Phase I BP Interferon (IFN) Beta-004

Browse trials for

• Multiple Sclerosis 3,460
• Multiple Sclerosis, Relapsing-Remitting 602

Multiple Sclerosis

3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.

This study's enrollment of 24 is below the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.

Lead sponsor

Centre Hospitalier Universitaire Vaudois is the lead sponsor of 203 studies on the registry; 47 are open to participants now.

Study arms

• Experimental
  Part A: Interferon beta-1a in HSA-free solution

  Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a without albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.

  Drug: Interferon beta-1a HSA-free biosimilar

• Experimental
  Part A: Interferon beta-1a combined with HSA+ solution

  Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.

  Drug: Interferon beta-1a HSA+ biosimilar

• Active comparator
  Part A: Interferon beta-1a in marketed HSA+ solution

  Twelve subjects will participate in 3 periods of part A, receiving 18 MIU original interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.

  Drug: Interferon beta-1a original

• Experimental
  Part B: Interferon beta-1a in HSA-free solution

  Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU biosimilar interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose \[i.e. dose 1 and 3\] and left side for even dose \[i.e. dose 2 and 4\]).

  Drug: Interferon beta-1a HSA-free biosimilar

• Active comparator
  Part B: Interferon beta-1a in marketed HSA+ solution

  Part B: Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU original interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose \[i.e. dose 1 and 3\] and left side for even dose \[i.e. dose 2 and 4\]).

  Drug: Interferon beta-1a original

Interventions

• DrugInterferon beta-1a HSA-free biosimilar

  6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution without albumin

  Also known as: Bioferon®

• DrugInterferon beta-1a HSA+ biosimilar

  6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution combined with albumin solution

  Also known as: Bioferon®

• DrugInterferon beta-1a original

  6 MIU/0.50 mL in pre-filled glass syringe solubilized in HSA and mannitol solution (marketed formulation)

  Also known as: Rebif®

Primary outcomes

1. Composite of interferon beta-1a PK parameters

   Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-inf\]) and maximum observed concentration (Cmax) following single dose administration, as well as time to Cmax (tmax; for s.c. injection) will be assessed. Mean residence time (MRT), half-life of elimination (t1/2), clearance (CL), and volume of distribution at steady-state (Vss) will be calculated.

   Time frame: Part A: 0, 2, 5, 10, 15, 20 [min post-dose] and 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-dose] / Part B: 0, 1, 2, 3, 4, 6, 12 [hours post-doses] and 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7)

Secondary outcomes

1. Serum concentration of neopterin (PD marker)

   Assessment by ELISA after i.v. and after s.c

   Time frame: Part A: 0, 6, 12, 24, 48, 72, 168 [hours post-doses] / Part B: 0, 6, 12 [hours post-doses] and 0, 6, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7)

2. Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability

   AE/SAE will be collected from the start of study treatment and until the follow-up visit

   Time frame: Up to Day 7

3. Composite of local reactions as a measure of local tolerance

   Any local symptoms rated as moderate (grade 3 for i.v. and 2 for s.c.) or severe (grade 4 and 5 for i.v.; grade 3 for s.c.) will be reported as an adverse event. The subjective painful sensation following injection of the drug will be assessed using a visual analogue scale (VAS)

   Time frame: Part A: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose] and longer if needed and until resolution in case of local reaction / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose] on Day 1 and 7, else daily up to Day 9 longer until resolution

4. Composite of clinical laboratory tests as a measure of safety and tolerability

   Clinical laboratory tests will include hematology, clinical chemistry and urinalysis

   Time frame: Screening and 0, 24 [hours post-doses]

5. Composite of vital signs as a measure of safety and tolerability

   Vital signs will include body temperature, blood pressure and heart rate

   Time frame: Part A: Screening and 0, 1, 2, 3, 4, 6, 8, 10, 12, 24 [hours post-dose] / Part B: Screening and 0, 1, 2, 3, 4, 6, 12 [hours post-doses], as well as 0, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-last dose] (Day 7)

6. Sickness behavior assessment

   Four parameters will be recorded (general feeling, headache, muscle ache, mood)

   Time frame: Part A: 0, 2, 4, 6, 8, 10, 12 [hours post-dose] / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose], as well as 24, 48, 72 [hours post-last dose] (Day 7)

7. Electrocardiogram (ECG) as a measure of safety and tolerability

   Twelve-lead ECG will be recorded

   Time frame: Screening and 0, 3 [hours post-dose]

Publications

• Perrottet N, Brunner-Ferber F, Grouzmann E, Spertini F, Biollaz J, Buclin T, Widmer N. Biases affecting injected doses of an experimental drug during clinical trials. Trials. 2016 Jul 16;17(1):321. doi: 10.1186/s13063-016-1463-5. PubMed 27423899 ↗