E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). PANS is a research diagnosis given to patients who have an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction, and several other neuropsychiatric symptoms. |
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E.1.1.1 | Medical condition in easily understood language |
PANS is a research diagnosis given to patients with an acute onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction, and several other neuropsychiatric symptoms. |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
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 |
The primary objective of this study is to confirm that Panzyga is superior to placebo (0.9% w/v sodium chloride) for reducing the severity of symptoms associated with PANS in pediatric patients. |
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E.2.2 | Secondary objectives of the trial |
- to verify the sustainability of the reduction of the severity of symptoms in pediatric patients treated with Panzyga - to assess the efficacy of Panzyga treatment in reducing functional impairment associated with PANS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients ≥6 to ≤17 years of age. 2. Confirmed diagnosis of moderate to severe PANS with prominent and stable obsessive-compulsive disorder (OCD) symptoms (i.e. Clinical Global Impression (CGI)—Severity-OCD rating of ≥ 4 or higher on 2 ratings without a change of more than 1 unit between measurements) based on the following criteria : a. Abrupt dramatic onset of OCD meeting DSM-5 diagnostic criteria for OCD as confirmed by the MINI-KID-7 b. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least two of the following seven categories, that are not better explained by a known neurologic or medical disorder, such as Sydenham chorea (SC), systemic lupus erythematosus, Tourette disorder, or other: • Anxiety (particularly, separation anxiety) • Emotional lability (extreme mood swings) and/or depression • Irritability, aggression and/or severely oppositional behaviors • Behavioral (developmental) regression (examples, talking baby talk, throwing temper tantrums, etc.) • Deterioration in school performance Sensory or motor abnormalities • Somatic signs and symptoms, including sleep disturbances, bed wetting or urinary frequency
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E.4 | Principal exclusion criteria |
1. Onset of initial PANS symptoms more than six months prior to Screening. In patients with relapsing symptoms, initial symptoms may not have been more than 12 months prior to Screening, must have fully resolved based on investigator’s judgment, and their recurrence must be less than 6 months prior to Screening. 5. Presence of symptoms consistent with autism or schizophrenia, bipolar disorder, or other psychotic disorder. 7. Treatment with systemic corticosteroids within eight weeks before randomization. 8. History of rheumatic fever, including SC (neurological manifestation). 9. Past treatment of neuropsychiatric symptoms with immunomodulatory therapy (such as systemic corticosteroids, IVIG or plasmapheresis). 10. Initiation of cognitive behavioral therapy (CBT) within eight weeks before randomization. 11. Start of treatment or change in dosing with selective serotonin reuptake inhibitors [SSRIs] within eight weeks before randomization. Treatment with alpha-2 agonists or antipsychotics within eight weeks before randomization. 12. Completion of antibiotics or antiviral drugs course for acute infection within one week before randomization. Use of antibiotics at a prophylactic dose is allowed if started at least eight weeks before randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
CY-BOCS score - Primary [ Time Frame: 9 weeks ] Improvement of neuropsychiatric symptomatology and behavior in PANS patients determined by clinician-rated Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score. The mean changes in the total CY-BOCS score from Baseline to Week 9 will be compared between Panzyga and placebo treatment to demonstrate superiority. The CY-BOCS scale score is a clinician-rated, semi-structured interview for rating the presence or absence, as well as the severity of obsessive-compulsive symptoms.The CY-BOCS yields a total obsession score, a total compulsion score and combined total score (maximum total CY-BOCS score=40). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- CY-BOCS score - Secondary [ Time Frame: 18 weeks ] CY-BOCS score at the end of the follow-up period at Week 18 will be compared to the Week 9 scores within the (Panzyga - Placebo) treatment sequence group - Clinical Global Impression [ Time Frame: 18 weeks ] To assess behavioral changes via the Clinical Global Impression (CGI) assessment. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1 = normal; not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. The Clinical Global Impression - Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and is rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. - Parent OC Impact Scale [ Time Frame: 18 weeks ] To assess behavioral changes via the Parent OC Impact Scale - COIS-RP assessment. The Child Obsessive-Compulsive Impact Scale-Revised consists of parallel 33-item parent and child-report versions assessing impairment due to OCD across multiple functional domains. Items are rated on a 4-point scale from 0 (not at all) to 3 (very much). - Child OC Impact Scale [ Time Frame: 18 weeks ] To assess behavioral changes via the Child OC Impact Scale COIS-RC assessment. The Child Obsessive-Compulsive Impact Scale-Revised consists of parallel 33-item parent and child-report versions assessing impairment due to OCD across multiple functional domains. Items are rated on a 4-point scale from 0 (not at all) to 3 (very much). - SNAP-IV 26 item Scale [ Time Frame: 18 weeks ] To assess behavioral changes via the Swanson, Nolan, And Pelham Scale - Version IV (SNAP-IV) 26 item Scale. It is a 26-item, parent- or teacher-reported scale which elicits reporting on each of the DSM cardinal symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) in children and adolescents. The 26-item scale also includes items on aggression, mood, and school performance and behavior. It is used extensively in ADHD and disruptive behavior disorder intervention trials and is sensitive to change - Parent Tic Questionnaire (PTQ) [ Time Frame: 18 weeks ] To assess behavioral changes via the Parent Tic Questionnaire (PTQ). The PTQ assesses tic severity in the past week, allowing for individual parent ratings of tic presence or absence. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Quadruple blinded (Participant, Care Provider, Investigator, Outcomes Assessor) |
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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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |