Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000964718
Ethics application status
Approved
Date submitted
22/06/2022
Date registered
7/07/2022
Date last updated
2/05/2023
Date data sharing statement initially provided
7/07/2022
Date results information initially provided
2/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 trial assessing the Safety, Tolerability, and Pharmacokinetics of NIDO-361 in Healthy Male Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Single and Multiple Ascending Doses of NIDO-361 in Healthy Male Subjects
Secondary ID [1] 307305 0
NIDO-361-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal and bulbar muscular atrophy (SBMA) 326596 0
Condition category
Condition code
Neurological 323843 323843 0 0
Other neurological disorders
Musculoskeletal 323918 323918 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two parts.
Part A: A single ascending dose (SAD) part where dose levels will be evaluated in a sequential manner starting at the proposed lowest dose level in healthy male volunteers.
40 healthy male volunteers will be enrolled in a total of 5 cohorts. Each cohort will enrol 8 participants with 6 participants randomized to receive NIDO-361 and 2 participants randomized to receive placebo.
NIDO-361 will be provided as an oral capsule. NIDO-361 dose levels in the range of 75 to 500 mg are planned to be investigated.
A single dose of NIDO-361 or placebo will be administered on Day 1 followed by approximately 48 hours of safety, tolerability, and PK assessments. Participants will return approximately 1 week post study check-out to complete follow-up assessments.
Part B: A multiple ascending dose (MAD) part where dose levels will be evaluated depending on SAD results in healthy male volunteers.
Up to 24 healthy male volunteers will be enrolled in a total of 3 cohorts. Each cohort will enrol 8 participants with 6 participants randomized to receive NIDO-361 and 2 participants randomized to receive placebo. A dose level will only be evaluated in Part B if determined to be safe and tolerable in Part A.
NIDO-361 or placebo will be administered daily (QD) for seven days (total of 7 doses) followed by approximately 48 hours of observation after last dose for safety assessments before discharge. Participants will return approximately 1 week post study check-out to complete follow-up assessments.

Adherence to the intervention will be done via completion of drug accountability.
Intervention code [1] 323754 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules are size 3 or size 0 Swedish orange hydroxypropyl methylcellulose capsules comprising an orange body and cap with no markings. Placebo will be identical in appearance to NIDO-361 capsules and administered orally.
Control group
Placebo

Outcomes
Primary outcome [1] 331637 0
To determine the safety and tolerability of NIDO-361 when administered as a single oral dose in healthy male subjects.

Safety Endpoints Include: Adverse Events (AEs), concomitant medications, physical examinations (including neurological examination, vital signs, weight, 12-lead ECG), and clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis).
Timepoint [1] 331637 0
Adverse Events: Assessed daily at Screening, Day -1 (Check-in), Day 1, Day 2, Day 3 (Check-out), Day 8 (End of Study)/Early Termination Visit. Adverse Events will be graded using The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will not be assessed daily from Days 3-7. Following Day 3 (Check-Out), participants will return to clinic on Day 8 and final study visit will be conducted, including review of any AEs participants may have experienced after being discharged from clinic on Day 3 (Check-Out).

Concomitant Medications: Assessed daily at Screening, Day -1 (Check-in), Day 1, Day 2, Day 3 (Check-out), Day 8 (End of Study)/Early Termination Visit. Site staff will question participants on use of concomitant medications at study visits.

Physical Examinations: General appearance; head, ears, eyes, nose (HEENT), and throat examination, neck (including thyroid and nodes); cardiovascular, respiratory, gastrointestinal, renal, neurological, and musculoskeletal systems; and skin will be assessed. Complete physical examination will be performed at Screening and Day 8 (End of Study)/Early Termination Visit.. Symptom directed physical examination will be performed at Day -1 (Check-in) and Day 3 (Check-out).

