Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202303704849277 Date of Approval: 29/03/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A clinical phase IIa randomized, ascending dose, placebo-controlled, assessor-blind, safety, tolerability and efficacy study of orally administered Moxidectin in subjects with microfilaraemic Loa loa infection
Official scientific title A clinical phase IIa randomized, ascending dose, placebo-controlled, assessor-blind, safety, tolerability and efficacy study of orally administered Moxidectin in subjects with microfilaraemic Loa loa infection
Brief summary describing the background and objectives of the trial Loiasis is a highly neglected filarial disease endemic in Central and West Africa. The true disease burden of loiasis and associated increased mortality have been established only recently and indicate similar overall disability adjusted life years due to loiasis as to other leading neglected tropical diseases (NTD) such as schistosomiasis. There are currently no control programmes in endemic regions in place mostly due to a lack of drugs suitable for individual treatment or mass drug administration programmes aiming to reduce overall transmission. One drug that has demonstrated substantial reduction of microfilaraemia in loiasis patients is the macrolytic lactone Ivermectin (IVM). However, due to the short half-life the L. loa microfilarial densities (MFD) is not sufficiently suppressed to have a significant effect on the transmission of loiasis. Moxidectin (MOX), another avermectin, has a significantly longer halflife and it is thus hypothesized that MOX may lead to longer lasting suppression of L. loa MFD in peripheral blood with a consequential reduction of the onward transmission of loiasis. This project aims to establish first evidence for the safety, tolerability and pharmacodynamics of MOX when used for the treatment of loiasis in endemic regions. A three-arm randomized, placebo-controlled, double-blind, clinical trial will be conducted at the CERMEL in Gabon with placebo, IVM and an experimental treatment assignment with MOX, respectively. After a safety roll-in phase with low-dose MOX 4 mg (n=35), progression to the second cohort (n=130) for the experimental treatment dose, MOX 8 mg, will be authorized by the DSMB only if no drug related grade 3 Adverse Events (AEs) was recorded within the first month after treatment. After the single-dose treatment all subjects (n=165) will be followed-up closely for safety and assessment of MFD and thereafter up to 18 months.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Loiasis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 16/04/2023
Actual trial start date 16/04/2023
Anticipated date of last follow up 31/03/2025
Actual Last follow-up date 31/07/2025
Anticipated target sample size (number of participants) 165
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Moxidectin Moxidectin 4mg stat, oral, in the safety-roll-in phase (n=20) and Moxidectin 8mg stat, oral, in the second cohort (n=80) medication is given only once, observation over 18 months drug administered orally once at baseline (Day 0). 100
Control Group Ivermectin Ivermectin 150ug/kg stat, oral (n=50) Ivermectin is giving only once at baseline (day 0), observation over 18 months drug administered orally once at baseline (day 0) 50 Active-Treatment of Control Group
Control Group Placebo Placebo with no active ingredient will be given orally, 3 tbs Placebo is administered orally once at baseline (day 0), observation over 18 months Placebo administered once orally at baseline (day 0) 15 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Both sexes, Aged 18 to 65 years, inclusive • Body weight ≥ 40 kg • Good general condition, as determined by the medical questionnaire and clinical examination • Hematological parameters and adequate renal and hepatic functions, such as: o Leukocytes ≥ 3,000 and ≤ 11,300 cells/ml o Hemoglobin ≥ 8.0 g/dl o Platelets ≥75,000/mm3 o Serum creatinine ≤ 2.5 x ULN o Total bilirubinemia ≤ 1.5 x ULN o ALT ≤ 3.0 x ULN o AST ≤ 3.0 x ULN o Negative urinary strip: absence of leukocyturia, hematuria, and proteinuria (in case of positivity, a second urinary strip test will be made for con-firmation) • Blood microfilarial density 1-1,000/ml or 1,000-2,000/ ml according to the recruit-ment cohort, respectively • Written, signed and dated informed con-sent of participant or impartial witness • Ability to take oral treatment and willing-ness to comply with the study procedures (covered by the informed consent) • Ongoing participation in any interventional trial. • Any vaccination within 2 weeks before study drug administration • Acute infection requiring antibiotic therapy within the last 10 days before study drug administration • Concomitant administration of drugs of the benzodiazepine class (s. Annex) • Known past or current history of neurolog-ical or neuropsychiatric disease or epilepsy (incl. previous meningitis, encephalitis) • History of drug or alcohol abuse • Any condition, in the investigator's opinion, that places the subject at undue risk • Subjects who have donated blood within 8 weeks before study entry • Antifilarial therapy within the previous year (DEC, IVM, albendazole for more than 7 days) • History of severe drug-induced hypersensi-tivity reaction during previous medical treatment or mild to moderate hypersensi-tivity reaction to macrolytic lactones • Known intolerance to IVM, MOX or any of the excipients (including placebo) • Pregnant and breastfeeding women Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/12/2022 Comite d Ethique Institutionnel
Ethics Committee Address
Street address City Postal code Country
BP 242 Lamabarene 00000 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • The primary purpose of this study is to determine the safety and tolerability of single dose 8 mg moxidectin (MOX) in subjects infected with L. loa compared to ivermectin (IVM). primary endpoint: within the first 28 days post-treatment, secondary endpoint: over the entire study period
Secondary Outcome To compare the reduction of L. loa microfilarial density (MFD) after single dose MOX therapy to the reduction of MFD after single dose IVM or placebo • To compare the long-term duration of MFD reduction after single dose MOX to the any MFD reduction after single dose IVM or placebo by measuring monthly L.loa MFD over 18 months • To compare the reduction of patient-centred outcomes (clinical manifestations and eosinophil levels) over 18 months post MOX-treatment compared to IVM and placebo primary parasitological endpoint: 6 months post-treatment and at nadir, secondary parasitological endpoint: at day 3, 7, 14 and month 1, 3, 6, 12, 15 and 18 after treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicales de Lambarene BP 242 Lambarene 00000 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
German Centre for Infectious Diseases Inhoffenstr. 7 Braunschweig 38124 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Bernhard Nocht Institut for Tropical Medicine Bernhard Nocht Strasse 74 Hamburg 20359 Germany University
COLLABORATORS
Name Street address City Postal code Country
University Hospital Bonn Venusberg-Campus 1 Bonn 53127 Germany
Centre de Recherches Medicales de Lambarene BP 242 Lambarene 00000 Gabon
Institut de Recherche pour le Developpement 911 Av. Agropolis Montpellier 34394 France
Medicines Development for Global Health 1/18 Kavanagh St Southbank Melbourne 3006 Australia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ghyslain Mombo Ngoma ghyslain.mombongoma@cermel.org +24174125664 BP 242
City Postal code Country Position/Affiliation
Lambarene 00000 Gabon Head of the Clinical Operations department
Role Name Email Phone Street address
Public Enquiries Lidiwne Badjina lidwine.badjina@bnitm.de +4940285380705 Bernhard Nocht Strasse 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany Project Manager
Role Name Email Phone Street address
Scientific Enquiries Michael Ramharter ramharter@bnitm.de +494042818511 Bernhard Nocht Institut for Tropical Medicine
City Postal code Country Position/Affiliation
Hamburg Germany Head of clinical research study coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes In line with the funding conditions, IPD is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The below mentioned URL will carry information on how to access the IPD at the end of the study and addresses that contain additional information about the plan to share IPD. This will include the repository in which the IPD will be deposited. The website shall also explain the eligibility criteria and internal review processes for reviewing data requests. Clinical Study Report,Informed Consent Form,Study Protocol From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. This IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form Evaluation by a data access committee Data sharing Agreement Secure transfer of data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information