| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Respiratory Syncytial Virus Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| RSV is a common virus that can cause severe chest infections in small children, adults with heart, lung and immune system conditions and elderly people. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061603 |
| E.1.2 | Term | Respiratory syncytial virus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine if a single, intravenous (IV) dose of MK-1654 when administered at 1 of 4 dose levels results in a reduction in viral load after intranasal inoculation (with respiratory syncytial virus subgroup A [RSV A] Memphis 37b) compared to IV placebo |
|
| E.2.2 | Secondary objectives of the trial |
1. To estimate the effect of each of the 4 dose levels of IV MK-1654 on the incidence of symptomatic RSV infection after intranasal inoculation (with RSV A Memphis 37b) compared to IV placebo
2. To evaluate the safety and tolerability of increasing doses of IV MK-1654 compared to IV placebo
3. To estimate the MK-1654 serum concentration after administration of increasing doses of IV MK-1654
4. To estimate RSV serum neutralizing antibody titers after administration of IV MK-1654 compared to IV placebo and after intranasal inoculation (with RSV Memphis 37b) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. In good health with no history of major medical conditions that will interfere with subject safety, as defined by medical history, physical examination (including vital signs), ECG, and routine laboratory tests and determined by the Investigator at a screening evaluation.
2. Participants will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening.
Demographics
3. Participant is male or female.
4. Participant is from 18 years to 55 years of age inclusive, at the time of signing the study specific informed consent.
5. A total body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 30kg/m2.
Male Participants
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
6. Male participants must agree to the contraceptive requirements below at dosing and continuing until 90 days after dosing/28 days after viral inoculation – whichever is later.
• Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent exposure of any partner (male and female) to the IMP.
• Male sterilisation with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate (please note that the use of condom with spermicide will still be required to prevent partner exposure). This applies only to males participating in the study.
• In addition, for female partners of child bearing potential, that partner must use another form of contraception such as one of the highly effective methods mentioned below for female participants.
• True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
In addition to the contraceptive requirements above, male participants must agree not to donate sperm until 90 days after the date of dosing.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. Female participants of childbearing potential must have a negative pregnancy test at screening and prior to dosing.
Female participants of childbearing potential must use one form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to dosing. The contraception use must continue until 30 days after dosing/28 days after the date of viral inoculation - whichever is later. Highly effective contraception is as described below:
• Established (a minimum of 2 weeks prior to dosing) use of hormonal methods of contraception described below.
1. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
1) oral
2) intravaginal
3) transdermal
2. progestogen-only hormonal contraception associated with inhibition of ovulation:
1) oral
2) injectable
3) implantable
Note: when hormonal methods of contraception are used, male partners are required to use a condom with a spermicide.
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• Bilateral tubal ligation
• Male sterilisation (with the appropriate written documentation from the participant to confirm the vasectomy) where the vasectomised male is the sole partner for that woman.
• True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
8. Female participants who are no longer of child bearing potential.
• Women no longer of child bearing potential (post-menopausal females are defined as having a history of amenorrhea for at least 12 months with no alternative medical cause, otherwise they should have documented status as being surgically sterile or post hysterectomy (e.g. tubal ligation, hysterectomy, bilateral salpingectomy and bilateral oophorectomy) and/or by FSH level >40 IU/mL, confirmed by laboratory).
Informed Consent
9. The participant provides written informed consent/assent for the study, including for future biomedical research.
Additional Categories
10. Serosuitable* to the challenge virus within 90 days of IMP dosing.
* The serology result obtained suggests that the subject is sensitive to RSV infection, i.e. they are likely to be infected following inoculation with the challenge virus.
|
|
| E.4 | Principal exclusion criteria |
Medical Conditions
1. Females who: Are breastfeeding or have been pregnant within 6 months prior to the study enrollment.
2. Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological (including immunesuppression), metabolic, urological, renal, neurological, or psychiatric disease (including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis; participants with a history of depression of any severity within the last 2 years prior to IMP dosing should only be included if the PHQ-9 score is less than or equal to 4). The following conditions apply:
• Participants with clinically mild atopic eczema/atopic dermatitis and clinically mild psoriasis may be included at the Investigator's discretion (e.g., if small amounts of regular topical steroids are used, no eczema in cubital fossa; moderate to large amounts of daily dermal corticosteroids is an exclusion).
• Rhinitis (including hay fever) which is clinically active or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of IMP dosing. Participants with a history of currently inactive rhinitis (within the last 30 days) or mild rhinitis may be included at the PI’s discretion.
• Participants with a physician diagnosed underactive thyroid who have been controlled on treatment for at least 6 months with evidence of a normal thyroid function test (TFT) can be included at the discretion of the PI.
• Any concurrent serious illness including history of malignancy that may interfere with the aims of the study or a subject completing the study. Basal cell carcinoma within 5 years of initial diagnosis or with evidence of recurrence is also an exclusion.
• Participants reporting physician diagnosed migraine can be included as long as there are not associated neurological symptoms such as hemiplegia or visual loss. Cluster headache/migraine or prophylactic treatment for migraine is an exclusion.
• Participants with physician diagnosed mild Irritable Bowel Syndrome (IBS) not requiring regular treatment can be included at the discretion of the PI.
3. Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral inoculation, (historical nasal polyps can be included, but large nasal polyps causing current and significant symptoms and/or requiring regular treatments in the last month will be excluded).
4. Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months prior to IMP dosing and/or history of being hospitalized due to epistaxis on any previous occasion.
5. History or currently active symptoms suggestive of upper or lower respiratory tract infection within 6 weeks prior to IMP dosing.
6. And/or other major disease that, in the opinion of the Investigator, may interfere with a subject completing the study and necessary investigations.
7. History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
8. Confirmed positive test for drugs of abuse prior to randomization.
9. History or presence of alcohol addiction, or excessive use of alcohol (weekly intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small glass of wine or a measure of spirits), or excessive consumption of xanthine containing substances (e.g. daily intake in excess of 5 cups of caffeinated drinks e.g. coffee, tea, cola).
10. Is positive for human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test..
Prior/Concomitant Therapy
11. Evidence of receipt of vaccine within the 4 weeks prior to IMP dosing.
12. Intention to receive any vaccine(s) before the last day of Follow-up. (NB. No travel restrictions will apply after the poststudy visit).
13. Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more of blood during the 3 months prior IMP dosing or planned during the 3 months after the final visit.
14. Use within 7 days prior to IMP dosing of any medication or product (prescription or over-the-counter), for symptoms of hay fever, dermatitis, nasal congestion or respiratory tract infections including the use of regular nasal or dermal corticosteroids or antibiotics, apart from those described and allowed in exclusion criteria 2.
15. Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to IMP dosing.
[Please refer to clinical protocol for a full list of exclusion criteria]. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Area Under Viral Load-time Curve (VL-AUC) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40) |
|
| E.5.2 | Secondary end point(s) |
1. Incidence of Symptomatic RSV Infection
2. Number of Participants with an Adverse Event (AE)
3. Number of Participants with a Serious Adverse Event (SAE)
4. Serum Concentration of MK-1654
5. Concentration of RSV Serum Neutralizing Antibody Titers |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40)
2. Up to 180 days
3. Up to 180 days
4. Days 1, 8, 15, 29, 40, and 57
5. Days 1, 29, 40, and 57 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 8 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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