALHERBAL
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Antimalarial Herbal medicine known as Maytenus senegalensis will be evaluated for its safety, tolerability and efficacy among Tanzanian male adults aged 18 to 45 years. The first primary objective is to assess the safety and tolerability of malaria herbal remedy of Maytenus senegalensis among healthy male adults aged 18 to 45 years in Tanzania. And the second objective is to evaluate the safety, tolerability as well as efficacy of malaria herbal remedy Maytenus senegalensis (MALHERBAL) for the treatment of Tanzanian adults aged 18 to 45 years with uncomplicated malaria compared to Artemether-lumefantrine.

Conditions

Malaria

Outcome Measures

Primary Outcomes (8)

• Number of participants with clinical significance abnormal values in hematology parameters during the follow up period of 28 days for all participants of group 1 and 2.

  Blood samples will be collected for the analysis of hematology parameters including Red cell blood count (RBC), hemoglobin (HBG), platelets (PLT), white blood cell count (WBC) with differential (neutrophil (NEUT), lymphocyte (LYMPH), and eosinophil (EO)) counts. Blood sample will be collected at Day 0(Baseline), Day 3, day 7, Day 14 and Day 28 Clinical significance abnormal values hematology parameter will be determined by adapted FDA Toxicity Grading Scale.

  up period of 28 days

• Number of participants with clinical significance abnormal values in biochemistry parameters during the follow up period of 28 days for all participants of group 1 and 2.

  Blood samples will be collected for the analysis of biochemistry parameters including ASAT, bilirubin total and creatinine. Blood sample will be collected at Day 0(Baseline), Day 3, day 7, Day 14 and Day 28. Clinical significance abnormal values of Biochemistry parameters will be determined by adapted FDA Toxicity Grading Scale.

  up period of 28

• Number of participants with significant changes in vital signs comparing to baseline during the follow up period of 28 days for all participants of group 1 and 2.

  Vital signs assessment included heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Assessments were completed at Day 0 (Baseline), Day 1 up to Day 7, Day 14, and Day 28. We be reviewed using locally prepared normal range for vital sign

  up period of 28

• Number of AEs during the follow up period of 28 days for all participants of group 1 and 2

  An Adverse Event is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The analysis was performed on all participants who received at least one dose of study treatment.

  up period of 28

• Number of SAEs during the follow up period of 56 days for all participants of group 1 and 2

  SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, other situations and is associated with liver injury or impaired liver function. The analysis was performed on all participants who received at least one dose of study treatment.

  Up period of 56

• Number of participants of group 2 with Early Treatment Failure (ETF),

  Development of danger signs or severe malaria on Day 1, Day 2 or Day 3 in the presence of parasitaemia, parasitaemia on Day 2 higher than on Day 0, irrespective of axillary temperature, parasitaemia on Day 3 with axillary temperature ≥ 37.5 ºC and parasitaemia on Day 3 ≥ 25% of count on day 0.

  Day 1 up to 3

• Number of participants of group 2 with Late Treatment Failure (LTF)

  Development of danger signs or severe malaria on any day from day 4 to day 28 in the presence of parasitaemia; without previously meeting any of the criteria of Early Treatment Failure; Presence of parasitemia + axillary temperature ≥37.5°C on any day from Day 4 to Day 28, without previously meeting any criteria of ETF.

  Day 4 up to 28

• Number of participants of group 2 with Late parasitology failure (LPF)

  Presence of parasitemia on any day from D7 to D28 + axillary temperature \<37.5°C, without previously meeting any of the criteria of ETF

  Day 7-28

Secondary Outcomes (1)

• Number of participants of group 2 with Adequate Clinical and Parasitological Response (ACPR)

  28 days

Other Outcomes (3)

• Number of developed early ring stage P. falciparum parasites

  Day 0,3,14 and 28

• Percentage of inhibitory concentration (IC50 and IC90) values of the Artemether-lumefantrine

  Day 0,3,14 and 28

• Percentage of identified resistance molecular marker of Artemether-lumefantrine

  Day 0,3,7,14,28 and 56

Study Arms (3)

Group 1

EXPERIMENTAL

• Experimental: Group 1a: n=3, Healthy male participants will receive Maytenus senegalensis administered orally at an estimated dose of 400mg once a day to test its safety and tolerability. Interventions: o Drugs: Maytenus senegalensis • Experimental: Group 1b: n=3, Healthy male participants will receive Maytenus senegalensis administered orally at an estimated dose of 600mg once a day to test its safety and tolerability. Interventions: o Drugs: Maytenus senegalensis • Experimental: Group 1c: n=3, Healthy male participants will receive Maytenus senegalensis administered orally at an estimated dose of 800mg for 8 hourly for 4 days to test its safety and tolerability. Interventions: o Drugs: Maytenus senegalensis • Experimental: Group 1d: n=3, Healthy male participants will receive Maytenus senegalensis administered orally at an estimated dose of 800mg for 8 hourly for 4 days to test its safety and tolerability. Interventions: o Drugs: Maytenus senegalensis

