The efficacy of rifapentine plus moxifloxacin against onchocerciasis: a randomized, open label pilot trial.

• Register: ISRCTN
• Last refreshed on: 14 January 2019
• Main ID: ISRCTN43697583
• Date of registration: 17/04/2015
• Prospective Registration: Yes
• Primary sponsor: Kumasi Centre for Collaborative Research (KCCR)
• Public title: The efficacy of rifapentine plus moxifloxacin against onchocerciasis: a randomized, open label pilot trial.
• Scientific title: Scientific title as of 05/12/2018: The efficacy of Rifapentine 900mg/d plus Moxifloxacin 400mg/d given for 14 or 7 days against Onchocerciasis: a randomized, parallel-group, open-label, phase II pilot trial. Previous scientific title: The efficacy of Rifapentine 600mg/d plus Moxifloxacin 400mg/d given for 14 or 7 days against Onchocerciasis: a randomized, parallel-group, open-label, phase II pilot trial.
• Date of first enrolment: 01/10/2018
• Target sample size: 80
• Recruitment status: Recruiting
• URL: http://isrctn.com/ISRCTN43697583
• Study type: Interventional
• Study design: Single-centre, interventional, randomized, parallel-group, open-label, phase II pilot trial (Treatment)
• Phase: Phase II

Countries of recruitment

Ghana

Contacts

• Name: Alexander Yaw Debrah

• Name: Ute Klarmann-Schulz

Key inclusion & exclusion criteria

Inclusion criteria:
Participant inclusion criteria as of 05/12/2018:
1. Willingness to participate in the study by signing the Informed Consent Form (ICF)
2. 18-55 years
3. Body weight > 45kg
4. Presence of at least 1 medium-sized onchocercoma detected by palpation
5. Mf-positive
6. Good general health without any clinical condition requiring medication
7. No previous history of tuberculosis
8. Participants with the ability to follow study instructions and are likely to attend and complete all required visits

Previous participant inclusion criteria:
1. Men and Women
2. 18-55 years
3. Body weight > 45kg
4. Presence of at least 3 onchocercomata detected by palpation
5. Mf-positive
6. Good general health without any clinical condition requiring long-term medication
7. No previous history of tuberculosis
8. Participants with the ability to follow study instructions and are likely to attend and complete all required visits
9. Willingness to participate in the study by signing the Informed Consent Form (ICF)

Exclusion criteria:
Participant exclusion criteria as of 05/12/2018:
General Exclusion Criteria:
1. Participants not able to give consent
2. Participants who are unable to understand the nature, scope, significance and consequences of this clinical trial
3. Participants taking any concomitant medication
4. Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical struc-ture (moxifloxacin or any member from the quinolone class, rifapentine or any member of the rifamycins, doxycycline or any member of the tetracyclines)
5. Simultaneous participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
6. Participants with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial
7. Known or persistent abuse of medication, drugs or alcohol

Exclusion criteria regarding special restrictions for females:
1. Pregnant women
2. Breastfeeding women
3. Females of childbearing potential, who are not willing or able to use methods to prevent a pregnancy for the entire treatment duration in addition to hormonal contraception (e.g. condoms) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases.

Indication specific exclusion criteria:
1. History or clinical signs of tuberculosis or treatment against TB
2. History of porphyria
3. History or clinical signs of arrhythmia
4. Bradycardia (< 50bpm)
5. QT-prolongation (QT interval >440 msec for men and >460 msec for women)
6. History of tendinitis or tendon rupture
7. History of rheumatoid arthritis
8. History of myasthenia gravis or polio
9. History of cerebral disorder (e.g. epilepsy)
10. History of photosensitivity/phototoxicity
11. History of Diabetes mellitus (in addition urine examination for glucose)
12. Evidence of clinically significant neurological, cardiac, pulmonary, hepatic or renal disease as far as can be assessed by history of participants, physical examination, and/or laboratory examinations
13. Evidence of acute Hepatitis A and of acute or chronic Hepatitis B or C
14. Laboratory evidence of liver disease (AST, ALT, gammaGT, Bilirubin greater than the upper limit of normal)
15. Laboratory evidence of renal disease (serum creatinine greater than 1.5 times upper limit of normal)
16. Laboratory evidence of low or high potassium level (potassium level < 3.6 or > 5.2)
17. Laboratory evidence of leucopenia (< lower limit of normal)


Previous participant exclusion criteria:
1. Pregnant women
2. Breastfeeding women
3. Participants not able to give consent
4. Participants without legal capacity who are unable to understand the nature, scope, significance and consequences of this

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Onchocerciasis (River blindness)
Infections and Infestations

