MOXIDECTIN FOR ONCHOCERCIASIS ELIMINATION...Onchocerciasis Research Network Meeting, 11Kampala, 3 -4...
Transcript of MOXIDECTIN FOR ONCHOCERCIASIS ELIMINATION...Onchocerciasis Research Network Meeting, 11Kampala, 3 -4...
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1Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
MOXIDECTIN FOR ONCHOCERCIASIS ELIMINATION
Studies completed
Studies in preparation
• Michel Mandro, Tony Ukety (investigators studies in DRC),
• Nicholas Opoku (investigator study in Ghana)
• C. Chesnais, J. Kamgno, M. Boussinesq (investigator study in Cameroon)
• Mark Sullivan (Founder and Managing Director, Medicines Development for Global Health),
• Annette C. Kuesel (TDR)
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2Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
WHO/APOC/TDR/Kuesel
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3Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
On the road from Monrovia to Lofa County, Liberia (J. Kealy)
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4Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
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5Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
6 Phase 1 pharmacokinetic and safety studies in healthy volunteers
• First in Human dose ranging study with liquid formulation
• Relative bioavailability of liquid and tablet formulation developed for onchocontrol programme use
• Milk-excretion study
• Drug interaction study
• Food effect study
• Cardiovascular safety study
2 comparative SINGLE DOSE safety and efficacy studies in O. volvulus infected volunteers
• Phase 2 study (Ghana, dose ranging)
• Phase 3 study (Ghana, DRC, Liberia, 8 mg)
CLINICAL STUDIES TO US FDA REGULATORY APPROVAL JUNE 2018
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6Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
Dr. Awadzi
Dr. Ukety Dr. Kanza
Dr. BakajikaDr. Howard
Dr. Opoku
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7Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
PHASE 3 EFFICACY DATA FOR US FDA APPROVED DOSE OF 8MG
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8Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
PHASE 3 SAFETY DATA
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9Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
STUDIES FOR ONCHOCERCIASIS IN PREPARATION
Multi-dose comparative efficacy study (DRC)
Single dose comparative safety study (DRC)
Pharmacokinetic and safety study in < 12 year olds (Ghana)
Single dose comparative safety and efficacy study in Loa loa infected individuals (Cameroon)
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10Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
Ivermectin 150µg/kg Annual (n=125)
Moxidectin 8mg Biannual (n=375)
Moxidectin 8mg Annual (n=375)
Ivermectin 150µg/kg Biannual (n=125)
• Adults and adolescents > 12 years
• O. volvulusinfected (mf +ve by 2 skin snips)
• N=1000
Follow up
Follow up
Follow up
Follow up
MULTI-DOSE COMPARATIVE EFFICACY STUDY (ITURI)
R
0 6 12 18 24 30 36 months
Adverse events Active (in-village assessments) to 6 days after Treatment, thereafter passive
Rx Rx Rx
Rx Rx Rx
Rx Rx Rx
Rx Rx RxRx Rx
Rx Rx
mf mf mf mf mf mf mfMF
Efficacy
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11Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
Moxidectin 8 mg (n=8,000)• Adults and adolescents > 12 years
• Reside in O. volvulusendemic area
• N=10,000
SINGLE DOSE COMPARATIVE SAFETY STUDY
R
0 1 2 3 4 5 6
Rx
Rx
Ivermectin 150 µg/kg (n=2,000)
Adverse events Active (in-village assessments) to 6 days after Treatment, thereafter passive
mf
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12Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
Moxidectin8mg (n=9)
Adolescents and Children with/at risk of O. Volvulus
(from meso- or hyperendemic Volta region of Ghana)
Exposure will be assessed but not required for study eligibility
N=9/per cohort
PK-SAFETY STUDY TO IDENTIFY SAFE DOSE IN 4-11 YEAR OLDS
0 4
Pharmacokinetic sampling: Hour 0, 1, 2, 4, 8, 24; day 3, 7, 14 and 28; Week 12Safety: Adverse Events, physical examination, changes in vital signs, laboratory valuesDose Selection for Cohort 3: safety profile, pharmacokinetic data, pharmacokinetic modelling
Rx
8 12 m
Cohort I12 to 17 yrs
Cohort 28 to 11 yrs
Cohort 34 to 7 years
Moxidectin8mg (n=9)
Rx
DSMB MoxidectinXmg (n=9)
0 4
Rx
8 12 m
PK
PK
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13Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018
Loa loa infected Adults
ASCENDING INTENSITY OF INFECTION EFFICACY-SAFETY STUDY IN LOA LOA INFECTED INDIVIDUALS
Efficacy: TBS preTx, D1, D7, D15, D90, D180, D365Safety: Active FU in village D1-D7, adverse events, laboratory values (CBC, proteinurea, leukocyturia, liver function)
Cohort ILoa loa mf/ml 1-99n=160
Moxi 2 mg
IVM 150 µg/kg
Cohort IILoa loa mf/ml 100-499n=160
Moxi 2 mg
IVM 150 µg/kgR
R
No Grade 3 AE requiring hospitalization to D7 or DSMC recommendation
Cohort IIILoa loa mf/ml 500-1000n=160
Moxi 2 mg
IVM 150 µg/kgR
No Grade 3 AE requiring hospitalization to D7 or DSMC recommendation
D0--------------------------------------------------------------M12