A study of PQ912 in patients with Alzheimer's Disease.

Phase 1

• Conditions: Early Stage Alzheimer's Disease; MedDRA version: 19.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 19.0Level: PTClassification code 10074616Term: Prodromal Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-001967-11-DE
• Lead Sponsor: Probiodrug AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-06
• Last Update Posted: 9 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. Signed and dated written informed consent obtained from the subject in accordance with local regulations.
2. Male or surgically sterile or postmenopausal female, aged =50 to =89 years. Male subjects with childbearing potential partners are willing to
and should use condoms during study medication treatment and until 28 days after the last dose of study medication.
3. Diagnosis of MCI due to AD or mild dementia due to AD with amnestic presentation, according to Alzheimer Association – National Institute on Aging (AA-NIA) criteria [Albert et al 2011; McKhann et al 2011].
4. MMSE score of 21 to 30 inclusive at screening.
5. Screening visit brain MRI scan consistent with the diagnosis of MCI due to AD or mild dementia due to AD, as judged by central rater.
6. A positive AD signature showing one of the following (either a, b, c, OR d):
a. Screening CSF sample with an A-beta 42 concentration of less than 638 ng/L AND total tau >375 ng/L, as assessed by central laboratory.
b. Screening CSF sample with an A-beta 42 concentration of less than 638 ng/L AND p-tau > 52 ng/L, as assessed by central laboratory.
c. Tau/A-beta ratio > 0.52, as assessed by central laboratory.
d. Positive amyloid PET if available prior to screening.
7. Treatment naïve, this means not having received any prior established specific treatment for MCI due to AD or mild dementia due to AD including no (prior) use of an acetylcholinesterase inhibitor, or memantine. A maximum of two months of prior cumulative treatment with an acetylcholinesterase inhibitor or memantine is allowed if the acetylcholinesterase inhibitor or memantine was discontinued due to intolerance and if this was done at least two months prior to baseline.
Use of Souvenaid will be allowed if Souvenaid was discontinued at least two months prior to baseline, or if the subject is on stable dose for at least six months prior to baseline and is willing to continue during the study on the same dose and frequency.
8. Fluency in local language and evidence of adequate premorbid intellectual functioning in the opinion of the investigator.
9. Adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the investigator.
10. Outpatient with study partner (age 18 years or older) capable of accompanying the subject on all clinic visits. In accordance to Swedish regulations the availability of a study partner is not applicable for Sweden.
11. The subject and study partner are likely to be able to participate in all scheduled evaluations. In accordance to Swedish regulations the availability of a study partner is not applicable for Sweden.
12. In the opinion of the investigator, the subject and study partner can be compliant and have a high probability of completing the study. In accordance to Swedish regulations the availability of a study partner is not applicable for Sweden.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

Exclusion Criteria

1. Significant neurologic disease, other than AD, that may affect cognition.
2. Atypical clinical presentations of MCI due to AD or mild dementia due to AD, such as the visual variant of AD (incl. posterior cortical atrophy) or the language variant (including logopenic aphasia).
Concomitant disorders:
3. History of or screening visit brain MRI indicative of any other significant abnormality, incl. but not limited to multiple microhaemorrhages (4 or more, defined as 10 mm or less at the greatest diameter), severe white matter hyper intensities (Fazekas score 3), history or evidence of a single prior haemorrhage >1 cm3, multiple lacunar infarcts or evidence of a single prior infarct >1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space-occupying lesions (e.g. brain tumours).
4. Current presence of a clinically important major psychiatric disorder (e.g. major depressive disorder) defined by DSM-5 criteria, or symptom(s) (e.g. hallucinations) that could affect subject’s ability to complete the study.
5. Current clinically important systemic illness, likely to result in clinically relevant deterioration of the subject’s condition or might affect the subject’s safety.
6. History of clinically evident stroke or history of clinically important and symptomatic carotid or vertebrobasilar stenosis or plaque.
7. History of seizures within the last 2 yrs prior to screening.
8. Weight > 120 kg at screening.
9. Myocardial Infarction within the last 6 months prior to screening.
10. History of cancer within last 2 years prior to screening, except for the following: non-metastatic basal cell carcinoma, and squamous cell carcinoma of the skin or any other cancer, if evidence of no residual cancer has been confirmed within the last 6 months before baseline.
11. History of uncontrolled hypertension (in the opinion of the investigator) within 6 months prior to screening.
12. Other clinically important diseases or conditions compromising the study or the subject’s safety.
13. Hb <11 g/dL at screening.
14. Clinically important infection within 30d prior to screening.
15. Hypersensitivity to excipients in test article.
16. Severe hepatic failure (Child-Pugh C) or kidney failure (creatinine clearance (eGFR) = 30 ml/min/1.73m2) or creatinine >1.5x ULN or AST or ALT > 3xULN at screening.
Concomitant Medication/Therapies:
17. The following therapies are not permitted prior to baseline and until V5/EOT:
- Anticoagulants within 30d prior to baseline.
NOTE: Platelet anti-aggregants (e.g. clopidogrel bisulfate or the use of carbasalate calcium 100 mg/day, or aspirin 325 mg/day or less) are allowed if stable dose for at least 30d prior baseline. Combination of clopidogrel and carbasalate calcium or aspirin is not allowed during lumbar puncture.
- Use of experimental meds for AD or any other investigational drugs/devices for treatment of indications other than AD within 60d prior to baseline.
- Treatment with an ACE inhibitor or memantine or Souvenaid, except for an ACE inhibitor in case of clinically relevant worsening of cognitive performance during the double blind study period, and for Souvenaid if only on stable dose for at least 6 weeks prior to baseline.
- Treatment with immunosuppressants (e.g. systemic corticosteroids > 10 mg/day) within the last 90d prior to baseline (topical + nasal corticosteroids and inhaled corticosteroids for asthma are permitted).
- Chemotherapy for malignancy within la

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified