IVM Alone vs ALB + IVM Against Onchocerciasis

NCT03238131 | Completed Phase 3

• 1 other identifier: 11-11-36
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

Brief Summary

Onchocerciasis is a vector-borne nematode parasitic disease that causes severe disability. Onchocerciasis affects approximately 33 million people, mostly in 30 countries in sub-Saharan Africa (with small foci in Latin America and Yemen) 1This disease causes blindness and severe skin disease and it is spread by black flies. O. volvulus adult worms live in subcutaneous nodules. O. volvulus adult worms are larger and less sensitive to available drug treatments than those of the species that cause Lymphatic Filariasis (LF). They also have a longer lifespan (approximately 14 years rather than the estimated 7 years for LF parasites). Several programs and developments have greatly improved the Onchocerciasis. situation since the 1970's when the Onchocerciasis Control Programme (OCP) in West Africa (green countries in the map) was initiated. OCP relied exclusively on vector (black fly) control in its early years. However, following the appearance of Ivermectin (Mectizan) on the scene in the late 1980's, OCP transitioned to become a drug distribution program with annual IVM MDA in 11 countries. OCP ended in 2002. This was replaced by the African Program for Onchocerciasis Control (APOC) which coordinates community directed distribution of IVM MDA in 28 African countries (including the former OCP countries). OCP and APOC have done a good job of reducing parasite infection intensities and Onchocerciasis disease rates in many endemic countries. Unfortunately, there is no real end in sight for the APOC approach (apart from a funding endpoint in 2015); while it may be possible to eliminate Onchocerciasis. In selected areas by MDA with IVM (alone, or combined with vector control), disease control programs in most African countries will require active maintenance for many years to come. While IVR has good activity against the parasite larvae that cause disease in the skin and eye (microfilariae or Mf), it does not kill O. volvulus adult worms, and they resume production of Mf that can lead to transmission of new Onchocerciasis. Cases by black flies after a few months. APOC activities are focused on areas with high infection rates (where disease risks are highest). However, extensive areas in Africa where fewer than 20% of adult men have Onchocerciasis nodules detectable by palpation are not receiving interventions for Onchocerciasis at this time. These areas are not disease free. (Onchocerciasis dermatitis can be severe in hypoendemic areas), and they also may serve as a source for reintroduction of the parasite into previously controlled areas after interventions stop.

Conditions

Onchocerciasis

Outcome Measures

Primary Outcomes (1)

• The percent fertile female O.volvulus worms in nodules

  Total number of live versus dead female worms in nodules

  36 months

Secondary Outcomes (6)

• Percent reduction in skin Mf/mg

  0 months

• Percent reduction in skin Mf/mg

  6 months

• Percent reduction in skin Mf/mg

  18 months

• Percent reduction in skin Mf/mg

  36 months

• Number of nodules with intact Mf

  36 months

Study Arms (4)

IVM annually (standard treatment)

ACTIVE COMPARATOR

The comparator (standard treatment) IVM 200 µg/kg body weight given at 0, 12 and 24 months plus vitamin pills at 6 and 18 months.

Drug: Ivermectin

IVM plus ALB twice annually

EXPERIMENTAL

IVM 200 µg/kg plus ALB 800 mg (regardless of weight) given at 0, 6, 12, 18, 24 months

Drug: Ivermectin; Drug: Albendazole

IVM plus ALB once annually

ACTIVE COMPARATOR

IVM 200 µg/kg plus ALB 800 mg given at 0, 12, 24 months plus vitamin pills at 6 and 18 months.

Drug: Ivermectin; Drug: Albendazole

IVM twice annually

ACTIVE COMPARATOR

IVM 200 µg/kg given 0, 6, 12, 18, and 24 months

Drug: Ivermectin

Interventions

Ivermectin DRUG

Participants are either given Ivermectin alone or Ivermectin in combination with Albendazole

IVM annually (standard treatment); IVM plus ALB once annually; IVM plus ALB twice annually; IVM twice annually

Albendazole DRUG

Albendazole will be given to participants in Arm 2 and 3 in combination with Ivermectin at varying time points.