Drug: Maytenus Senegalensis

Group 2a

EXPERIMENTAL

Group 2a: n=52, Adults aged 18 to 45 years diagnosed with natural acquired uncomplicated malaria will be treated with Maytenus senegalensis. Patients will be treated with Maytenus senegalensis administered orally at an estimated dose of 800mg for 8 hourly for 4 days. Curative efficacy will be assessed by measure the portion of patients with Early Treatment Failure (ETF), Asexual parasite clearance time (PCT) and adequate Clinical and Parasitological Response (ACPR) for treatment at 28 days and 56 days after PCR correction of reinfection (ACPR 28 and 56 after PCR correction of reinfection Interventions: o Drugs: Maytenus senegalensis

Drug: Maytenus Senegalensis

Group 2b

ACTIVE COMPARATOR

Group 2a: n=52, Adults aged 18 to 45 years diagnosed with natural acquired uncomplicated malaria will be treated with Artemether-lumefantrine Patients will be treated with Artemether 20mg/lumefantrine 120mg administered orally by a six-dose regimen over 3 days. Curative efficacy will be assessed by measure the portion of patients with Early Treatment Failure (ETF), Asexual parasite clearance time (PCT) and adequate Clinical and Parasitological Response (ACPR) for treatment at 28 days and 56 days after PCR correction of reinfection (ACPR 28 and 56 after PCR correction of reinfection Interventions: o Drugs: Artemether 20mg/lumefantrine 120mg

Drug: Maytenus Senegalensis

Interventions

Maytenus Senegalensis DRUG

* Maytenus senegalensis (Malherbal) has a very long history of safe medicinal use in Africa in adult as well as infants and children. It will be administered orally at a dose of 800mg 8 hourly for 4 days. * Artemether 20mg/lumefantrine 120mg

Also known as: Artemether-lumefantrine

Group 1; Group 2a; Group 2b

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males based on clinical and laboratory findings
• Aged from 18 to 45 years
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2.
• Long-term (at least one year) or permanent residence in the Bagamoyo district or nearby districts.
• Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study.
• Willingness to be attended to by a study clinician and take all necessary medications prescribed during the study period
• Agreement to provide contact information of a third-party household member or close friend to study team
• Availability through mobile phone 24 hours during the entire study period
• Agreement not to participate in another clinical trial during the study period
• Agreement not to donate blood during the study period
• Able and willing to complete the study visit schedule over the study follow up period, including the hospitalizations required for protocol compliance
• Willingness to undergo HIV, hepatitis B (HBV) and hepatitis C (HCV) tests
• Able to demonstrate their understanding of the study by responding correctly to 10 out of 10 true/false statements (in a maximum of two attempts for those who failed to respond correctly to all true/false statements in the first attempt)
• Signed written informed consent, in accordance with local practice
• Free from malaria parasitaemia by blood smear at enrolment

You may not qualify if:

• Previous receipt of an investigational malaria drug in the last 5 years
• Participation in any other clinical study involving investigational medicinal products within 30 days prior to the onset of the study or during the study period
• History of arrhythmias or prolonged QT-interval or another cardiac disease, or clinically significant abnormalities in electrocardiogram (ECG) at screening
• Positive family history in a 1st or 2nd-degree relative for the cardiac disease at age \<50 years old
• A history of psychiatric disease
• Suffering from any chronic illness including; diabetes mellitus, cancer or HIV/AIDS
• Any confirmed or suspected immunosuppressive or immune-deficient condition, including asplenia
• History of drug or alcohol abuse interfering with normal social function
• The use of chronic immunosuppressive drugs or other immune-modifying drugs within three months of study onset except inhaled and topical corticosteroids.
• Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
• Positive HIV, hepatitis B virus or hepatitis C virus tests
• Suspected of having clinically active TB by history or physical examination with positive QuantiFERON-TB Gold Test In-Tube assay
• Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, blood, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers.
• Any medical, social condition, or occupational reason that, in the judgment of the study clinician, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
• Group 2

Sponsors & Collaborators

• Ifakara Health Institute: lead
• Swiss Tropical & Public Health Institute: collaborator
• Muhimbili University of Health and Allied Sciences: collaborator
• National Institute for Medical Research, Tanzania: collaborator

Study Sites (1)

Bagamoyo Clinical Trial Facility

Bagamoyo, Tanzania

Location

Related Publications (1)

• Kassimu KR, Ali AM, Omolo JJ, Mdemu A, Machumi F, Ngasala B. The effect of an anti-malarial herbal remedy, Maytenus senegalensis, on electrocardiograms of healthy Tanzanian volunteers. Malar J. 2024 Apr 12;23(1):103. doi: 10.1186/s12936-024-04935-w.

  PMID: 38609987 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Kamaka Kassim, BscN,MPH

  Ifakara Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2021
• First Posted: June 30, 2021
• Study Start: June 2, 2021
• Primary Completion: September 25, 2022
• Study Completion: September 25, 2022
• Last Updated: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)