Arimoclomol an Patienten mit diagnostizierter Niemann-Pick-Krankheit Typ C

Drug: arimoclomol;Drug: Placebo

Inclusion Criteria:

EITHER NP-C patients who have entered the CTORZYNPC001 study and who have completed Visit 2
(EOS) of the CTORZYNPC001 study.

OR

NPC patients who did not enter or complete the CTORZYNPC001 study but are fulfilling all of
criteria listed below:

?Diagnosis of NPC1 or NPC2;

NPC diagnosis confirmed by:

- Genetically confirmed (deoxyribonucleic acid [DNA] sequence analysis) by mutations in
both alleles of NPC1 or NPC2, OR

- Mutation in only one allele of NPC1 or NPC2 plus either positive filipin staining or
elevated cholestane triol/oxysterols (>2 x upper limit of normal).

- Males and females aged from 2 years to 18 years and 11 months;

- Treated or not treated with miglustat;

- If a patient is under prescribed treatment with miglustat, it has to be under
stable dose of the medication for at least 6 continuous months prior to inclusion
in the CTORZYNPC002 study;

o If a patient has been discontinued from prescribed treatment with miglustat,
they must have been discontinued for at least 3 continuous months prior to
inclusion in the CT-ORZY-NPC-002 study;

- Body mass index (BMI) Z score = -2 SD (standard deviation) for age, according to
the World Health Organisation (WHO) standards;

- Presenting at least one neurological symptom of the disease (for example, but not
limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia,
dystonia, seizures, dysarthria, or dysphagia);

- Ability to walk either independently or with assistance.

- Written informed consent (and assent if appropriate to local laws and
regulations) prior to any study-related procedures;

- Willing to participate in all aspects of trial design including blood
sampling (PK, blood biomarkers and safety labs), skin biopsies and imaging
(ultrasonography of the liver and spleen);

- Ability to travel to the corresponding clinical trial site at the scheduled
visit times for evaluation and follow-up;

- All sexually active female patients of child-bearing potential
(post-menarchal) must use highly effective contraception during the study
and until 1 week after the last dose of IMP.

Highly effective birth control methods include: Combined (oestrogen and progestogen
containing) hormonal contraception associated with inhibition of ovulation (oral,
intravaginal or transdermal); progestogen-only hormonal contraception associated with
inhibition of ovulation (oral, injectable or implantable); intrauterine device (IUD);
intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; and vasectomised
partner.

All sexually active male patients with female partners of child-bearing potential
(post-menarchal) must use a condom with or without spermicide in addition to the birth
control used by their partners during the study and until 3 months after the last dose of
IMP.

Sexual abstinence is considered a highly effective birth control method only if it is
defined as refraining from heterosexual intercourse during the study and for 1 week after
the last dose of IMP (for female patients of child-bearing potential) and for 3 months
after the last dose of IMP (for male patients with female partners of child-bearing
potential). The reliability of sexual abstinence needs to be evaluated by the Investigator
in relation to the duration of the clinical trial and the preferred and usual lifestyle of
the patient.

•Ability to comply with the protocol-specified procedures/evaluations and scheduled visits.

Exclusion Criteria:

- Recipient of a liver transplant or planned liver transplantation;

- Severe liver insufficiency (defined as hepatic laboratory parameters, AST and/or ALT
greater than three-times the upper limit of normal for age and gender (central
laboratory assessment);

- Renal insufficiency, with serum creatinine level greater than 1.5 times the upper
limit of normal (central laboratory assessment);

- Known or suspected allergy or intolerance to the IMP (arimoclomol or constituents);

- In the opinion of the Investigator, the patient's clinical condition does not allow
for the required blood collection and/or skin biopsies as per the protocol-specified
procedures;

- Treatment with any investigational drug during the study or in the 4 weeks prior to
entering the study.

This includes treatment with any investigational drug during the study in an attempt to
treat NP-C;

- Pregnancy or breastfeeding;

- Current participation in another trial is not permitted unless it is a
non-interventional study and the sole purpose of the trial is for long-term follow
up/survival data (registry);

- For patients who have not completed the CTORZYNPC001 study, fulfilling any of the
criteria listed below:

- Patients with uncontrolled severe epileptic seizures period (at least 3
consecutive severe epileptic seizures that required medication) within 2 months
prior to the written consent. This includes patients with ongoing seizures that
are not stable in frequency or type or duration over a 2 month period prior to
enrolment, requiring change in dose of antiepileptic medication (other than
adjustment for weight) over a 2 month period prior to enrolment, or requiring 3
or more antiepileptic medications to control seizures;

- Neurologically asymptomatic patients;

- Severe manifestations of NP-C disease that would interfere with the patient's
ability to comply with the requirements of this protocol;

- Treatment with any IMP within 4 weeks prior to the study enrolment.