IVM plus ALB once annually; IVM plus ALB twice annually

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women 18-60 years residing in Ashanti and Central Region of Ghana
• ≥1 accessible nodules
• any Mf/mg based on skin snips
• Willingness to give informed consent to participation in the study

You may not qualify if:

• Last IVM treatment \< 7 months
• Pregnant (do pregnancy test) + breastfeeding
• Permanent disability, serious medical illnesses such as a stroke, advanced heart disease, uncontrolled diabetes, emphysema, etc that prevents or impedes study participation and/or comprehension
• Weight of \<40kg suggesting malnourishment
• AST/ALT, γ-GT \> 1.5 upper limit of normal
• Significant glycosuria or proteinuria (2+ or 3+ protein or glucose)
• Any one or more of the previous criteria is sufficient to exclude study participation
• Not willing or able to give informed consent to participate in the study.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Committee on Human Research Publications and Ethics

Kumasi, Ashanti Region, Ghana

Location

Related Publications (13)

• Basanez MG, Pion SD, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat? PLoS Med. 2006 Sep;3(9):e371. doi: 10.1371/journal.pmed.0030371.

  PMID: 17002504 BACKGROUND

• Gardon J, Boussinesq M, Kamgno J, Gardon-Wendel N, Demanga-Ngangue, Duke BO. Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet. 2002 Jul 20;360(9328):203-10. doi: 10.1016/S0140-6736(02)09456-4.

  PMID: 12133654 BACKGROUND

• Zahner H, Schares G. Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi. Acta Trop. 1993 Jan;52(4):221-66. doi: 10.1016/0001-706x(93)90010-9.

  PMID: 8094587 BACKGROUND

• Awadzi K, Hero M, Opoku O, Buttner DW, Gilles HM. The chemotherapy of onchocerciasis. XV. Studies with albendazole. Trop Med Parasitol. 1991 Dec;42(4):356-60.

  PMID: 1796233 BACKGROUND

• Awadzi K, Addy ET, Opoku NO, Plenge-Bonig A, Buttner DW. The chemotherapy of onchocerciasis XX: ivermectin in combination with albendazole. Trop Med Parasitol. 1995 Dec;46(4):213-20.

  PMID: 8826100 BACKGROUND

• Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. doi: 10.1179/000349803235001697.

  PMID: 12803872 BACKGROUND

• Horton J, Witt C, Ottesen EA, Lazdins JK, Addiss DG, Awadzi K, Beach MJ, Belizario VY, Dunyo SK, Espinel M, Gyapong JO, Hossain M, Ismail MM, Jayakody RL, Lammie PJ, Makunde W, Richard-Lenoble D, Selve B, Shenoy RK, Simonsen PE, Wamae CN, Weerasooriya MV. An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis. Parasitology. 2000;121 Suppl:S147-60. doi: 10.1017/s0031182000007423.

  PMID: 11386686 BACKGROUND

• Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. doi: 10.1097/00001432-200212000-00008.

  PMID: 12821837 BACKGROUND

• Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. doi: 10.1016/j.pt.2005.08.014. Epub 2005 Aug 26.

  PMID: 16126457 BACKGROUND

• Moreno Y, Nabhan JF, Solomon J, Mackenzie CD, Geary TG. Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20120-5. doi: 10.1073/pnas.1011983107. Epub 2010 Nov 1.

  PMID: 21041637 BACKGROUND

• Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.

  PMID: 15324466 BACKGROUND

• Kitzman D, Wei SY, Fleckenstein L. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal. 2006 Mar 3;40(4):1013-20. doi: 10.1016/j.jpba.2005.08.026. Epub 2005 Oct 19.

  PMID: 16242280 BACKGROUND

• Cringoli G, Rinaldi L, Maurelli MP, Utzinger J. FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc. 2010 Mar;5(3):503-15. doi: 10.1038/nprot.2009.235. Epub 2010 Feb 25.

  PMID: 20203667 BACKGROUND

MeSH Terms

Conditions

Onchocerciasis

Interventions

Ivermectin; Albendazole

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of International Health, Medicine and Pathology

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: August 3, 2017
• Study Start: April 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: October 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

GH (1)