1. The results are in: now what?
Exploring implications for the field of the
delamanid phase III and STREAM stage 1
trial results
December 11, 2017
To view a live transcript of this webinar:

2. Webinar agenda Introduction– Erica Lessem, Treatment Action Group
Dr. Francesca Conradie, Wits University
Dr. Carole Diane Mitnick, Harvard Medical School
Marcus Low, Spotlight
Mandy Slutsker, ACTION
Q&A – please write in your questions in the “chat” feature

3. FIRST EVER MDR-TB CLINICAL TRIALS SUCCESSULLY CONDUCTED
THE TB NEWS
THE WORLD’S OLDEST INFECTIOUS DISEASE
October 2017
FIRST EVER MDR-TB CLINICAL TRIALS
SUCCESSULLY CONDUCTED
MDR-TB on the rise!
For decades, standards of care not based on RCT data
Two trials successfully built site and lab capacity, enrolled hundreds of patients, followed them up, did dozens of analyses…
and now we have the results!

4. What was the STREAM Stage 1 trial?
Randomized, controlled, open-label, non-inferiority trial
Evaluate the shorter regimen (also called “modified Bangladesh regimen,” recommended by WHO in advance of RCT data in 2016) vs the previous WHO standard of care (18-24 months)
Started July 2012, sponsored by the Union (USAID funding)

5. What was the DELAMANID C213 trial?
Randomized, placebo-controlled, double-masked, superiority trial
Primary endpoint = time to sputum culture conversion over 6 months
Evaluate adding delamanid vs placebo to the previous WHO standard of care (18-24 months)
Started September 2011, sponsored by Otsuka

6. efficacy results STREAM 1 Study arm (N) Control (N) Favorable
78.1% (164)
80.6% (87)
Unfavorable
21.9% (46)
19.4% (21)
95% Confidence Interval
-6.9%, 11.2%
C213*
Study arm (N)
Control (N)
Favorable
81.4% (276)
81.2% (138)
Unfavorable
18.5% (63)
18.8% (32)
Trial’s primary endpoint was time to sputum culture conversion by 6 mos: DLM arm had a 6 day shorter median (p=.0562)

7. Spoiler alert Neither trial demonstrated its primary hypothesis
BUT many “buts” –each intervention may still have utility
What does this mean for the field?

8. WHO policy plans: DELAMANID
WHO has concluded a rapid review of the delamanid phase III trial data
WHO is working on a formal Position Statement to be released in early January 2018
based on the Otsuka trial data (204 and 213) only
WHO has not received any observational data yet from implementers

9. WHO policy plans: SHORTER REGIMEN
Same process as for delamanid will be followed in January for the STREAM Stage 1 interim results
challenge: the trial follow-up has not concluded yet

10. WHO policy plans: Consolidated guidance
WHO will not attempt to consolidate October 2016 MDR-TB guidelines
Current data gaps
Burden on human/financial resources due to compliance with Guidelines Review Committee rules
Extensive review of WHO MDR-TB guidelines planned for Q3, 2018, once all necessary data are available, including:
final results for STREAM Stage 1,
observational data for delamanid,
observational data for bedaquiline,
systematic reviews on the use of the injectable drugs, and
detailed individual patent data (IPD) analyses to inform the possible regrouping of the second-line medicines used to treat MDR- and XDR-TB.