trichuriasis, mansonellosis, onchocerciasis and loiasis
Conditions
Interventions
Oxfendazole 400 mg QD 1 day T. trichiura
Oxfendazole 800 mg QD 1 day T. trichiura
Placebo SD T. trichiura
Oxfendazole 400 mg QD 5 day O. volvulus L. loa M perstans
Oxfendazole 800 mg QD 5 day O. volvulus L. loa M perstans
Placebo MD 5 days
Adaptive Arm Oxfendazole 400 mg MD 5 days
Adaptive Arm Oxfendazole 800 mg QD 5 days
Adaptive Arm Oxfendazole 800 mg QD 2x 5 days
Adaptive Arm Placebo QD 2x 5 days
Oxfendazole 800 mg QD 3 days T. Trichuris
Adaptive Arm Placebo QD 5 days
Sponsors
University of Buea
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participant must be the legal age of consent in the jurisdiction in which the clinical trial is taking place to 65 years of age inclusive, at the time of signing the informed consent. A diagnosis of one or more of the following: trichuriasis, mansonellosis, onchocerciasis and loiasis confirmed within 3 months before randomization. Body weight at screening = 45 kg. Willingness of women of child-bearing potential to use a culturally acceptable, highly effective method of contraception, which is effective before the first IP intake and for at least 33 days after the last IP intake. Willingness of male participants to use a male condom for vaginal intercourse with female partners of childbearing potential in each course of study treatment : from first day of IP administration to 33 days from the last IP . Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Participant is deemed clinically suitable for a placebo-controlled study of the duration planned. O. volvulus infection: diagnosed by skin snip method: documented mf positivity on skin assessment on at least 2 out of 4 skin snips. Presence of at least 1 excisable subcutaneous nodule/ onchocercoma detected through palpation Loa loa: infection as evidenced by peripheral microfilaremia assessed between 10am-4pm between 100-8,000 mf/ml M. perstans: infection diagnosed by mf-positivity in blood = 200 mf/ml blood (10 mf via finger prick/~50µl) Trichuris trichiura: Being able and willing to provide two stool samples at screening and at follow-up assessment. Having at least two out of four Kato-Katz slides positive for T. trichiura at screening.
Exclusion criteria
Exclusion criteria: Any condition, in the investigator's opinion, that places the participant at undue risk (symptoms, physical signs, vital signs or biological/laboratory signs suggestive of past or present systemic disorders, including but not limited to, cardiovascular, pulmonary, cutaneous, immunodeficiency, hepatic, renal, hematologic, psychiatric disorders, drug / alcohol abuse and other abnormalities likely to interfere with the interpretation of results of the trial) or to significantly affect the study outcomes as judged by the investigator. Current or chronic history of liver disease. This includes any liver disease considered clinically significant by the investigator (see protocol). Pregnant and breastfeeding women Hb 1.5xULN at baseline. eGFR (using the Modification of Diet in Renal Disease equation, (Beck, 2023)) 2 weeks course) prior baseline Use of concomitant medication that is contraindicated with benzimidazoles and/or known hypersensitivity to benzimidazoles or any other ingredient in the oxfendazole tablet formulation Current or planned use of another investigational drug at any point during study participation. Participation in any interventional study within 3 months prior to screening or during the study, or within 5 times the half-life of the drug in the previous clinical trial, whichever is longer (time calculated relative to final in previous trial)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Identify a safe and efficient dose of oxfendazole for each of the four indications: participants infected with one or more of the following: Onchocerca volvulus (onchocerciasis), Loa loa (loiasis), Mansonella perstans (mansonellosis) or Trichuris trichiura (trichuriasis). The associated endpoint is parasite load at day 18 (egg count for trichuriasis) and/or month 12 (mf count for all other indications). | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate the safety, tolerability, characteristics of oxfendazole in helminth infected individuals. The associated endpoint is frequency of adverse events (AEs), serious adverse events (SAEs) and discontinuations or temporary suspensions of IP up to day 18 (and day 45 for Arms 10, 11) and to the end of the trial;To demonstrate pharmacokinetics characteristics of oxfendazole in helminth infected individuals. The associated endpoint is PK parameters (AUC0-t, AUC0-8, AUCtau, Cmax, Tmax, t1/2 and Racc) of oxfendazole.;Onchocerca volvulus infection ? Absence of live female adult worms with normal embryogenesis (assessed by histological examination of nodules collected at month 12) ? Relative reduction of skin mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Absence of skin mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Absence of signs and symptoms of onchocerciasis day 18 (and day 45 for Arms 10, 11), month 3, 6, 9 and 12;Loa loa infection ? Relative reduction of L. loa blood mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Area under the curve of L. loa blood mf during follow-up period for each dose level ? Absence of L. loa blood mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Absence of signs and symptoms due to eye worm migration and Calabar swelling day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12;Mansonella perstans infection ? Relative reduction of M. perstans blood mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Area under the curve of M. perstans blood mf during follow-up period for each dose level ? Absence of M. perstans blood mf at day 18, (and day 45 for arms 10, 11), month 3, 6, 9 and 12 ? Absence of signs and symptoms of pruritus, urticaria and oedema at day 18 (and day 45 for arms 10, 11), month 3, 6, 9 and 12;Trichuris trichiura infection ? Relative reduction of eggs (egg reduction rate) at day 18 (assessed by quadrupl | — |
Countries
Cameroon, Democratic Republic of the Congo, Gabon, United Republic of Tanzania
Contacts
Public ContactGlory ;Jennifer Amambo;Keiser
Head of Department of Microbiology and Parasitology University of Buea;Professor
Outcome results
None listed