Arimoclomol Prospective Study in Participants Diagnosed With Niemann-Pick Disease Type C

Prior treatment

• Recipient of a liver transplant or planned liver transplantation;
• 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;
• For participants who have not completed the CT-ORZY-NPC-001 study, fulfilling any of the criteria listed below:
  • Participants 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 participants 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 participants;
  • Severe manifestations of NP-C disease that would interfere with the participant's ability to comply with the requirements of this protocol;
  • Treatment with any IMP within 4 weeks prior to the study enrolment.

Other illness

• Known or suspected allergy or intolerance to the IMP (arimoclomol or constituents);
• In the opinion of the Investigator, the participant's clinical condition does not allow for the required blood collection and/or skin biopsies as per the protocol-specified procedures;

Lab values

• 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);

Other

• 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);

• EITHER NP-C participants who have entered the CT-ORZY-NPC-001 study and who have completed Visit 2 (EOS) of the CT-ORZY-NPC-001 study.
• OR
• NPC participants who did not enter or complete the CT-ORZY-NPC-001 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 participant 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 CT-ORZY-NPC-002 study;
  • o If a participant 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 participants 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 participants 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 participants of child-bearing potential) and for 3 months after the last dose of IMP (for male participants 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 participant.
  • •Ability to comply with the protocol-specified procedures/evaluations and scheduled visits.