Vital Signs: Blood pressure and heart rate are assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day -1 (Check-in), Day 1 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post-dose, Day 2 24 hrs and 36 hrs post-dose, Day 3 48 hrs post-dose, Day 8 (End of Study)/Early Termination Visit.

Weight: Assessed using scales at Screening, Day -1 (Check-in), Day 3 (Check-out), Day 8 (End of Study)/Early Termination Visit.

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day 1 Pre-dose, 1 hr, 2 hrs, 4 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 8 (End of Study)/Early termination Visit.

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day -1 (Check-in), Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 8 (End of Study)/Early Termination Visit.
Primary outcome [2] 331711 0
To determine the safety and tolerability of NIDO-361 when administered as multiple oral doses at escalating dose levels in healthy male subjects.

Safety Endpoints Include: Adverse Events (AEs), concomitant medications, physical examinations (including neurological examination, vital signs, weight, 12-lead ECG), and clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis).
Timepoint [2] 331711 0
Adverse Events: Assessed daily at Screening, Day -1 (Check-in), Day 1 to Day 8 (Treatment period), Day 9 (Check-out), Day 15 (End of Study)/Early Termination Visit. Adverse Events will be graded using The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will not be assessed daily from Days 9-14. Following Day 9 (Check-Out), participants will return to clinic on Day 15 and final study visit will be conducted, including review of any AEs participants may have experienced after being discharged from clinic on Day 9 (Check-Out).

Concomitant Medications: Assessed daily at Screening, Day -1 (Check-in), Day 1 to Day 8 (Treatment period), Day 9 (Check-out), Day 15 (End of Study)/Early Termination Visit. Site staff will question participants on use of concomitant medications at study visits.

Physical Examinations: General appearance; HEENT, neck (including thyroid and nodes); cardiovascular, respiratory, gastrointestinal, renal, neurological, and musculoskeletal systems; and skin will be assessed. Complete physical examination will be performed at Screening and Day 15 (End of Study)/Early Termination Visit. Symptom directed physical examination will be performed at Day -1 (Check-in) and Day 9 (Check-out).

Vital Signs: Blood pressure and heart rate are assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day -1 (Check-in), Day 1 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs and 8 hrs post-dose, Day 2 to Day 6: 6 hours post-dose, Day 7 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs 6hrs and 8 hrs post-dose, Day 8, Day 9 (Check-out), Day 15 (End of Study)/Early Termination Visit.

Weight: Assessed using scales at Screening, Day -1 (Check-in), Day 5 Pre-dose, Day 9 (Check-out), Day 15 (End of Study)/Early Termination Visit.

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day 1 Pre-dose, 1 hr, 2 hrs, 4 hrs post-dose, Day 2 Pre-dose, 24 hrs post-dose, Day 5 Pre-dose, Day 7 1 hr, 2 hr, 4 hrs post-dose, Day 9 (Check-out), Day 15 (End of Study)/Early Termination Visit.

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day -1 (Check-in), Day 2 pre-dose, Day 5 pre-dose, Day 8, Day 15 (End of Study)/Early Termination Visit.
Secondary outcome [1] 410610 0
To determine the Pharmacokinetics (PK) of NIDO-361 when administered as a single oral dose in healthy male subjects

Plasma concentrations and derived PK parameters of NIDO-361. AUClast, AUCtau, AUCinf, Cmax, Tmax, Cmin, t1/2 and other parameters will be derived and reported as appropriate
Timepoint [1] 410610 0
Plasma samples will be collected as follows:

Day 1 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post-dose
Day 2 24 hrs and 36 hrs post-dose
Day 3 48 hrs post-dose
Secondary outcome [2] 410838 0
To determine the PK of NIDO-361 when administered as multiple oral doses at escalating dose levels in healthy male subjects

Plasma concentrations and derived PK parameters of NIDO-361. AUClast, AUCtau, AUCinf, Cmax, Tmax, Cmin, t1/2 and other parameters will be derived and reported as appropriate
Timepoint [2] 410838 0
Plasma samples will be collected as follows:

