| Eligibility |
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:
1. Abrupt dramatic onset of OCD meeting DSM-5 diagnostic criteria for OCD as
confirmed by the MINI-KID-7
2. 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
3. Signed informed consent of patient's legal representative(s)/guardians(s). If patients
are old enough to understand the risks and benefits of the study (as determined by
each institution), they should provide written assent/consent.
4. Legal representative(s)/guardians(s) must be capable of understanding and complying
with the relevant aspects of the study protocol.
Patients who will additionally meet the following optional inclusion criteria will be
identified as patients with Pediatric autoimmune neuropsychiatric disorders associated with
streptococcal infection (PANDAS):
1. An episodic (relapsing-remitting) course of symptom severity
2. Temporal association between symptoms onset or exacerbation and infections with group
A streptococcal infection (GAS, positive throat culture and/or anti-GAS antibody
titers)
Exclusion Criteria
1. Onset of current PANS episode more than 12 months prior to first investigational
medicinal product (IMP) treatment.
2. a. In patients with relapsing episodes: Onset of initial PANS episode more than 24
months prior to first IMP treatment.
b. In patients with relapsing episodes: Absence of significant improvement and
stabilization between the episodes according to investigator's judgment.
3. Contraindication to receiving intravenous immunoglobulin (IVIG), including:
1. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response,
to immunoglobulin, blood or plasma derived products, or any component of Panzyga.
2. Immunoglobulin (Ig) A deficiency with antibodies to IgA (<7 mg/dL).
3. Hyperviscosity syndromes or known or suspected hypercoagulable conditions as
inferred from clinical history, which can increase risks of thrombosis associated
with IVIG administration.
4. History of arterial or venous thrombotic or thromboembolic events (TEEs) within
the last year prior to Baseline. History of acquired or inherited thrombophilia
any time prior to Baseline.
5. Need for live virus vaccine within three months after receiving study drug.
6. Renal dysfunction (creatinine >120 µmol/L or 1.36 mg/dL), history of renal
dysfunction, or known risk factor for renal dysfunction (chronic renal
insufficiency, diabetes mellitus, taking known nephrotoxic medication). For
Italy, estimated glomerular filtration rate (eGFR) needs to be calculated with
the 2009 Schwartz equation (eGFR = k * height/Serum creatinine (Scr), where k is
0.413) [2]. eGFR must not be below 30.
4. Severely restricted food intake likely to require parenteral nutrition, and <5th
percentile BMI-for-age (BMI Percentile Calculator for Child and Teen based on Centers
for Disease Control and Prevention growth charts for children and teens ages 2 through
19 years)
5. Body mass index = 40 kg/m2
6. Presence of symptoms consistent with autism or schizophrenia, bipolar disorder, or
other psychotic disorder (unless psychotic symptoms have onset coincident with PANS).
7. Presence of serious or unstable medical illness, psychiatric (e.g. high suicide risk)
or behavioral symptoms that would make participation unsafe or study procedures too
difficult to tolerate.
8. Treatment with systemic corticosteroids within eight weeks before randomization.
9. Treatment with NSAIDs within five days before randomization.
10. Treatment with melatonin within one week before randomization
11. History of rheumatic fever, including SC (neurological manifestation).
12. Past treatment of neuropsychiatric symptoms with immunomodulatory therapy (such as
IVIG, rituximab or mycophenolate mofetil) or plasmapheresis.
13. Initiation of cognitive behavioral therapy (CBT) within eight weeks before
randomization.
14. Start of treatment or change in dosing with selective serotonin reuptake inhibitors
[SSRIs] within eight weeks before randomization.
15. Treatment with alpha-2 agonists or antipsychotics within eight weeks before
randomization.
16. Start of treatment or change in dosing with stimulants (Methylphenidate, Amphetamine
and similar products) for Attention-Deficit Hyperactivity Disorder (ADHD) within four
weeks prior to randomization.
17. Active use of tetrahydrocannabinol (THC) containing agents within four weeks prior to
enrollment or during the trial. Use of cannabidiol- (CBD) / cannabimovone- (CBM)
containing agents without THC is allowed if started more than eight weeks before
enrollment in a stable dose/frequency.
18. Use of antibiotics or antiviral drugs at therapeutic dose within one week before
randomization. Use of antibiotics at a prophylactic dose is allowed if started at
least four weeks before randomization (Section 4.2).
19. Severe liver disease (alanine aminotransferase [ALT] three times above normal value).
20. Known hepatitis B, hepatitis C or HIV infection as per patient medical history.
21. Cardiac insufficiency (New York Heart Association [NYHA] classification III-IV),
cardiomyopathy, significant cardiac dysrhythmia requiring treatment.
22. Medical conditions with symptoms and effects that could alter protein catabolism
and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
23. Pregnant and/or lactating women.
24. Female patients of childbearing potential unwilling to use a protocol-required method
of contraception (as per protocol Section 7.3.9 b) from Screening throughout the study
treatment period and for four weeks following the last dose of study drug. A woman of
childbearing potential is defined as a fertile woman or adolescent, from the beginning
of menstruation, unless permanently sterile.
25. Participation in another interventional clinical trial that is either blinded or
involves an investigational (not approved) product within three months before Baseline
or during the course of the clinical study. Participation in observational clinical
trials or open-label trials involving an approved product may be permitted after
consultation with the medical monitor.
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