Intervention(s)

1. Experimental interventions:
Treatment regimen 1: Moxifloxacin 400mg/d plus rifapentine 900mg/d for 14 days (oral)
Treatment regimen 2: Moxifloxacin 400mg/d plus rifapentine 900mg/d for 7 days (oral)

2. Control interventions:
Treatment regimen 3: (Standard therapy): Doxycycline 200mg/d for 4 weeks (oral)
Treatment regimen 4: ("negative control"): No treatment but nodulectomy after 6 months

Additional treatment:
All participants (experimental and control interventions) will be treated with ivermectin (Mectizan®) at the standard MDA (mass drug administration) dosage of 150 µg/kg following the nodulectomies 6 months after study onset.

All treatment regimens will be administered by the trial clinician directly in the villages of the participants in form of daily observed treatment (DOT).

Follow-up per patient:
Onchocercomata will be removed under local anaesthesia in the hospital (nodulectomy) to assess Wolbachia, worm vitality and embryogenesis. The nodulectomies will be performed 6 months after the start of drug administration since Wolbachia depletion is completed after 4-5 months. Patients will be kept in hospital for the day of operation or one day longer (depending on the number of nodules ectomised) for observation before being discharged. Wound dressing will continue in the villages until all the wounds are healed (at least for 10 days after nodulectomy).

Primary Outcome(s)

Primary outcome measure as of 05/12/2018:
Absence of Wolbachia endobacteria in female adult worms assessed by immunohistology 6 months after treatment onset.

Previous primary outcome measure:
Absence of Wolbachia endobacteria in adult worms assessed by immuno-histology 6 months after treatment onset.

Secondary Outcome(s)

Secondary outcome measures as of 05/12/2018:
1. Reduction of Wolbachia bacteria in adult worms assessed by PCR 6 months after treatment onset.
2. Absence of Wolbachia bacteria in adult worms assessed by PCR 6 months after treatment onset.
3. Evaluation of worm embryogenesis assessed by histology in onchocercoma sections 6 months after treatment onset:
3.1. Normal embryos
3.2. Degenerated embryos
3.3. No embryos/uterus empty
4. Reduction of microfilariae in the skin 3.5 and 6 months after treatment onset.
5. Absence of microfilariae in the skin 3.5 and 6 months after treatment onset.
6. Reduction of the Wolbachia in the skin Mf 3.5 and 6 months after treatment onset assessed by PCR.
7. Adverse events (AEs) as well as serious adverse events (SAEs) in response to the different treatments will be assessed and described in the scope of the daily observed treatment (DOT).


Previous secondary outcome measures:
1. Reduction of Wolbachia bacteria in adult worms assessed by PCR 6 months after treatment onset
2. Absence of Wolbachia bacteria in adult worms assessed by PCR 6 months after treatment onset
3. Reduction of microfilariae in the skin 6 months after treatment onset
4. Absence of microfilariae in the skin 6 months after treatment onset
5. Evaluation of worm embryogenesis assessed by histology 6 months after treatment onset:
5.1. Normal embryos
5.2. Degenerated embryos
5.3. No embryos
6. Assessment of safety: Adverse events (AEs) will be assessed and described in the scope of the daily observed treatment (DOT):
6.1. Occurrence of an AE
6.2. Intensity of AE (Grade 0 (None); Grade 1 (Mild): No effect on activities of daily life; Grade 2 (Moderate): Daily life activities are partially limited (can complete = 50% of necessary activities); Grade 3 (Severe): Daily life activities are severely restricted (can complete < 50% of necessary activities))
6.3. SAE?
6.4. Relation to treatment (definite, probable, possible, remote, not related)
6.5. Intervention
6.6. Outcome of AE (resolved spontaneously, resolved with treatment, resolved with residual effect, unchanged/ not resolved, death)

Secondary ID(s)

BONFOR 2014-11B-02

Source(s) of Monetary Support

BONFOR Research Commission of the Medical Faculty at Bonn University (Germany), Commission for Clinical Trials of the University Hospital Bonn (Germany)

Ethics review

Status:
Approval date:
Contact:

Ethics approval as of 05/12/2018: 1. The Committee for Human Research, Publication and Ethics (CHRPE) of the Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana: approval: 22/11/2016; renewal: 04/05/2018 2. The Ghana Health Service Ethics Review Committee (GHS-ERC), Accra, Ghana: approval: 30/05/2017; renewal: 31/05/2018 3. The Ghana Food and Drug Authority (Ghana FDA), Accra, Ghana: approval:

Results

• Results available: Yes
• Date Completed: 31/12/2019