Day 1 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post-dose
Day 2 24 hrs post-dose from Day 1
Day 7 Pre-dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs and 8 hrs post-dose
Day 8 24 hrs from the time of dosing on Day 7

Eligibility
Key inclusion criteria
To be included in this study, each individual must satisfy all the following criteria:
1. The subject is a healthy male adult, aged 18 to 55 years, inclusive, at the time of consent.
2. The subject weighs at least 45 kg (99 lb.) and has a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, at Screening.
3. In the opinion of the Investigator, the subject is capable of understanding and complying with protocol requirements.
4. The subject has documented ability to understand the written study informed consent form (ICF) and consent and has provided signed written informed consent prior to any study procedures.
5. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from the signing of the informed consent throughout the duration of the study and 90 days from the last dose. In addition, male subjects must be willing to forgo sperm donation for the duration of the study and 3 months after completion of the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
If an individual meets any of the following criteria, he is ineligible for this study:
1. Use of other investigational drugs within 30 days or 5 half-lives prior to the planned first drug administration, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
2. Clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, immunologic, malignant, metabolic, psychiatric, or other condition that, in the opinion of the Investigator, precludes the subject’s safe participation in the study or would interfere with the study assessments.
3. Malignancy or has received treatment for malignancy, other than treatment for basal cell or squamous cell carcinoma of the skin, within the previous 5 years.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The randomisation schedule will be generated by Sponsor or designee and will be provided to the site pharmacist prior to the start of this study. All randomisation data will be stored in a secured area, accessible only by authorised personnel.

A participants treatment assignment should remain blinded until the end of study. However, in the event of a medical emergency when the medical treatment of the participant depends on knowing the study treatment the participant received, the treatment blind may be broken. Access for emergency unblinding will be provided through code break envelopes provided to the site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Following confirmation of eligibility, participants will be randomly allocated to either active or placebo treatment at their Day 1 visit, in the SAD portion and the MAD portion of the study.
Permuted block randomisation will be implemented using SAS software.

Five randomisation lists will be created with 2 blocks of 2 and 6 subjects each (randomization ratio: 1:1, 1 active: 1 placebo for sentinels and randomization ratio of 5:1 5 active: 1 placebo for the remaining subjects), for each of the five SAD cohorts

Three randomisation lists will be created with 2 blocks of 4 subjects each (randomization ratio: 3:1, 6 active: 2 placebo), for each of the three MAD cohorts
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size was not calculated based on statistical hypothesis testing; however, the number of participants is sufficient for a Phase 1 assessment of safety, tolerability, and PK.

Primary (Safety) Analysis
Treatment Emergent Adverse Events (TEAEs) and Sudden Adverse Events (SAEs) assessed as related to study drug will be summarised for each dose group based on MedDRA (Version 25.0 or later) coding of verbatim terms reported by the investigators. Adverse Event (AE) incidence tables will be presented by system organ class and preferred term, the number and percentage of participants experiencing an AE, and the number and percentage of participants experiencing an AE by severity and by relationship to treatment.
Listings of all AEs, SAEs, deaths, and AEs leading to study discontinuation will be provided.
Summary statistics of vital signs, ECGs, clinical laboratory tests (hematology, chemistry and urinalysis) will be calculated by treatment group. Physical examination findings will be presented in data listings.

