MOXIDECTIN FOR ONCHOCERCIASIS ELIMINATION...Onchocerciasis Research Network Meeting, 11Kampala, 3 -4 October 2018 Moxidectin 8 mg (n=8,000) Adults and adolescents > 12 years • Reside

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)

2Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

WHO/APOC/TDR/Kuesel

3Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

On the road from Monrovia to Lofa County, Liberia (J. Kealy)

4Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

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

6Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

Dr. Awadzi

Dr. Ukety Dr. Kanza

Dr. BakajikaDr. Howard

Dr. Opoku

7Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

PHASE 3 EFFICACY DATA FOR US FDA APPROVED DOSE OF 8MG

8Onchocerciasis Research Network Meeting, Kampala, 3-4 October 2018

PHASE 3 SAFETY DATA

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)

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

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

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

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