Secondary (PK) Analysis
For each part of the study, the concentrations of NIDO-361 in plasma will be summarised by Study Day, period (SAD/MAD), treatment, participant, visit/sampling timepoint and/or dose level over each scheduled sampling time using descriptive statistics as appropriate. Individual plasma concentration data versus time will be presented in data listings. Descriptive statistics, for example, N, arithmetic mean, standard deviation, median, minimum, and maximum, and percent coefficient of variation, will be used to summarize the plasma PK parameters for NIDO-361 by study day, period (SAD/MAD), treatment, visit/sampling timepoint, and/or dose level as appropriate. In addition, geometric mean and percent coefficient of variation may be computed for Cmax and AUCs. Dose proportionality will be tested for NIDO-361 Cmax and AUCs using a power model. For the SAD/MAD cohorts, the power model will be run after multiple dosing, and additional analysis will be included if appropriate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/08/2022
Actual
28/08/2022
Date of last participant enrolment
Anticipated
Actual
29/01/2023
Date of last data collection
Anticipated
Actual
3/03/2023
Sample size
Target
64
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22514 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 37755 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311604 0
Commercial sector/Industry
Name [1] 311604 0
Nido Biosciences, Inc.
Country [1] 311604 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Nido Biosciences, Inc.
Address
650 E. Kendall Street, 2nd Floor
Cambridge, Massachusetts 02142
United States of America
Country
United States of America
Secondary sponsor category [1] 313036 0
Commercial sector/Industry
Name [1] 313036 0
Avance Clinical Pty Ltd
Address [1] 313036 0
Level 1, 2 Ann Nelson Drive
Thebarton, SA 5031
Country [1] 313036 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311045 0
Bellberry Limited HREC
Ethics committee address [1] 311045 0
123 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 311045 0
Australia
Date submitted for ethics approval [1] 311045 0
08/06/2022
Approval date [1] 311045 0
14/07/2022
Ethics approval number [1] 311045 0
2022-05-566

Summary
Brief summary
This study will be investigating the safety and tolerability of NIDO-361 and the amount of NIDO-361 in the body when taken in single and multiple doses in healthy male participants so as to possibly be a treatment in the future for Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease. This is a condition that only affects men and causes muscle weakness, tremor, and cramps among other neuromuscular and hormonal symptoms. Kennedy’s Disease is caused by a genetic mutation affecting the androgen receptor, which controls how hormones like testosterone work in the body.
It is hoped that in patients with Kennedy’s Disease, NIDO-361 will correct the way the androgen receptor interprets signals from the testosterone re-establishing its normal function.

This study will involve the recruitment of 64 healthy male participants between the ages of 18 and 55 years who weigh at least 45kg and have a body mass index between 18-32 kg/m2. There will be 5 cohorts of 8 participating in the single ascending dose part of the study involving a 3 night in house stay and follow-up visit on Day 8 and 3 cohorts of 8 participating in the multiple ascending dose part of the study involving 7 days of consecutive dosing, a 9 night in house stay and follow-up visit on Day 15.
Trial website
Trial related presentations / publications
Public notes
Additional Key exclusion criteria:
Clinically significant acute illness, including coronavirus disease 2019 or persistent coronavirus disease 19 symptoms, in the 3 weeks prior to dosing, which in opinion of the Investigator, precludes the subject’s safe participation in the study or would interfere with the study assessments.

Contacts
Principal investigator
Name 119802 0
Dr Jonathan Newchurch
Address 119802 0
CMAX Clinical Research Pty Ltd
Level 5, 21-24 North Terrace
Adelaide
South Australia 5000
Country 119802 0
Australia
Phone 119802 0
+61 423 223 756
Fax 119802 0
Email 119802 0
jnewchurch@gmail.com
Contact person for public queries
Name 119803 0
Dr Jonathan Newchurch
Address 119803 0
CMAX Clinical Research Pty Ltd
Level 5, 21-24 North Terrace
Adelaide
South Australia 5000
Country 119803 0
Australia
Phone 119803 0
+61 423 223 756
Fax 119803 0
Email 119803 0
jnewchurch@gmail.com
Contact person for scientific queries
Name 119804 0
Dr Jonathan Newchurch
Address 119804 0
CMAX Clinical Research Pty Ltd
Level 5, 21-24 North Terrace
Adelaide
South Australia 5000
Country 119804 0
Australia
Phone 119804 0
+61 423 223 756
Fax 119804 0
Email 119804 0
jnewchurch@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and Intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.